A Study of LY2510924 and Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Study Details
Study Description
Brief Summary
To compare the progression free survival of LY2510924 plus sunitinib therapy versus sunitinib in the first-line setting for patients with metastatic clear-cell renal cell carcinoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY2510924 + Sunitinib LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
Drug: LY2510924
Administered subcutaneously
Drug: Sunitinib
Administered orally
|
| Active Comparator: Sunitinib 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
Drug: Sunitinib
Administered orally
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [Randomization to Measured Progressive Disease or Date of Death From Any Cause (Up to 67 Months)]
PFS is defined as the time from date of study Randomization to the first date of objectively determined progressive disease(PD) or death from any cause defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0).PD was defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study(including the baseline sum if that is the smallest).In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions was also considered PD.For participants still alive at the time of analysis and without evidence of tumor progression,PFS would be censored at the date of the most recent objective progression-free observation.For participants who receive subsequent anticancer therapy prior to objective disease progression or death,PFS was censored at the date of the last objective progression-free observation prior to the date of subsequent therapy.
Secondary Outcome Measures
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR]) [Baseline to Date of Tumor Response or Measured Progressive Disease or Date of Death from any Cause ((Up to 67 Months)]
ORR is defined as the number of participants with a best response of CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.
- Overall Survival (OS) [Randomization to Date of Death from Any Cause (Up to 67 Months)]
OS is defined as the time from the date of study randomization to the date of death from any cause. For participants who were still alive as of the data cut-off date, OS time will be censored on the date of the participant's last contact (last contact for participants in post-discontinuation = last known alive date in mortality status).
- Duration of Overall Response (DOR) [Date of First Response to Date of Progressive Disease (Up to 67 Months)]
DOR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
- Duration of Complete Response [Date of Complete Response to the Date of Progressive Disease (Up to 67 Months)]
Duration of complete response is defined as the time from the date when the measurement criteria are met for complete response until the date of first observation of objective disease progression (taking as reference for PD the smallest measurements recorded since the treatment started). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Evidence of histologically confirmed renal cell carcinoma (RCC) with metastases with a component of clear (conventional) cell histology
-
A diagnosis of metastatic renal cell carcinoma (RCC) and have not received prior treatment with systemic (adjuvant or neoadjuvant) therapy for renal cell carcinoma (RCC) (including targeted therapy such as tyrosine kinase inhibitors or bevacizumab, immunotherapy, chemotherapy, hormonal, or investigational therapy)
-
Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Computed tomography (CT) or magnetic resonance imaging (MRI) should be performed within 4 weeks prior to study entry
-
Participants who have or have not had their primary tumor removed by nephrectomy are allowed. Participants who have not had a nephrectomy should not be considered to need a nephrectomy as part of their overall therapy at the time of enrollment
-
Performance status score of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
-
Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements, to be conducted within seven days prior to treatment: (upper limit of normal/lower limit of normal [ULN/LLN])
-
hemoglobin (greater than) >8.0 g/dL (grams per deciliter)
-
absolute neutrophil count (ANC) (greater than or equal to) ≥1.5 × 10^9/L (liter)
-
platelet count (greater than or equal to) ≥100 × 10^9/L (liter)
-
total bilirubin (less than or equal to) ≤ 1.5 × ULN (upper limit of normal)
-
