A Study of Abemaciclib (LY2835219) Alone or in Combination With Other Agents in Participants With Previously Treated Pancreatic Ductal Adenocarcinoma
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of abemaciclib alone and in combination with other drugs versus standard of care in participants with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Abemaciclib Abemaciclib given orally. |
Drug: Abemaciclib
Administered orally
Other Names:
|
Experimental: Abemaciclib + LY3023414 Abemaciclib given orally and LY3023414 given orally. |
Drug: Abemaciclib
Administered orally
Other Names:
Drug: LY3023414
Administered orally
|
Experimental: Standard of Care (Gemcitabine or Capecitabine) Gemcitabine given intravenously (IV) OR capecitabine given orally. |
Drug: Gemcitabine
Administered IV
Other Names:
Drug: Capecitabine
Administered orally
|
Outcome Measures
Primary Outcome Measures
- Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)]
Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
- Stage 2: Progression Free Survival (PFS) [Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months)]
PFS was defined as the time from the date of randomization until first observation of objective progressive disease as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a patient does not have a complete baseline disease assessment, then the PFS time will be censored at the randomization date, regardless of whether or not objectively determined disease progression or death has been observed for the patient; otherwise, if a patient is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time will be censored at the last complete objective progression-free disease assessment date.
Secondary Outcome Measures
- Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR [Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months)]
Objective response rate (ORR) is the percentage of participants with a BOR of CR or PR as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.
- Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) [Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose]
Mean steady state exposure was reported as measured by maximum observed plasma concentration (Cmax).
- Stage 1: PK: Area Under the Curve (AUC) (AUC[Tau]) of LY3023414 [Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)]
- Stage 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414 [Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)]
- Stage 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD [Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)]
- Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months [Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months)]
Clinical benefit rate (CBR) is the percentage of participants with a BOR of CR or PR, or SD ≥6 months. CR is defined as the disappearance of all target and non-target lesions & no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
- Stage 2: Duration of Response (DoR) [Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 6 Months)]
- Stage 2: Overall Survival (OS) [Baseline to Death from Any Cause (Up to 10 Months)]
OS duration is measured from the date of randomization to the date of death from any cause. for participants who is not known to have died as of the data-inclusion cutoff date, OS was censored at the last known alive date. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
- Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level [Baseline, 6 Months]
No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
- Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) [Baseline, 6 Months]
mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, and enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours, and typical completion time for this instrument is less than 5 minutes. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
- Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [Baseline, 6 Months]
The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much) Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
- Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414 [C2D1: 0h, C3D1: 0h, C4D1: 0h]
Mean steady state exposure was reported by trough pre-dose plasma concentrations.
- Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose [C1D1: 2h Post dose]
Mean single dose exposure was reported by plasma concentrations collected approximately 2 hours post-dose.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histological or cytological diagnosis of ductal adenocarcinoma of the pancreas.
-
Metastatic disease with documented disease progression following previous treatment with at least one, but no more than 2 prior therapies, with one of the prior therapies having been either gemcitabine-based or fluoropyrimidine-based therapy. Neoadjuvant and/or adjuvant therapies for localized resectable or unresectable PDAC each count as a line of therapy if multiagent chemotherapy regimens were administered (and neoadjuvant regimen was different than adjuvant regimen) and if the participant progressed with metastatic disease while taking or within 6 months of completion of (neo)adjuvant therapy.
-
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
-
Participant for whom treatment with monotherapy chemotherapy such as gemcitabine or capecitabine is a reasonable choice.
-
Discontinued all prior treatment for cancer at least 14 days prior to initial dose of study treatment.
-
Adequate organ function.
-
allow alanine aminotransferase (ALT) or aspartate aminotransferase (AST) up to 5x upper limit of normal (ULN) if liver metastases.
-
allow bilirubin up to 2.5 times ULN if elevation is not associated with other signs of liver toxicity or can be explained by mechanical obstruction - requires clinical research physician approval.
Exclusion Criteria:
-
Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: Participants with controlled atrial fibrillation for >30 days prior to study treatment initiation are eligible.
-
Have insulin-dependent diabetes mellitus. Participants with type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c (HbA1c) <7%.
-
Have symptomatic central nervous system metastasis. Screening of asymptomatic participants is not required for enrollment.
-
Have had major surgery within 7 days prior to initiation of study drug to allow for postoperative healing of the surgical wound and site(s).
-
Have previously received treatment with any cyclin-dependent kinase (CDK) 4 and 6 inhibitor or phosphatidylinositol 3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) inhibitor or have a known hypersensitivity to any component of the investigational products in this study.
