A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma
Sponsor
Sumitomo Pharma Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT02347917
Collaborator
(none)
28
2
1
39.9
14
0.4
Study Details
Study Description
Brief Summary
This is an open-label, multicenter, phase 1/2 study of BBI608 in combination with pemetrexed and cisplatin chemotherapy as a 1st line treatment for Malignant Pleural Mesothelioma (MPM).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
28 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Clinical Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma
Actual Study Start Date
:
Feb 1, 2015
Actual Primary Completion Date
:
May 31, 2018
Actual Study Completion Date
:
May 31, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BBI608 puls pemetrexed and cisplatin
|
Drug: BBI608
480 mg orally twice daily (960 mg total daily dose)
Drug: Pemetrexed
500 mg/m2 I.V. infusion on Day 1 of each treatment cycle (except for cycle 1, in which Pemetrexed will be given on Day 3).
Drug: Cisplatin
75 mg/m2 I.V. infusion on Day 1 of each treatment cycle (except for Cycle 1, in which Cisplatin will be given on Day 3).
|
Outcome Measures
Primary Outcome Measures
- Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) [Between initial dosing of the investigational drug and final evaluation in the follow-up observation period, about 17 months]
An AE is any untoward medical occurrence in a study subject administered an investigational drug and which does not necessarily have a causal relationship with this treatment. A SAE was an AE that met one or more of the following criteria: Results in death Is life-threatening Requires hospitalization or prolongation of existing hospitalization Results in persistent or significant disability or incapacity Is a congenital anomaly or birth defect Is an important medical event that may jeopardize the subject or may require a medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization. An ADR was defined as adverse events assessed to be related to the investigational drug
- Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs) [From Day 1 of Cycle 1 to Day 24 pre-dose examination (23 days)]
DLT was defined as an adverse event meeting any of the following that occurred during the DLT evaluation period in any participants given BBI608 with the causal relationship to BBI608 assessed as "Definite," "Probable," or "Possible." The severity of adverse events was graded according to the CTCAE v4.0-JCOG. Grade 4 neutropenia persisting for ≥ 7 days Grade ≥ 3 febrile neutropenia persisting for ≥ 5 days Grade 3 thrombocytopenia requiring platelet transfusions, grade 4 thrombocytopenia Grade ≥ 3 non-hematotoxicity except the following: Inappetence, nausea, vomiting and electrolyte abnormality which, within 3 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment Diarrhoea and fatigue which, within 5 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment Other clinically significant signs in the opinion of the investigator
- Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP [Cycle 1 Day 1 (Cmax only) and Day 23]
- Phase 1 Part: Area Under the Concentration-time Curve [Cycle 1 Day 1 and Day 23]
AUC0-12: Area under the concentration-time curve from time zero to 12 hours, AUC0-24: Area under the concentration-time curve from time zero to 24 hours, AUC0-inf: Area under the concentration-time curve from time zero to infinity
- Phase 2 Part: Progression-free Survival (PFS) [From BBI608 administration to documented PD or death, whichever is earlier, about 17 months]
PFS was defined as the time from BBI608 administration to documented PD (as assessed according to the mRECIST or RECIST 1.1) or death, whichever is earlier. The result of imaging assessment by the imaging assessment committee was used for phase 2 part.
Secondary Outcome Measures
- Best Overall Response [Every 6 weeks from the first dose of BBI608 until Week 30, and every 9 weeks from Week 31.]
The best overall response is the best response recorded from the start of the study treatment until the end of treatment. The RECIST 1.1 was used for the evaluation of tumor response and overall response in patients with NSCLC, and also the evaluation of any non-pleural lesions in patients with MPM. The mRECIST was used for the evaluation of tumor response and overall response in patients with MPM. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part.
- Response Rate (RR) and Disease Control Rate (DCR) [From BBI608 administration to death from any cause, about 17 months]
Response rate (RR): Proportion of subjects whose best overall response is CR or PR. Disease control rate (DCR): Proportion of subjects whose best overall response is CR, PR or SD. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part.
- Overall Survival(OS) [From BBI608 administration to death from any cause, up to 31 months]
OS was defined as the time from BBI608 administration to death from any cause. Participants alive at final observation or lost to follow-up were censored at their last contact (i.e., visit or telephone) date.
- Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) [Every 6 weeks from the first dose of BBI608 until Week 30, and then every 9 weeks from Week 31 [Actually up to Week 111]]
- Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) [Every 6 weeks from the first dose of BBI608 until Week 30, and then every 9 weeks from Week 31 [Actually up to Week 111]]
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Phase 1
Inclusion Criteria:
-
Histologically confirmed diagnosis of Malignant Pleural Mesothelioma (MPM) or Non-Small Cell Lung Cancer (NSCLC).
-
Measurable disease as defined by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) for MPM or the RECIST 1.1 for NSCLC.
-
≥ 20 years of age.
-
Provision of written informed consent.
-
For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose.
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
-
Hemoglobin (Hb) ≥ 9.0 g/dL.
-
Neutrophils ≥ 1500/μL.
-
Platelets ≥ 100,000/μL.
-
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5-fold the upper limit of normal range (ULN) [≤ 5-fold ULN with any liver metastasis].
-
Total bilirubin ≤ 1.5-fold ULN.
-
Creatinine clearance (estimated value) ≥ 60 mL/min.
-
Life expectancy ≥ 3 months.
-
Females of childbearing potential have a negative urine pregnancy test.
Phase 2
Inclusion Criteria:
-
Histologically confirmed diagnosis of MPM.
-
Treatment naïve and not indicated for resection.
-
Measurable disease as defined by the modified RECIST.
-
≥ 20 years of age.
-
Provision of written informed consent.
-
For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose.
-
ECOG Performance Status of 0 or 1.
-
Hb ≥ 9.0 g/dL.
-
Neutrophils ≥ 1500/μL.
-
Platelets ≥ 100,000/μL.
-
AST and ALT ≤ 2.5-fold ULN [≤ 5-fold ULN for patients with any liver metastasis].
-
Total bilirubin ≤ 1.5-fold ULN.
-
Creatinine clearance (estimated value) > 60 mL/min.
-
Life expectancy ≥ 3 months.
-
Females of childbearing potential have a negative urine pregnancy test.
Both Phase 1 and 2
Exclusion Criteria:
-
Prior anti-cancer chemotherapy and radiotherapy.
-
Prior hormonal therapy, immunotherapy, thermotherapy, operation.
-
Any brain metastasis requiring treatment or symptomatic.
-
Active multiple primary cancers.
-
Crohn's disease, ulcerative colitis, small intestine resection.
-
Abnormal ECGs.
-
Prior myocardial infarction.
-
Current use of antiarrhythmic medication.
-
Uncontrolled concurrent diseases.
-
Known severe hypersensitivity to pemetrexed, cisplatin or other drugs containing platinum.
-
Women who are pregnant or breastfeeding.
-
Received other investigational drugs.
-
Unable or unwilling to swallow BBI608 capsules daily.
-
Prior treatment with BBI608.
-
Ineligible for participation in the study in the opinion of the Investigators.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Cancer Center Hospital East | Chiba | Japan | ||
| 2 | National Cancer Center Hospital | Tokyo | Japan |
Sponsors and Collaborators
- Sumitomo Pharma Co., Ltd.
Investigators
- Study Director: Sumitomo Pharma Co., Ltd. Japan, Sumitomo Pharma Co., Ltd.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Sumitomo Pharma Co., Ltd.