serum creatinine (less than or equal to) ≤2 × ULN (upper limit of normal)
-
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (less than or equal to) ≤2.5 × ULN (upper limits of normal) [or (less than or equal to) ≤5 × ULN (upper limits of normal) for patients with liver involvement of their cancer]
-
Prothrombin Time (PT) or International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT) (less than or equal to) ≤1.5 x ULN (upper limit of normal)
-
For women: Must be surgically sterile (surgical procedure: bilateral tubal ligation, hysterectomy, bilateral oophorectomy), post-menopausal (at least 12 consecutive months of amenorrhea), or have a negative pregnancy test. Women of childbearing potential should be compliant with a medically approved contraceptive regimen (intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after the treatment period; must have a negative serum pregnancy test within 7 days before study enrollment, and must not be breastfeeding
-
For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after the treatment period
-
Estimated life expectancy of at least 12 weeks
-
Provide written informed consent/assent prior to any study-specific procedures
-
No prior malignancies with the exception of stage 1 cancers definitively treated, carcinoma in situ (any primary site), treated non-melanoma skin cancer, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated 5 or more years prior to study entry
-
Capable and willing to learn to self-administer LY2510924, or have a caregiver who is willing to learn and able to administer LY2510924 by subcutaneous (SC) injection and are able to swallow tablets
-
Left ventricular ejection fraction (LVEF) greater than or equal to LLN as defined by the institution performing the scan, as assessed by Multiple Gated Acquisition (MUGA) scan, or from echocardiogram to be performed within 28 days prior to start of treatment
Exclusion Criteria:
-
Received prior treatment with sunitinib or LY2510924
-
Received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
-
History of active cardiovascular disease within the previous 12 months, including any of the following:
-
Myocardial infarction
-
Unstable angina
-
Coronary artery/peripheral artery bypass graft
-
Congestive heart failure
-
Malignant hypertension
-
Cerebrovascular accident or transient ischemic attack
-
Symptomatic cardiac arrhythmias (Patients with chronic, stable, rate- controlled atrial fibrillation are eligible)
-
Exhibit uncontrolled hypertension ( [greater than] >150/100 [millimeters of mercury] mm/Hg despite optimal medical therapy), or history of poor compliance with antihypertensive treatment
-
Evidence of bleeding diathesis, National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage (less than) <4 weeks of starting the study treatment, coagulopathy, or thromboembolic event
-
Significant surgery (less than) <4 weeks of starting study treatment or a minor surgical procedure (less than) < 7 days prior to study treatment (Placement of a portacath or other venous access device does not require a waiting period)
-
Suffer from medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
-
Known or suspected allergy to any agent given in association with this trial
-
Prior palliative radiotherapy to metastatic lesion(s) is/are permitted, provided there is at least 1 measurable lesion that has not been irradiated. Radiotherapy must have been completed (greater than) >2 weeks prior to starting study treatment, and radiation-related side effects must have resolved
-
Pregnant or lactating women
-
Impairment of the gastrointestinal (GI) function or GI disease that may significantly alter the absorption of sunitinib
-
Current or recent (within 10 days of first dose of study treatment) daily use of aspirin ( [greater than] >325 [milligram] mg/day )
-
Serious nonhealing wounds, acute or nonhealing ulcers, or bone fractures
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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. | Scottsdale | Arizona | United States | 85258 |
| 2 | 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. | Norwich | Connecticut | United States | 06360 |
| 3 | 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. | Newark | Delaware | United States | 19713 |
| 4 | 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. | Fort Myers | Florida | United States | 33916 |