-
Have a known hypersensitivity to investigator's choice of standard of care (gemcitabine or capecitabine).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Yale University School of Medicine | New Haven | Connecticut | United States | 06510 |
2 | Illinois CancerCare | Peoria | Illinois | United States | 61615 |
3 | Research Medical Center | Kansas City | Missouri | United States | 64132 |
4 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756-0001 |
5 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15232 |
6 | Sarah Cannon Cancer Center | Nashville | Tennessee | United States | 37203 |
7 | Tennessee Oncology PLLC | Nashville | Tennessee | United States | 37203 |
8 | Seattle Cancer Care Alliance | Olympia | Washington | United States | 98109 |
9 | Virginia Mason Medical Center | Seattle | Washington | United States | 98101 |
10 | University of Wisconsin-Madison Hospital and Health Clinic | Madison | Wisconsin | United States | 53792-4108 |
11 | For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. | Blacktown | Australia | 2148 | |
12 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Sydney | Australia | 2010 | |
13 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Brussels | Belgium | 1200 | |
14 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Edegem | Belgium | 2650 | |
15 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Leuven | Belgium | 3000 | |
16 | For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. | Wilrijk | Belgium | 2610 | |
17 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lyon | France | 69373 | |
18 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Paris | France | 75014 | |
19 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Pessac | France | 33604 | |
20 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Haifa | Israel | 3109601 | |
21 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ramat Gan | Israel | 5262000 | |
22 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tel Aviv | Israel | 6423906 | |
23 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Barcelona | Spain | 08036 | |
24 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hospitalet de Llobregat | Spain | 08908 | |
25 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Madrid | Spain | 28040 | |
26 | Fundacion Jimenez Diaz | Madrid | Spain | 28040 | |
27 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Malaga | Spain | 29010 | |
28 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tainan | Taiwan | 70403 | |
29 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Taipei city | Taiwan | 10048 | |
30 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Taipei | Taiwan | 11217 | |
31 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Taipei | Taiwan | ||
32 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | London | United Kingdom | NW1 2BU |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 16342
- I3Y-MC-JPCJ
- 2016-002218-36
Study Results
Participant Flow
Recruitment Details | Study was planned for stage 1 & stage 2. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. Completed participants are those who has CR, PR, SD, or PD and is off treatment. |
---|---|
Pre-assignment Detail | Per protocol, no efficacy analysis was planned for safety lead in. Purpose of safety lead in was only safety evaluation. All efficacy was done on randomized pts. |
Arm/Group Title | 150mg Abemaciclib + 150mg Galunisertib (Safety Lead-in) | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|---|
Arm/Group Description | Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle. | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Period Title: Overall Study | ||||
STARTED | 7 | 33 | 33 | 33 |
Received at Least One Dose of Study Drug | 7 | 32 | 33 | 26 |
COMPLETED | 7 | 22 | 20 | 19 |
NOT COMPLETED | 0 | 11 | 13 | 14 |
Baseline Characteristics
Arm/Group Title | 150mg Abemaciclib + 150mg Galunisertib (Safety Lead-in) | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine | Total |
---|---|---|---|---|---|
Arm/Group Description | Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle. | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. | Total of all reporting groups |
Overall Participants | 7 | 33 | 33 | 33 | 106 |
Age (years) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [years] |
65.29
(6.99)
|
61.09
(7.83)
|
62.52
(8.97)
|
66.85
(7.61)
|
63.40
(8.34)
|
Sex: Female, Male (Count of Participants) | |||||
Female |
4
57.1%
|
18
54.5%
|
16
48.5%
|
19
57.6%
|
57
53.8%
|
Male |
3
42.9%
|
15
45.5%
|
17
51.5%
|
14
42.4%
|
49
46.2%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||||
Hispanic or Latino |
0
0%
|
2
6.1%
|
4
12.1%
|
3
9.1%
|
9
8.5%
|
Not Hispanic or Latino |
7
100%
|
30
90.9%
|
28
84.8%
|
24
72.7%
|
89
84%
|
Unknown or Not Reported |
0
0%
|
1
3%
|
1
3%
|
6
18.2%
|
8
7.5%
|
Race (NIH/OMB) (Count of Participants) | |||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
7
21.2%
|
5
15.2%
|
4
12.1%
|
16
15.1%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
0%
|
1
3%
|
3
9.1%
|
4
3.8%
|
White |
7
100%
|
26
78.8%
|
26
78.8%
|
25
75.8%
|
84
79.2%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
1
3%
|
1
3%
|
2
1.9%
|
Region of Enrollment (Count of Participants) | |||||
Belgium |
0
0%
|
8
24.2%
|
6
18.2%
|
5
15.2%
|
19
17.9%
|
United States |
7
100%
|
8
24.2%
|
10
30.3%
|
8
24.2%
|
33
31.1%
|
Taiwan |
0
0%
|
7
21.2%
|
4
12.1%
|
3
9.1%
|
14
13.2%
|
United Kingdom |
0
0%
|
1
3%
|
0
0%
|
0
0%
|
1
0.9%
|
Israel |
0
0%
|
2
6.1%
|
4
12.1%
|
5
15.2%
|
11
10.4%
|
Australia |
0
0%
|
1
3%
|
1
3%
|
3
9.1%
|
5
4.7%
|
France |
0
0%
|
1
3%
|
1
3%
|
6
18.2%
|
8
7.5%
|
Spain |
0
0%
|
5
15.2%
|
7
21.2%
|
3
9.1%
|
15
14.2%
|
Outcome Measures
Title | Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) |
---|---|
Description | Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. |
Time Frame | Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months) |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 33 | 33 | 33 |
Number (95% Confidence Interval) [percentage of Participants] |
15.2
217.1%
|
12.1
36.7%
|
36.4
110.3%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0495 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0230 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments |
Title | Stage 2: Progression Free Survival (PFS) |
---|---|
Description | PFS was defined as the time from the date of randomization until first observation of objective progressive disease as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a patient does not have a complete baseline disease assessment, then the PFS time will be censored at the randomization date, regardless of whether or not objectively determined disease progression or death has been observed for the patient; otherwise, if a patient is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time will be censored at the last complete objective progression-free disease assessment date. |
Time Frame | Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months) |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants. Censored participants: Abemaciclib 200 mg: 3, Abemaciclib 150mg + LY3023414 150mg: 8, Gemcitabine & Capecitabine: 18; No participants were enrolled in stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled in stage 1. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 33 | 33 | 33 |
Median (95% Confidence Interval) [Months] |
1.68
|
1.81
|
3.25