ClinicalTrials.gov Identifier:
NCT02347917
Other Study ID Numbers:
- D8807005
First Posted:
Jan 28, 2015
Last Update Posted:
Apr 12, 2022
Last Verified:
Apr 1, 2022
Study Results
Participant Flow
| Recruitment Details | The study conducted from February 2015 to December 2017 and a total of 28 participants were enrolled at 9 medical institutions in Japan. |
|---|---|
| Pre-assignment Detail | This clinical study consisted of two parts: Phase 1 and Phase 2. The study proceeded to Phase 2 part after Phase 1 part demonstrated the tolerability of BBI608 combined with Pem plus CDDP based on complete assessment of DLT. Participants were NOT enrolled in Phase 1 and Phase 2 in duplicate. |
| Arm/Group Title | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) |
|---|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Period Title: Overall Study | ||
| STARTED | 4 | 24 |
| Discontinued beforeBBI608 Administration | 0 | 0 |
| Start BBI608 Administration | 4 | 24 |
| Discontinued in DLT Evaluation Period | 1 | 0 |
| Complete DLT Evaluation Period | 3 | 0 |
| Discontinued After BBI608 Administration | 4 | 24 |
| Discontinued Before Survival Observation | 0 | 1 |
| COMPLETED | 4 | 23 |
| NOT COMPLETED | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Total |
|---|---|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Total of all reporting groups |
| Overall Participants | 4 | 24 | 28 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.5
(5.00)
|
65.6
(10.71)
|
65.5
(9.854)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1
25%
|
2
8.3%
|
3
10.7%
|
| Male |
3
75%
|
22
91.7%
|
25
89.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
4
100%
|
24
100%
|
28
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
4
100%
|
24
100%
|
28
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Primary cancer (Count of Participants) | |||
| MPM |
1
25%
|
24
100%
|
25
89.3%
|
| NSCLC |
3
75%
|
0
0%
|
3
10.7%
|
| Weight (kg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg] |
58.53
(10.278)
|
63.11
(7.661)
|
62.45
(8.025)
|
| ECOG PS (Count of Participants) | |||
| 0 |
3
75%
|
11
45.8%
|
14
50%
|
| 1 |
1
25%
|
13
54.2%
|
14
50%
|
| 2<= |
0
0%
|
0
0%
|
0
0%
|
| Disease classification (Count of Participants) | |||
| STAGE I |
0
0%
|
0
0%
|
0
0%
|
| STAGE II |
0
0%
|
2
8.3%
|
2
7.1%
|
| STAGE III |
0
0%
|
5
20.8%
|
5
17.9%
|
| STAGE IV |
1
25%
|
17
70.8%
|
18
64.3%
|
| STAGE I |
0
0%
|
0
0%
|
0
0%
|
| STAGE II |
0
0%
|
0
0%
|
0
0%
|
| STAGE III |
0
0%
|
0
0%
|
0
0%
|
| STAGE IV |
3
75%
|
0
0%
|
3
10.7%
|
| Tissue classification (MPM) (Count of Participants) | |||
| EPITHELIOID |
1
25%
|
16
66.7%
|
17
60.7%
|
| SARCOMATOID |
0
0%
|
3
12.5%
|
3
10.7%
|
| BIPHASIC |
0
0%
|
5
20.8%
|
5
17.9%
|
| OTHER |
0
0%
|
0
0%
|
0
0%
|
| Tissue classification (NSCLC) (Count of Participants) | |||
| ADENOCARCINOMA |
3
75%
|
0
0%
|
3
10.7%
|
| SQUAMOUS CELL CARCINOMA |
0
0%
|
0
0%
|
0
0%
|
| LARGE CELL CARCINOMA |
0
0%
|
0
0%
|
0
0%
|
| OTHER |
0
0%
|
0
0%
|
0
0%
|
| Metastases (Count of Participants) | |||
| Yes |
3
75%
|
11
45.8%
|
14
50%
|
| No |
1
25%
|
13
54.2%
|
14
50%
|
| Disease duration (month) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [month] |
3.91
(2.866)
|
0.91
(0.726)
|
1.34
(1.562)
|
Outcome Measures
| Title | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) |
|---|---|
| Description | An AE is any untoward medical occurrence in a study subject administered an investigational drug and which does not necessarily have a causal relationship with this treatment. A SAE was an AE that met one or more of the following criteria: Results in death Is life-threatening Requires hospitalization or prolongation of existing hospitalization Results in persistent or significant disability or incapacity Is a congenital anomaly or birth defect Is an important medical event that may jeopardize the subject or may require a medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization. An ADR was defined as adverse events assessed to be related to the investigational drug |
| Time Frame | Between initial dosing of the investigational drug and final evaluation in the follow-up observation period, about 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis populations (Phase 1 part) |
| Arm/Group Title | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) |
|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 4 |
| Any AEs |
4
100%
|
| AEs leading to death |
0
0%
|
| Serious AEs |
0
0%
|