| 5 | 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. | Orlando | Florida | United States | 32804 |
| 6 | 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. | Pensacola | Florida | United States | 32503 |
| 7 | 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. | Gainesville | Georgia | United States | 30501 |
| 8 | 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. | Lawrenceville | Georgia | United States | 30045 |
| 9 | 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. | Bridgeton | Missouri | United States | 63044 |
| 10 | 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. | Springfield | Missouri | United States | 65804 |
| 11 | 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. | Omaha | Nebraska | United States | 68114 |
| 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. | Las Vegas | Nevada | United States | 89169 |
| 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. | Morristown | New Jersey | United States | 07960 |
| 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. | Cincinnati | Ohio | United States | 45242 |
| 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. | Lawton | Oklahoma | United States | 73506 |
| 16 | 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. | Columbia | South Carolina | United States | 29210 |
| 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. | Greenville | South Carolina | United States | 29605 |
| 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. | Chattanooga | Tennessee | United States | 37404 |
| 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. | Nashville | Tennessee | United States | 37203 |
| 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. | Fort Worth | Texas | United States | 76104 |
| 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. | Richmond | Virginia | United States | 23230 |
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)
None provided.More Information
Publications
None provided.- 14241
- I2V-MC-CXAB
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Participants who died (any cause) or had disease progression at the time the primary analysis were considered to be study completers. |
| Arm/Group Title | LY2510924 + Sunitinib | Sunitinib |
|---|---|---|
| Arm/Group Description | LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Period Title: Overall Study | ||
| STARTED | 73 | 37 |
| Received At Least One Dose of Study Drug | 72 | 36 |
| COMPLETED | 67 | 31 |
| NOT COMPLETED | 6 | 6 |
Baseline Characteristics
| Arm/Group Title | LY2510924 + Sunitinib | Sunitinib | Total |
|---|---|---|---|
| Arm/Group Description | LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | Total of all reporting groups |
| Overall Participants | 72 | 36 | 108 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.51
(11.332)
|
64.21
(9.474)
|
64.41
(10.705)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
24
33.3%
|
12
33.3%
|
36
33.3%
|
| Male |
48
66.7%
|
24
66.7%
|
72
66.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
2
5.6%
|
2
1.9%
|
| Not Hispanic or Latino |
71
98.6%
|
34
94.4%
|
105
97.2%
|
| Unknown or Not Reported |
1
1.4%
|
0
0%
|
1
0.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
4
5.6%
|
2
5.6%
|
6
5.6%
|
| White |
68
94.4%
|
34
94.4%
|
102
94.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
72
100%
|
36
100%
|
108
100%
|
Outcome Measures
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS is defined as the time from date of study Randomization to the first date of objectively determined progressive disease(PD) or death from any cause defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0).PD was defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study(including the baseline sum if that is the smallest).In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions was also considered PD.For participants still alive at the time of analysis and without evidence of tumor progression,PFS would be censored at the date of the most recent objective progression-free observation.For participants who receive subsequent anticancer therapy prior to objective disease progression or death,PFS was censored at the date of the last objective progression-free observation prior to the date of subsequent therapy. |
| Time Frame | Randomization to Measured Progressive Disease or Date of Death From Any Cause (Up to 67 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. Participants censored were LY2510924 + Sunitinib = 16 and Sunitinib=12. |