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0085 |
Comments | ||
Method | Log Rank | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0123 |
Comments | ||
Method | Log Rank | |
Comments |
Title | Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR |
---|---|
Description | Objective response rate (ORR) is the percentage of participants with a BOR of CR or PR as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. |
Time Frame | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months) |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 33 | 33 | 33 |
Number (95% Confidence Interval) [percentage of Participants] |
3
42.9%
|
0
0%
|
3
9.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 1 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3017 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments |
Title | Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) |
---|---|
Description | Mean steady state exposure was reported as measured by maximum observed plasma concentration (Cmax). |
Time Frame | Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants who received at least one dose of Abemaciclib along with Galunisertib and had evaluable PK samples. |
Arm/Group Title | 150mg Abemaciclib + 150mg Galunisertib |
---|---|
Arm/Group Description | Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle. |
Measure Participants | 4 |
Abemaciclib |
356
(137)
|
LSN2839567 (M2) |
85.1
(66)
|
LSN3106726 (M20) |
153
(58)
|
Title | Stage 1: PK: Area Under the Curve (AUC) (AUC[Tau]) of LY3023414 |
---|---|
Description | |
Time Frame | Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles) |
Outcome Measure Data
Analysis Population Description |
---|
Zero Participants Analyzed: AUC cannot be calculated due to insufficient data collected. |
Arm/Group Title | 150mg Abemaciclib + 150mg LY3023414 |
---|---|
Arm/Group Description | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. |
Measure Participants | 0 |
Title | Stage 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414 |
---|---|
Description | |
Time Frame | Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles) |
Outcome Measure Data
Analysis Population Description |
---|
Zero Participants Analyzed: Cmax cannot be calculated due to insufficient data collected. |
Arm/Group Title | 150mg Abemaciclib + 150mg LY3023414 |
---|---|
Arm/Group Description | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. |
Measure Participants | 0 |
Title | Stage 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD |
---|---|
Description | |
Time Frame | Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months) |
Outcome Measure Data
Analysis Population Description |
---|
Data not reported, no patients were enrolled to stage 2. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 0 | 0 | 0 |
Title | Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months |
---|---|
Description | Clinical benefit rate (CBR) is the percentage of participants with a BOR of CR or PR, or SD ≥6 months. CR is defined as the disappearance of all target and non-target lesions & no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
Time Frame | Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months) |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 33 | 33 | 33 |
Number (95% Confidence Interval) [percentage of participants] |
3
42.9%
|
0
0%
|
3
9.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 1 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3017 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments |
Title | Stage 2: Duration of Response (DoR) |
---|---|
Description | |
Time Frame | Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 6 Months) |
Outcome Measure Data
Analysis Population Description |
---|
The population for analyzing DoR is the number of participants with response of CR or PR. There was only one participant in 200 mg Abemaciclib arm and one participant in Gemcitabine/Capecitabine arm. Due to small number of participants, the data is not analyzable using the planned time to event analysis. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 0 | 0 | 0 |
Title | Stage 2: Overall Survival (OS) |
---|---|
Description | OS duration is measured from the date of randomization to the date of death from any cause. for participants who is not known to have died as of the data-inclusion cutoff date, OS was censored at the last known alive date. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
Time Frame | Baseline to Death from Any Cause (Up to 10 Months) |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants. Censored participants: Abemaciclib 200mg: 11, Abemaciclib 150mg + LY3023414 150mg: 12, Gemcitabine + Capecitabine: 21; |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 33 | 33 | 33 |
Median (95% Confidence Interval) [Months] |
2.71
|
3.29
|
NA
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1938 |
Comments | ||
Method | Log Rank | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.600 | |
Confidence Interval |
(2-Sided) 95% 0.782 to 3.272 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2477 |
Comments | ||
Method | Log Rank | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.533 | |
Confidence Interval |
(2-Sided) 95% 0.746 to 3.150 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level |
---|---|
Description | No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
Time Frame | Baseline, 6 Months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants with baseline and post baseline CA 19-9 measurement. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 24 | 21 | 20 |
Mean (Standard Deviation) [U/mL] |
4281.53
(8177.89)
|
3225.29
(5730.25)
|
-501.17
(7198.70)
|
Title | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) |
---|---|
Description | mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, and enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours, and typical completion time for this instrument is less than 5 minutes. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
Time Frame | Baseline, 6 Months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants with baseline & post baseline value for the mBPI-sf specified item. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 19 | 14 | 13 |
Pain at its Worst in Last 24 hours |
0.63
(0.47)
|
-0.33
(0.55)
|
-0.02
(0.57)
|
Pain at its Least in Last 24 hours |
0.86
(0.42)
|
0.18
(0.49)
|
0.39
(0.51)
|
Pain on the Average |
0.62
(0.45)
|
-0.03
(0.51)
|
-0.07
(0.53)
|
Pain Right Now |
0.38
(0.34)
|
0.34
(0.59)
|
-0.38
(0.61)
|
Pain Interfered General Activity |
0.64
(0.47)
|
0.07
(0.55)
|
0.22
(0.57)
|
Pain Interfered with Mood |
0.54
(0.41)
|
0.28
(0.48)
|
0.60
(0.50)
|
Pain Interfered Walking Ability |
0.05
(0.55)
|
0.83
(0.64)
|
0.19
(0.67)
|
Pain Interfered with Normal Work |
1.07
(0.51)
|
0.66
(0.59)
|
0.19
(0.61)
|
Pain Interfered with Relations |
0.39
(0.52)
|
0.67
(0.61)
|
0.26
(0.63)
|
Pain Interfered with Sleep |
0.19
(0.53)
|
0.34
(0.61)
|
-0.56
(0.65)
|
Pain Interfered Enjoyment of Life |
0.69
(0.62)
|
0.39
(0.72)
|
-0.13
(0.75)
|
BPI Mean Pain Interference Score |
0.55
(0.44)
|
0.50
(0.51)
|
0.05
(0.54)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain at its Worst in Last 24 Hours | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.383 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.65 | |
Confidence Interval |