| AEs leading to drug withdrawn (BBI608) |
1
25%
|
| AEs leading to drug interrupted (BBI608) |
1
25%
|
| AEs leading to dose reduced (BBI608) |
0
0%
|
| Any ADRs |
4
100%
|
| ADRs leading to death |
0
0%
|
| Serious ADRs |
0
0%
|
| ADRs leading to drug withdrawn (BBI608) |
1
25%
|
| ADRs leading to drug interrupted (BBI608) |
1
25%
|
| ADRs leading to dose reduced (BBI608) |
0
0%
|
| Title | Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs) |
|---|---|
| Description | DLT was defined as an adverse event meeting any of the following that occurred during the DLT evaluation period in any participants given BBI608 with the causal relationship to BBI608 assessed as "Definite," "Probable," or "Possible." The severity of adverse events was graded according to the CTCAE v4.0-JCOG. Grade 4 neutropenia persisting for ≥ 7 days Grade ≥ 3 febrile neutropenia persisting for ≥ 5 days Grade 3 thrombocytopenia requiring platelet transfusions, grade 4 thrombocytopenia Grade ≥ 3 non-hematotoxicity except the following: Inappetence, nausea, vomiting and electrolyte abnormality which, within 3 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment Diarrhoea and fatigue which, within 5 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment Other clinically significant signs in the opinion of the investigator |
| Time Frame | From Day 1 of Cycle 1 to Day 24 pre-dose examination (23 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT evaluable population (3 participants with NSCLC in Phase 1 part) 1 participant with MPM was excluded from DLT evaluable population because the BBI608 treatment compliance rate during DLT evaluation period did not meet the rate of 80% which of assessable for DLT and no adverse events assessed as DLT occurred. |
| Arm/Group Title | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) |
|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 3 |
| Count of Participants [Participants] |
0
0%
|
| Title | Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 (Cmax only) and Day 23 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) analysis population 1 participant with MPM of 4 participants in the pharmacokinetic analysis population completed BBI608 administration on Day 14 in Cycle 1 and therefore was not included in the analysis for Cmax and AUC on Day 23. |
| Arm/Group Title | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) |
|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 4 |
| Day 1: Cmax |
307.5
|
| Day 23: Cmax |
473.7
|
| Day 23: Cmin |
196.1
|
| Title | Phase 1 Part: Area Under the Concentration-time Curve |
|---|---|
| Description | AUC0-12: Area under the concentration-time curve from time zero to 12 hours, AUC0-24: Area under the concentration-time curve from time zero to 24 hours, AUC0-inf: Area under the concentration-time curve from time zero to infinity |
| Time Frame | Cycle 1 Day 1 and Day 23 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) analysis population 1 participant with MPM of 4 participants in the pharmacokinetic analysis population completed BBI608 administration on Day 14 in Cycle 1 and therefore was not included in the analysis for Cmax and AUC on Day 23. |
| Arm/Group Title | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) |
|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 4 |
| Day 1: AUC0-12 |
1814.3
|
| Day 1: AUC0-24 |
2223.8
|
| Day 1: AUC0-inf |
2413.5
|
| Day 23: AUC0-12 |
3797.0
|
| Day 23: AUC0-24 |
6103.7
|
| Day 23: AUC0-inf |
10762.7
|
| Title | Phase 2 Part: Progression-free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from BBI608 administration to documented PD (as assessed according to the mRECIST or RECIST 1.1) or death, whichever is earlier. The result of imaging assessment by the imaging assessment committee was used for phase 2 part. |
| Time Frame | From BBI608 administration to documented PD or death, whichever is earlier, about 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). |
| Arm/Group Title | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) |
|---|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608(480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 24 | 25 |
| Median (95% Confidence Interval) [month] |
5.59
|
5.59
|
| Title | Best Overall Response |
|---|---|