| Arm/Group Title | LY2510924 + Sunitinib | Sunitinib |
|---|---|---|
| Arm/Group Description | LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Measure Participants | 72 | 36 |
| Median (95% Confidence Interval) [Months] |
8.08
|
12.25
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2510924 + Sunitinib, Sunitinib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4318 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.2149 | |
| Confidence Interval |
(2-Sided) 95% 0.7462 to 1.9779 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR]) |
|---|---|
| Description | ORR is defined as the number of participants with a best response of CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression. |
| Time Frame | Baseline to Date of Tumor Response or Measured Progressive Disease or Date of Death from any Cause ((Up to 67 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | LY2510924 + Sunitinib | Sunitinib |
|---|---|---|
| Arm/Group Description | LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Measure Participants | 72 | 36 |
| Number (95% Confidence Interval) [percentage of participants] |
31.9
44.3%
|
38.9
108.1%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS is defined as the time from the date of study randomization to the date of death from any cause. For participants who were still alive as of the data cut-off date, OS time will be censored on the date of the participant's last contact (last contact for participants in post-discontinuation = last known alive date in mortality status). |
| Time Frame | Randomization to Date of Death from Any Cause (Up to 67 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. Participants censored were LY2510924 + Sunitinib=19 and Sunitinib=10. |
| Arm/Group Title | LY2510924 + Sunitinib | Sunitinib |
|---|---|---|
| Arm/Group Description | LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Measure Participants | 72 | 36 |
| Median (95% Confidence Interval) [months] |
24.18
|
23.82
|
| Title | Duration of Overall Response (DOR) |
|---|---|
| Description | DOR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. |
| Time Frame | Date of First Response to Date of Progressive Disease (Up to 67 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. Participants censored were LY2510924 + Sunitinib=7 and Sunitinib=7. |
| Arm/Group Title | LY2510924 + Sunitinib | Sunitinib |
|---|---|---|
| Arm/Group Description | LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Measure Participants | 72 | 36 |
| Median (95% Confidence Interval) [Months] |
11.30
|
12.42
|
| Title | Duration of Complete Response |
|---|---|
| Description | Duration of complete response is defined as the time from the date when the measurement criteria are met for complete response until the date of first observation of objective disease progression (taking as reference for PD the smallest measurements recorded since the treatment started). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. |
| Time Frame | Date of Complete Response to the Date of Progressive Disease (Up to 67 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug who had CR. |
| Arm/Group Title | LY2510924 + Sunitinib | Sunitinib |
|---|---|---|
| Arm/Group Description | LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Measure Participants | 0 | 1 |
| Median (95% Confidence Interval) [months] |
10
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least one dose of study drug. | |||
| Arm/Group Title | LY2510924 + Sunitinib | Sunitinib | ||
| Arm/Group Description | LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | ||
All Cause Mortality |
||||
| LY2510924 + Sunitinib | Sunitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| LY2510924 + Sunitinib | Sunitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 31/72 (43.1%) | 10/36 (27.8%) | ||
| Blood and lymphatic system disorders | ||||
| Coagulopathy | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Febrile neutropenia | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Idiopathic thrombocytopenic purpura | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Cardiac disorders | ||||
| Cardiac arrest | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Cardiac failure congestive | 2/72 (2.8%) | 2 | 0/36 (0%) | 0 |