(2-Sided) 95% -0.84 to 2.13 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.74 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain at its Worst in Last 24 Hours | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.692 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -0.31 | |
Confidence Interval |
(2-Sided) 95% -1.91 to 1.28 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.79 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain at its Least in Last 24 Hours | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.469 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.48 | |
Confidence Interval |
(2-Sided) 95% -0.85 to 1.80 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain at its Least in Last 24 Hours | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.776 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -0.20 | |
Confidence Interval |
(2-Sided) 95% -1.62 to 1.22 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain on the Average | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.328 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.69 | |
Confidence Interval |
(2-Sided) 95% -0.72 to 2.11 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain on the Average | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.954 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.04 | |
Confidence Interval |
(2-Sided) 95% -1.45 to 1.54 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.74 |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Right Now | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.350 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.75 | |
Confidence Interval |
(2-Sided) 95% -0.85 to 2.36 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.80 |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain right now. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.405 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.72 | |
Confidence Interval |
(2-Sided) 95% -1.01 to 2.44 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.85 |
|
Estimation Comments |
Statistical Analysis 9
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered General Activity | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.565 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.43 | |
Confidence Interval |
(2-Sided) 95% -1.06 to 1.91 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
Estimation Comments |
Statistical Analysis 10
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered General Activity | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.848 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -0.15 | |
Confidence Interval |
(2-Sided) 95% -1.74 to 1.43 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.79 |
|
Estimation Comments |
Statistical Analysis 11
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered with Mood | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.928 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -0.06 | |
Confidence Interval |
(2-Sided) 95% -1.37 to 1.25 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
Estimation Comments |
Statistical Analysis 12
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered with Mood | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.650 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -0.32 | |
Confidence Interval |
(2-Sided) 95% -1.71 to 1.08 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
Estimation Comments |
Statistical Analysis 13
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered Walking Ability | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.865 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -0.15 | |
Confidence Interval |
(2-Sided) 95% -1.89 to 1.60 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.86 |
|
Estimation Comments |
Statistical Analysis 14
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered Walking Ability | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.497 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.63 | |
Confidence Interval |
(2-Sided) 95% -1.23 to 2.50 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.92 |
|
Estimation Comments |
Statistical Analysis 15
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered with Normal Work | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.272 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.89 | |
Confidence Interval |
(2-Sided) 95% -0.72 to 2.50 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.80 |
|
Estimation Comments |
Statistical Analysis 16
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered with Normal Work | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.583 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.47 | |
Confidence Interval |
(2-Sided) 95% -1.25 to 2.19 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.85 |
|
Estimation Comments |
Statistical Analysis 17
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered with Relations | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.876 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.13 | |
Confidence Interval |
(2-Sided) 95% -1.53 to 1.79 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.82 |
|
Estimation Comments |
Statistical Analysis 18
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered with relations. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.644 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.41 | |
Confidence Interval |
(2-Sided) 95% -1.37 to 2.19 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.88 |
|
Estimation Comments |
Statistical Analysis 19
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered with Sleep | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.384 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.75 | |
Confidence Interval |
(2-Sided) 95% -0.97 to 2.48 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.85 |
|
Estimation Comments |
Statistical Analysis 20
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.318 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.90 | |
Confidence Interval |
(2-Sided) 95% -0.90 to 2.71 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.89 |
|
Estimation Comments |
Statistical Analysis 21
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered Enjoyment of Life | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.407 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.81 | |
Confidence Interval |
(2-Sided) 95% -1.15 to 2.78 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.97 |
|
Estimation Comments |
Statistical Analysis 22
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Pain Interfered Enjoyment of Life | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.620 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.52 | |
Confidence Interval |
(2-Sided) 95% -1.58 to 2.62 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.04 |
|
Estimation Comments |
Statistical Analysis 23
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | BPI-Mean Interference Score | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.475 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.50 | |
Confidence Interval |
(2-Sided) 95% -0.90 to 1.91 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
Estimation Comments |
Statistical Analysis 24
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | BPI-Mean Interference Score | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.540 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.46 | |
Confidence Interval |
(2-Sided) 95% -1.04 to 1.96 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.74 |
|
Estimation Comments |
Title | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) |
---|---|
Description | The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much) Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
Time Frame | Baseline, 6 Months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants with baseline & post baseline value for the EORTC QLQ-C30 specified item. |
Arm/Group Title | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine |
---|---|---|---|
Arm/Group Description | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. |
Measure Participants | 19 | 14 | 14 |
Global Health Status |
-6.21
(3.87)
|
-4.82
(4.50)
|
-2.40
(4.64)
|
Functional Scales: Physical Functioning |
-14.44
(4.40)
|
-11.65
(5.12)
|
-5.42
(5.12)
|
Functional Scales: Role Functioning |
-17.09
(6.17)
|
-18.05
(7.32)
|
-17.10
(7.36)
|
Functional Scales: Emotional Functioning |
-4.89
(4.49)
|
-0.63
(5.22)
|
2.06
(5.41)
|
Functional Scales: Cognitive Functioning |
-10.43
(4.10)
|
-8.39
(4.77)
|
-5.18
(4.95)
|
Functional Scale: Social Functioning |
-21.12
(4.90)
|
-17.09
(5.72)
|
-2.00
(5.95)
|
Symptom Scales: Fatigue |
14.13
(4.92)
|
14.90
(5.73)
|
5.64
(5.71)
|
Symptom Scales: Nausea and Vomiting |
7.98
(5.57)
|
9.42
(6.47)
|
11.88
(6.50)
|
Symptom Scales: Pain |
9.79
(5.63)
|
2.68
(6.61)
|
5.43
(6.62)
|
Symptom Scale: Dysopnea |
0.35
(5.48)
|
11.19
(6.38)
|
-4.51
(6.36)
|
Symptom Scale: Insomnia |
-5.19
(5.17)
|
1.83
(6.01)
|
-6.71
(6.05)
|
Symptom Scale: Appetite Loss |
12.54
(5.79)
|
15.32
(6.77)
|
9.51
(7.30)
|
Symptom Scale: Constipation |
2.96
(5.95)
|
-6.51
(6.96)
|
12.93
(7.15)
|
Symptom Scale: Diarrhoea |
15.71
(6.76)
|
26.28
(7.83)
|
20.51
(7.98)
|
Symptom Scale: Financial difficulties |
3.96
(4.82)
|
2.45
(5.68)
|
-3.30
(5.87)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Global health status | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.818 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -1.39 | |
Confidence Interval |
(2-Sided) 95% -13.46 to 10.68 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.98 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Global health status | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.533 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -3.80 | |
Confidence Interval |
(2-Sided) 95% -16.03 to 8.42 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.06 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Physical functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.681 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -2.79 | |
Confidence Interval |
(2-Sided) 95% -16.40 to 10.82 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.75 |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Physical functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.189 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -9.02 | |
Confidence Interval |
(2-Sided) 95% -22.63 to 4.59 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.75 |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Role functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.921 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 95% -18.29 to 20.21 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.54 |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Role functioning. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.999 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 0.01 | |
Confidence Interval |
(2-Sided) 95% -19.40 to 19.42 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.62 |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Emotional functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.541 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -4.26 | |
Confidence Interval |
(2-Sided) 95% -18.20 to 9.68 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.91 |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Emotional functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.330 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -6.95 | |
Confidence Interval |
(2-Sided) 95% -21.17 to 7.27 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.05 |
|
Estimation Comments |
Statistical Analysis 9
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Cognitive Functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.747 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -2.04 | |
Confidence Interval |
(2-Sided) 95% -14.74 to 10.66 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.29 |
|
Estimation Comments |
Statistical Analysis 10
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Cognitive functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.419 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -5.25 | |
Confidence Interval |
(2-Sided) 95% -18.22 to 7.73 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.43 |
|
Estimation Comments |
Statistical Analysis 11
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Social functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.596 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -4.02 | |
Confidence Interval |
(2-Sided) 95% -19.23 to 11.19 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.53 |
|
Estimation Comments |
Statistical Analysis 12
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Functional Scales: Social functioning | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.017 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -19.12 | |
Confidence Interval |
(2-Sided) 95% -34.68 to -3.55 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.71 |
|
Estimation Comments |
Statistical Analysis 13
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptoms Scales: Fatigue | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.919 |
Comments | Social Scales: Fatigue | |
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -0.77 | |
Confidence Interval |
(2-Sided) 95% -16.03 to 14.49 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.57 |
|
Estimation Comments |
Statistical Analysis 14
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Fatigue | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.267 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 8.48 | |
Confidence Interval |
(2-Sided) 95% -6.72 to 23.69 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.54 |
|
Estimation Comments |
Statistical Analysis 15
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Nausea and Vomiting | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.866 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -1.45 | |
Confidence Interval |
(2-Sided) 95% -18.66 to 15.77 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.54 |
|
Estimation Comments |
Statistical Analysis 16
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Nausea and Vomiting | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.652 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -3.90 | |
Confidence Interval |
(2-Sided) 95% -21.23 to 13.43 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.59 |
|
Estimation Comments |
Statistical Analysis 17
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Pain | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.417 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 7.11 | |
Confidence Interval |
(2-Sided) 95% -10.39 to 24.60 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.67 |