| Myocardial infarction | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Pericardial effusion | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Diarrhoea | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Gastrointestinal haemorrhage | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Small intestinal obstruction | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| General disorders | ||||
| Asthenia | 2/72 (2.8%) | 2 | 0/36 (0%) | 0 |
| Disease progression | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Fatigue | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Pain | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Pyrexia | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Bile duct stone | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Infections and infestations | ||||
| Bacteraemia | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Cellulitis | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Clostridial infection | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Pancreas infection | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Peridiverticular abscess | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Pneumonia | 1/72 (1.4%) | 1 | 1/36 (2.8%) | 1 |
| Post procedural infection | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Urinary tract infection | 1/72 (1.4%) | 2 | 0/36 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 2/72 (2.8%) | 3 | 2/36 (5.6%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Haemarthrosis | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Intracranial tumour haemorrhage | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Metastatic renal cell carcinoma | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Squamous cell carcinoma | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Nervous system disorders | ||||
| Brain oedema | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Central nervous system lesion | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Convulsion | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Dizziness | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Syncope | 2/72 (2.8%) | 2 | 1/36 (2.8%) | 2 |
| Psychiatric disorders | ||||
| Delirium | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Mental status changes | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Renal and urinary disorders | ||||
| Cystitis haemorrhagic | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Haematuria | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Renal failure | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Renal failure acute | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 3/72 (4.2%) | 3 | 0/36 (0%) | 0 |
| Haemoptysis | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Pleural effusion | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Pulmonary embolism | 1/72 (1.4%) | 1 | 1/36 (2.8%) | 1 |
| Pulmonary oedema | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Respiratory arrest | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash maculo-papular | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Surgical and medical procedures | ||||
| Spinal operation | 0/72 (0%) | 0 | 1/36 (2.8%) | 1 |
| Vascular disorders | ||||
| Deep vein thrombosis | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
| Embolism | 1/72 (1.4%) | 1 | 0/36 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| LY2510924 + Sunitinib | Sunitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 70/72 (97.2%) | 35/36 (97.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 26/72 (36.1%) | 95 | 7/36 (19.4%) | 10 |
| Leukocytosis | 5/72 (6.9%) | 6 | 1/36 (2.8%) | 1 |
| Leukopenia | 3/72 (4.2%) | 4 | 5/36 (13.9%) | 8 |
| Neutropenia | 6/72 (8.3%) | 22 | 4/36 (11.1%) | 18 |
| Thrombocytopenia | 20/72 (27.8%) | 57 | 9/36 (25%) | 12 |
| Endocrine disorders | ||||
| Hypothyroidism | 11/72 (15.3%) | 11 | 3/36 (8.3%) | 3 |
| Eye disorders | ||||
| Vision blurred | 5/72 (6.9%) | 5 | 0/36 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 6/72 (8.3%) | 9 | 1/36 (2.8%) | 2 |
| Abdominal pain upper | 5/72 (6.9%) | 5 | 1/36 (2.8%) | 1 |
| Constipation | 16/72 (22.2%) | 19 | 6/36 (16.7%) | 10 |
| Diarrhoea | 28/72 (38.9%) | 55 | 18/36 (50%) | 39 |
| Dry mouth | 6/72 (8.3%) | 7 | 3/36 (8.3%) | 3 |
| Dyspepsia | 8/72 (11.1%) | 8 | 4/36 (11.1%) | 6 |
| Dysphagia | 2/72 (2.8%) | 2 | 2/36 (5.6%) | 3 |
| Flatulence | 4/72 (5.6%) | 5 | 0/36 (0%) | 0 |
| Gastrooesophageal reflux disease | 6/72 (8.3%) | 8 | 2/36 (5.6%) | 4 |
| Glossodynia | 2/72 (2.8%) | 2 | 2/36 (5.6%) | 2 |