|
Estimation Comments |
Statistical Analysis 18
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Pain | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.618 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 4.36 | |
Confidence Interval |
(2-Sided) 95% -13.16 to 21.89 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.69 |
|
Estimation Comments |
Statistical Analysis 19
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Dyspnoea | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.206 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -10.84 | |
Confidence Interval |
(2-Sided) 95% -27.85 to 6.18 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.44 |
|
Estimation Comments |
Statistical Analysis 20
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Dyspnoea | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.566 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 4.86 | |
Confidence Interval |
(2-Sided) 95% -12.08 to 21.80 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.40 |
|
Estimation Comments |
Statistical Analysis 21
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Insomnia | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.380 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -7.02 | |
Confidence Interval |
(2-Sided) 95% -23.01 to 8.96 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.93 |
|
Estimation Comments |
Statistical Analysis 22
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Insomnia | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.850 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 1.52 | |
Confidence Interval |
(2-Sided) 95% -14.60 to 17.64 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.99 |
|
Estimation Comments |
Statistical Analysis 23
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Appetite loss | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.756 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -2.79 | |
Confidence Interval |
(2-Sided) 95% -20.78 to 15.21 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 8.91 |
|
Estimation Comments |
Statistical Analysis 24
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Appetite loss | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.747 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 3.02 | |
Confidence Interval |
(2-Sided) 95% -15.77 to 21.82 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.31 |
|
Estimation Comments |
Statistical Analysis 25
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Constipation | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.311 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 9.47 | |
Confidence Interval |
(2-Sided) 95% -9.16 to 28.09 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.23 |
|
Estimation Comments |
Statistical Analysis 26
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Constipation | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.290 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -9.97 | |
Confidence Interval |
(2-Sided) 95% -28.75 to 8.80 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.30 |
|
Estimation Comments |
Statistical Analysis 27
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Diarrhoea | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.323 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -10.57 | |
Confidence Interval |
(2-Sided) 95% -31.93 to 10.78 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 10.58 |
|
Estimation Comments |
Statistical Analysis 28
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Diarrhoea | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.651 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | -4.80 | |
Confidence Interval |
(2-Sided) 95% -26.08 to 16.48 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 10.54 |
|
Estimation Comments |
Statistical Analysis 29
Statistical Analysis Overview | Comparison Group Selection | 200mg Abemaciclib, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Financial Difficulties | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.841 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 1.51 | |
Confidence Interval |
(2-Sided) 95% -13.57 to 16.59 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.47 |
|
Estimation Comments |
Statistical Analysis 30
Statistical Analysis Overview | Comparison Group Selection | 150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine |
---|---|---|
Comments | Symptom Scales: Financial Difficulties | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.344 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | LSMean Difference |
Estimated Value | 7.26 | |
Confidence Interval |
(2-Sided) 95% -8.03 to 22.54 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.57 |
|
Estimation Comments |
Title | Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414 |
---|---|
Description | Mean steady state exposure was reported by trough pre-dose plasma concentrations. |
Time Frame | C2D1: 0h, C3D1: 0h, C4D1: 0h |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants who received at least one dose of 150mg LY3023414 and had evaluable PK samples. |
Arm/Group Title | 150mg Abemaciclib + 150mg LY3023414 |
---|---|
Arm/Group Description | Participants received oral dose of 150mg Abemaciclib twice daily along with 150mg LY3023414 twice daily for 28 day cycles. |
Measure Participants | 9 |
Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
27.3
(450)
|
Title | Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose |
---|---|
Description | Mean single dose exposure was reported by plasma concentrations collected approximately 2 hours post-dose. |
Time Frame | C1D1: 2h Post dose |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants who received at least one dose of 150mg LY3023414 and had evaluable PK samples. |
Arm/Group Title | 150mg Abemaciclib + 150mg LY3023414 |
---|---|
Arm/Group Description | Participants received oral dose of 150mg Abemaciclib twice daily along with 150mg LY3023414 twice daily for 28 day cycles. |
Measure Participants | 28 |
Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
518
(67)
|
Adverse Events
Time Frame | Up to 30 weeks | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly. | |||||||
Arm/Group Title | 150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In) | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine | ||||
Arm/Group Description | Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle. | Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. | ||||
All Cause Mortality |
||||||||
150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In) | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/7 (71.4%) | 22/32 (68.8%) | 21/33 (63.6%) | 12/26 (46.2%) | ||||
Serious Adverse Events |
||||||||
150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In) | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/7 (57.1%) | 17/32 (53.1%) | 18/33 (54.5%) | 15/26 (57.7%) | ||||
Blood and lymphatic system disorders | ||||||||
Anaemia | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Febrile neutropenia | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Neutropenia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Thrombocytopenia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 2/33 (6.1%) | 8 | 0/26 (0%) | 0 |
Gastrointestinal disorders | ||||||||
Abdominal pain | 0/7 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Ascites | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Diarrhoea | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Duodenal stenosis | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Gastric ulcer haemorrhage | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Gastrointestinal perforation | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Intestinal obstruction | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Large intestinal obstruction | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Nausea | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Obstruction gastric | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Oesophagitis | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Stomatitis | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 2/33 (6.1%) | 2 | 1/26 (3.8%) | 1 |
Subileus | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Vomiting | 0/7 (0%) | 0 | 1/32 (3.1%) | 2 | 2/33 (6.1%) | 2 | 4/26 (15.4%) | 4 |
General disorders | ||||||||
Asthenia | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Chills | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Fatigue | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
General physical health deterioration | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Malaise | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Multiple organ dysfunction syndrome | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Pyrexia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 2/33 (6.1%) | 3 | 0/26 (0%) | 0 |
Systemic inflammatory response syndrome | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Hepatobiliary disorders | ||||||||
Bile duct obstruction | 0/7 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Cholangitis | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 2 | 1/26 (3.8%) | 1 |
Cholangitis acute | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 2 |
Infections and infestations | ||||||||
Abdominal infection | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 2 | 0/26 (0%) | 0 |
Bacteraemia | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Escherichia bacteraemia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Peritonitis bacterial | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Sepsis | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 2 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Upper respiratory tract infection | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Urosepsis | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Investigations | ||||||||
Blood creatinine increased | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Platelet count decreased | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
White blood cell count decreased | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||
Acidosis | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Decreased appetite | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Dehydration | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Failure to thrive | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Hypokalaemia | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Hyponatraemia | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Hypophosphataemia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Tumour lysis syndrome | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||
Back pain | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Muscular weakness | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Tumour pain | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Nervous system disorders | ||||||||
Cerebrovascular accident | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 2 | 0/26 (0%) | 0 |
Ischaemic cerebral infarction | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Psychiatric disorders | ||||||||
Confusional state | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Mental status changes | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Renal and urinary disorders | ||||||||
Acute kidney injury | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Hypoxia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Pleural effusion | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Pulmonary embolism | 1/7 (14.3%) | 1 | 2/32 (6.3%) | 2 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Respiratory failure | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Vascular disorders | ||||||||
Deep vein thrombosis | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Embolism | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Hypotension | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In) | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | Gemcitabine or Capecitabine | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 7/7 (100%) | 30/32 (93.8%) | 33/33 (100%) | 25/26 (96.2%) | ||||
Blood and lymphatic system disorders | ||||||||
Anaemia | 3/7 (42.9%) | 14 | 10/32 (31.3%) | 18 | 6/33 (18.2%) | 7 | 11/26 (42.3%) | 19 |
Cytopenia | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Leukopenia | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Neutropenia | 2/7 (28.6%) | 2 | 4/32 (12.5%) | 9 | 0/33 (0%) | 0 | 2/26 (7.7%) | 5 |
Thrombocytopenia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 5/33 (15.2%) | 5 | 4/26 (15.4%) | 17 |
Cardiac disorders | ||||||||
Tachycardia | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Endocrine disorders | ||||||||
Hypothyroidism | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Eye disorders | ||||||||
Photopsia | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Visual impairment | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Gastrointestinal disorders | ||||||||
Abdominal discomfort | 2/7 (28.6%) | 2 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Abdominal distension | 1/7 (14.3%) | 2 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Abdominal pain | 1/7 (14.3%) | 1 | 7/32 (21.9%) | 8 | 5/33 (15.2%) | 5 | 6/26 (23.1%) | 8 |
Abdominal pain upper | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 4/26 (15.4%) | 4 |
Ascites | 0/7 (0%) | 0 | 4/32 (12.5%) | 5 | 2/33 (6.1%) | 2 | 3/26 (11.5%) | 3 |
Constipation | 1/7 (14.3%) | 2 | 5/32 (15.6%) | 6 | 2/33 (6.1%) | 2 | 7/26 (26.9%) | 7 |
Diarrhoea | 4/7 (57.1%) | 4 | 12/32 (37.5%) | 21 | 17/33 (51.5%) | 19 | 8/26 (30.8%) | 16 |
Dry mouth | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 2/33 (6.1%) | 2 | 0/26 (0%) | 0 |
Dyspepsia | 0/7 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Eructation | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Flatulence | 0/7 (0%) | 0 | 2/32 (6.3%) | 2 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Gastrointestinal pain | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Nausea | 5/7 (71.4%) | 5 | 9/32 (28.1%) | 14 | 15/33 (45.5%) | 18 | 9/26 (34.6%) | 10 |
Stomatitis | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 12/33 (36.4%) | 16 | 6/26 (23.1%) | 9 |
Vomiting | 2/7 (28.6%) | 3 | 10/32 (31.3%) | 12 | 15/33 (45.5%) | 22 | 6/26 (23.1%) | 8 |
General disorders | ||||||||
Asthenia | 1/7 (14.3%) | 1 | 4/32 (12.5%) | 5 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Chills | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 2 | 0/26 (0%) | 0 |
Fatigue | 4/7 (57.1%) | 7 | 16/32 (50%) | 22 | 17/33 (51.5%) | 25 | 11/26 (42.3%) | 12 |
Feeling cold | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
General physical health deterioration | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 3 | 3/26 (11.5%) | 3 |