| Haemorrhoids | 5/72 (6.9%) | 9 | 1/36 (2.8%) | 1 |
| Nausea | 35/72 (48.6%) | 50 | 18/36 (50%) | 33 |
| Oral pain | 6/72 (8.3%) | 6 | 4/36 (11.1%) | 4 |
| Stomatitis | 15/72 (20.8%) | 19 | 7/36 (19.4%) | 11 |
| Vomiting | 18/72 (25%) | 32 | 8/36 (22.2%) | 14 |
| General disorders | ||||
| Asthenia | 9/72 (12.5%) | 10 | 0/36 (0%) | 0 |
| Chest pain | 5/72 (6.9%) | 5 | 1/36 (2.8%) | 1 |
| Chills | 6/72 (8.3%) | 7 | 0/36 (0%) | 0 |
| Fatigue | 50/72 (69.4%) | 96 | 20/36 (55.6%) | 37 |
| Injection site pruritus | 6/72 (8.3%) | 6 | 0/36 (0%) | 0 |
| Injection site reaction | 6/72 (8.3%) | 6 | 0/36 (0%) | 0 |
| Mucosal inflammation | 17/72 (23.6%) | 25 | 10/36 (27.8%) | 15 |
| Oedema | 3/72 (4.2%) | 3 | 2/36 (5.6%) | 2 |
| Oedema peripheral | 17/72 (23.6%) | 27 | 6/36 (16.7%) | 8 |
| Pain | 3/72 (4.2%) | 3 | 2/36 (5.6%) | 13 |
| Pyrexia | 10/72 (13.9%) | 10 | 2/36 (5.6%) | 2 |
| Infections and infestations | ||||
| Herpes zoster | 0/72 (0%) | 0 | 2/36 (5.6%) | 2 |
| Oral candidiasis | 0/72 (0%) | 0 | 2/36 (5.6%) | 2 |
| Sinusitis | 9/72 (12.5%) | 11 | 2/36 (5.6%) | 2 |
| Upper respiratory tract infection | 6/72 (8.3%) | 6 | 2/36 (5.6%) | 2 |
| Urinary tract infection | 8/72 (11.1%) | 16 | 1/36 (2.8%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Contusion | 6/72 (8.3%) | 7 | 2/36 (5.6%) | 3 |
| Excoriation | 1/72 (1.4%) | 1 | 2/36 (5.6%) | 2 |
| Fall | 4/72 (5.6%) | 4 | 0/36 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 5/72 (6.9%) | 5 | 0/36 (0%) | 0 |
| Aspartate aminotransferase increased | 7/72 (9.7%) | 8 | 0/36 (0%) | 0 |
| Blood alkaline phosphatase increased | 5/72 (6.9%) | 5 | 2/36 (5.6%) | 2 |
| Blood creatinine increased | 5/72 (6.9%) | 6 | 5/36 (13.9%) | 7 |
| Weight decreased | 12/72 (16.7%) | 15 | 9/36 (25%) | 13 |
| Weight increased | 2/72 (2.8%) | 4 | 2/36 (5.6%) | 3 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 17/72 (23.6%) | 26 | 8/36 (22.2%) | 14 |
| Dehydration | 12/72 (16.7%) | 19 | 5/36 (13.9%) | 12 |
| Hypercalcaemia | 3/72 (4.2%) | 4 | 3/36 (8.3%) | 4 |
| Hypoalbuminaemia | 2/72 (2.8%) | 2 | 3/36 (8.3%) | 3 |
| Hypocalcaemia | 2/72 (2.8%) | 2 | 3/36 (8.3%) | 6 |
| Hypokalaemia | 3/72 (4.2%) | 3 | 2/36 (5.6%) | 2 |
| Hyponatraemia | 5/72 (6.9%) | 8 | 1/36 (2.8%) | 1 |
| Vitamin b12 deficiency | 1/72 (1.4%) | 1 | 2/36 (5.6%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 9/72 (12.5%) | 23 | 2/36 (5.6%) | 9 |
| Back pain | 8/72 (11.1%) | 9 | 2/36 (5.6%) | 3 |
| Bone pain | 4/72 (5.6%) | 6 | 0/36 (0%) | 0 |
| Muscle spasms | 4/72 (5.6%) | 4 | 1/36 (2.8%) | 1 |
| Muscular weakness | 6/72 (8.3%) | 8 | 3/36 (8.3%) | 4 |
| Musculoskeletal pain | 5/72 (6.9%) | 5 | 1/36 (2.8%) | 2 |
| Myalgia | 7/72 (9.7%) | 8 | 2/36 (5.6%) | 2 |
| Pain in extremity | 7/72 (9.7%) | 9 | 4/36 (11.1%) | 4 |
| Pain in jaw | 0/72 (0%) | 0 | 2/36 (5.6%) | 3 |
| Nervous system disorders | ||||
| Dizziness | 17/72 (23.6%) | 20 | 7/36 (19.4%) | 11 |
| Dysgeusia | 23/72 (31.9%) | 27 | 11/36 (30.6%) | 14 |
| Headache | 10/72 (13.9%) | 14 | 6/36 (16.7%) | 6 |
| Psychiatric disorders | ||||
| Anxiety | 9/72 (12.5%) | 11 | 3/36 (8.3%) | 4 |
| Confusional state | 4/72 (5.6%) | 6 | 1/36 (2.8%) | 3 |
| Depression | 7/72 (9.7%) | 7 | 2/36 (5.6%) | 2 |
| Insomnia | 7/72 (9.7%) | 9 | 5/36 (13.9%) | 7 |
| Renal and urinary disorders | ||||
| Dysuria | 4/72 (5.6%) | 4 | 1/36 (2.8%) | 1 |
| Haematuria | 8/72 (11.1%) | 9 | 1/36 (2.8%) | 1 |
| Reproductive system and breast disorders | ||||
| Vaginal discharge | 0/24 (0%) | 0 | 1/12 (8.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 14/72 (19.4%) | 19 | 7/36 (19.4%) | 10 |
| Dyspnoea | 13/72 (18.1%) | 16 | 2/36 (5.6%) | 2 |
| Epistaxis | 13/72 (18.1%) | 16 | 0/36 (0%) | 0 |
| Pleuritic pain | 1/72 (1.4%) | 2 | 2/36 (5.6%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 4/72 (5.6%) | 4 | 0/36 (0%) | 0 |
| Dermatitis | 0/72 (0%) | 0 | 2/36 (5.6%) | 4 |
| Dermatitis acneiform | 5/72 (6.9%) | 6 | 1/36 (2.8%) | 1 |
| Dry skin | 9/72 (12.5%) | 9 | 3/36 (8.3%) | 4 |
| Palmar-plantar erythrodysaesthesia syndrome | 12/72 (16.7%) | 38 | 6/36 (16.7%) | 6 |
| Pruritus | 5/72 (6.9%) | 5 | 2/36 (5.6%) | 5 |
| Rash | 19/72 (26.4%) | 28 | 4/36 (11.1%) | 6 |
| Skin lesion | 5/72 (6.9%) | 7 | 1/36 (2.8%) | 1 |
| Vascular disorders | ||||
| Hypertension | 17/72 (23.6%) | 26 | 12/36 (33.3%) | 18 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
| ClinicalTrials.gov@lilly.com |
- 14241
- I2V-MC-CXAB