Malaise | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Non-cardiac chest pain | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/26 (7.7%) | 2 |
Oedema | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Oedema peripheral | 2/7 (28.6%) | 2 | 4/32 (12.5%) | 4 | 5/33 (15.2%) | 6 | 1/26 (3.8%) | 1 |
Peripheral swelling | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Pyrexia | 2/7 (28.6%) | 2 | 3/32 (9.4%) | 5 | 5/33 (15.2%) | 6 | 0/26 (0%) | 0 |
Hepatobiliary disorders | ||||||||
Bile duct obstruction | 0/7 (0%) | 0 | 4/32 (12.5%) | 4 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Infections and infestations | ||||||||
Bacterial sepsis | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Upper respiratory tract infection | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/26 (7.7%) | 2 |
Urinary tract infection | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Injury, poisoning and procedural complications | ||||||||
Fall | 0/7 (0%) | 0 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 2 | 0/26 (0%) | 0 |
Investigations | ||||||||
Alanine aminotransferase increased | 1/7 (14.3%) | 1 | 4/32 (12.5%) | 8 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Aspartate aminotransferase increased | 2/7 (28.6%) | 3 | 3/32 (9.4%) | 6 | 0/33 (0%) | 0 | 1/26 (3.8%) | 3 |
Blood alkaline phosphatase increased | 1/7 (14.3%) | 1 | 5/32 (15.6%) | 9 | 3/33 (9.1%) | 5 | 1/26 (3.8%) | 1 |
Blood bilirubin increased | 0/7 (0%) | 0 | 5/32 (15.6%) | 16 | 1/33 (3%) | 1 | 1/26 (3.8%) | 2 |
Blood creatinine increased | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 2 | 3/33 (9.1%) | 5 | 1/26 (3.8%) | 3 |
Blood potassium decreased | 0/7 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Blood sodium decreased | 0/7 (0%) | 0 | 2/32 (6.3%) | 3 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
International normalised ratio increased | 0/7 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Lymphocyte count decreased | 0/7 (0%) | 0 | 2/32 (6.3%) | 3 | 0/33 (0%) | 0 | 2/26 (7.7%) | 4 |
Neutrophil count decreased | 0/7 (0%) | 0 | 4/32 (12.5%) | 7 | 1/33 (3%) | 3 | 2/26 (7.7%) | 8 |
Occult blood positive | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Platelet count decreased | 0/7 (0%) | 0 | 10/32 (31.3%) | 20 | 5/33 (15.2%) | 11 | 4/26 (15.4%) | 9 |
Weight decreased | 2/7 (28.6%) | 2 | 0/32 (0%) | 0 | 3/33 (9.1%) | 3 | 1/26 (3.8%) | 1 |
White blood cell count decreased | 2/7 (28.6%) | 3 | 4/32 (12.5%) | 4 | 1/33 (3%) | 3 | 3/26 (11.5%) | 5 |
Metabolism and nutrition disorders | ||||||||
Decreased appetite | 3/7 (42.9%) | 4 | 9/32 (28.1%) | 11 | 8/33 (24.2%) | 9 | 8/26 (30.8%) | 8 |
Dehydration | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 2/33 (6.1%) | 2 | 1/26 (3.8%) | 1 |
Failure to thrive | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Fluid retention | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Hyperglycaemia | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 3/33 (9.1%) | 5 | 1/26 (3.8%) | 1 |
Hyperkalaemia | 0/7 (0%) | 0 | 1/32 (3.1%) | 2 | 2/33 (6.1%) | 2 | 2/26 (7.7%) | 2 |
Hypoalbuminaemia | 2/7 (28.6%) | 5 | 1/32 (3.1%) | 1 | 3/33 (9.1%) | 3 | 1/26 (3.8%) | 1 |
Hypocalcaemia | 1/7 (14.3%) | 2 | 1/32 (3.1%) | 4 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Hypokalaemia | 0/7 (0%) | 0 | 3/32 (9.4%) | 4 | 3/33 (9.1%) | 3 | 4/26 (15.4%) | 5 |
Hypomagnesaemia | 1/7 (14.3%) | 1 | 3/32 (9.4%) | 3 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Hyponatraemia | 4/7 (57.1%) | 6 | 1/32 (3.1%) | 1 | 3/33 (9.1%) | 6 | 1/26 (3.8%) | 1 |
Hypophagia | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Hypophosphataemia | 0/7 (0%) | 0 | 2/32 (6.3%) | 3 | 1/33 (3%) | 2 | 1/26 (3.8%) | 1 |
Musculoskeletal and connective tissue disorders | ||||||||
Arthropathy | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Back pain | 1/7 (14.3%) | 1 | 3/32 (9.4%) | 3 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Flank pain | 1/7 (14.3%) | 2 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Muscular weakness | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 2/33 (6.1%) | 3 | 0/26 (0%) | 0 |
Musculoskeletal pain | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Myalgia | 0/7 (0%) | 0 | 2/32 (6.3%) | 3 | 1/33 (3%) | 2 | 0/26 (0%) | 0 |
Pain in extremity | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Tumour pain | 0/7 (0%) | 0 | 2/32 (6.3%) | 3 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Nervous system disorders | ||||||||
Dizziness | 2/7 (28.6%) | 2 | 1/32 (3.1%) | 1 | 3/33 (9.1%) | 3 | 0/26 (0%) | 0 |
Dysgeusia | 0/7 (0%) | 0 | 3/32 (9.4%) | 3 | 4/33 (12.1%) | 4 | 0/26 (0%) | 0 |
Psychiatric disorders | ||||||||
Anxiety | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Confusional state | 0/7 (0%) | 0 | 3/32 (9.4%) | 3 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Depression | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Insomnia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 2/33 (6.1%) | 3 | 0/26 (0%) | 0 |
Renal and urinary disorders | ||||||||
Acute kidney injury | 0/7 (0%) | 0 | 1/32 (3.1%) | 2 | 0/33 (0%) | 0 | 3/26 (11.5%) | 3 |
Haematuria | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Hydronephrosis | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Reproductive system and breast disorders | ||||||||
Prostatomegaly | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/17 (5.9%) | 1 | 0/10 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Atelectasis | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Cough | 1/7 (14.3%) | 1 | 2/32 (6.3%) | 2 | 2/33 (6.1%) | 2 | 2/26 (7.7%) | 2 |
Dysphonia | 1/7 (14.3%) | 2 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/26 (3.8%) | 1 |
Dyspnoea | 2/7 (28.6%) | 2 | 2/32 (6.3%) | 2 | 4/33 (12.1%) | 5 | 3/26 (11.5%) | 5 |
Hypoxia | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 2/33 (6.1%) | 2 | 0/26 (0%) | 0 |
Pleural effusion | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 2/33 (6.1%) | 2 | 1/26 (3.8%) | 1 |
Pneumothorax | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/26 (7.7%) | 4 |
Upper-airway cough syndrome | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||
Dry skin | 1/7 (14.3%) | 1 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 1/26 (3.8%) | 1 |
Ecchymosis | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Palmar-plantar erythrodysaesthesia syndrome | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 2/33 (6.1%) | 2 | 10/26 (38.5%) | 24 |
Pruritus | 2/7 (28.6%) | 2 | 2/32 (6.3%) | 2 | 2/33 (6.1%) | 2 | 1/26 (3.8%) | 1 |
Rash | 2/7 (28.6%) | 3 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Rash maculo-papular | 0/7 (0%) | 0 | 1/32 (3.1%) | 3 | 3/33 (9.1%) | 3 | 1/26 (3.8%) | 1 |
Skin discolouration | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Skin ulcer | 0/7 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/26 (7.7%) | 2 |
Vascular disorders | ||||||||
Hot flush | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Hypotension | 1/7 (14.3%) | 1 | 3/32 (9.4%) | 3 | 1/33 (3%) | 1 | 0/26 (0%) | 0 |
Peripheral coldness | 1/7 (14.3%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/26 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Chief Medical Officer |
---|---|
Organization | Eli Lilly and Company |
Phone | 800-545-5979 |
ClinicalTrials.gov@lilly.com |
- 16342
- I3Y-MC-JPCJ
- 2016-002218-36