| Description | The best overall response is the best response recorded from the start of the study treatment until the end of treatment. The RECIST 1.1 was used for the evaluation of tumor response and overall response in patients with NSCLC, and also the evaluation of any non-pleural lesions in patients with MPM. The mRECIST was used for the evaluation of tumor response and overall response in patients with MPM. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part. |
| Time Frame | Every 6 weeks from the first dose of BBI608 until Week 30, and every 9 weeks from Week 31. |
Outcome Measure Data
| Analysis Population Description |
|---|
| modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). |
| Arm/Group Title | NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem +CDDP (Phase 1 Part) | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 3 | 1 | 4 | 24 | 25 |
| Complete response (CR) |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
| Partial response (PR) |
0
0%
|
0
0%
|
0
0%
|
8
NaN
|
8
NaN
|
| Stable disease (SD) |
3
75%
|
0
0%
|
3
10.7%
|
11
NaN
|
11
NaN
|
| Progressive disease (PD) |
0
0%
|
0
0%
|
0
0%
|
2
NaN
|
2
NaN
|
| Not evaluated (NE) |
0
0%
|
1
4.2%
|
1
3.6%
|
3
NaN
|
4
NaN
|
| Title | Response Rate (RR) and Disease Control Rate (DCR) |
|---|---|
| Description | Response rate (RR): Proportion of subjects whose best overall response is CR or PR. Disease control rate (DCR): Proportion of subjects whose best overall response is CR, PR or SD. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part. |
| Time Frame | From BBI608 administration to death from any cause, about 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). |
| Arm/Group Title | NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem +CDDP (Phase 1 Part) | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 3 | 1 | 4 | 24 | 25 |
| Response rate (RR) |
0
0%
|
0
0%
|
0
0%
|
8
NaN
|
8
NaN
|
| Disease control rate (DCR) |
3
75%
|
0
0%
|
3
10.7%
|
19
NaN
|
19
NaN
|
| Title | Overall Survival(OS) |
|---|---|
| Description | OS was defined as the time from BBI608 administration to death from any cause. Participants alive at final observation or lost to follow-up were censored at their last contact (i.e., visit or telephone) date. |
| Time Frame | From BBI608 administration to death from any cause, up to 31 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). |
| Arm/Group Title | NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem +CDDP (Phase 1 Part) | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 3 | 1 | 4 | 24 | 25 |
| Median (Full Range) [month] |
19.81
|
30.1
|
NA
|
12.14
|
12.75
|
| Title | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) |
|---|---|
| Description | |
| Time Frame | Every 6 weeks from the first dose of BBI608 until Week 30, and then every 9 weeks from Week 31 [Actually up to Week 111] |
Outcome Measure Data
| Analysis Population Description |
|---|
| modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). In respiratory function tests, data from 1 participant with MPM in Phase 1 part were not collected. |
| Arm/Group Title | NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem +CDDP (Phase 1 Part) | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 3 | 0 | 4 | 24 | 25 |
| The change from baseline in VC: 6 weeks |
70.0
|
70.0
|
30.0
|
30.0
|
|
| The change from baseline in VC: 12 weeks |
110.0
|
110.0
|
0.0
|
0.0
|
|
| The change from baseline in VC: 18 weeks |
-60.0
|
-60.0
|
-70.0
|
-70.0
|
|
| The change from baseline in VC: 24 weeks |
-290.0
|
-290.0
|
-50.0
|
-50.0
|
|
| The change from baseline in VC: 30 weeks |
-240.0
|
-240.0
|
20.0
|
20.0
|
|
| The change from baseline in VC: 39 weeks |
-305.0
|
-305.0
|
30.0
|
30.0
|
|
| The change from baseline in VC: 48 weeks |
NA
|
NA
|
15.0
|
15.0
|
|
| The change from baseline in VC: 57 weeks |
NA
|
NA
|
-20.0
|
-20.0
|
|
| The change from baseline in VC: 66 weeks |
NA
|
NA
|
300.0
|
300.0
|
|
| The change from baseline in VC: 75 weeks |
175.0
|
175.0
|
|||
| The change from baseline in VC: 84 weeks |
145.0
|
145.0
|
|||
| The change from baseline in VC: 93 weeks |
-205.0
|
-205.0
|
|||
| The change from baseline in VC: 102 weeks |
NA
|
NA
|
|||
| The change from baseline in VC: 111 weeks |
NA
|
NA
|
|||
| The change from baseline in FVC: 6 weeks |
0.0
|
0.0
|
35.0
|
35.0
|
|
| The change from baseline in FVC: 12 weeks |
80.0
|
80.0
|
10.0
|
10.0
|
|
| The change from baseline in FVC: 18 weeks |
-20.0
|
-20.0
|
-140.0
|
-140.0
|
|
| The change from baseline in FVC: 24 weeks |
-155.0
|
-155.0
|
-50.0
|
-50.0
|
|
| The change from baseline in FVC: 30 weeks |
-265.0
|
-265.0
|
150.0
|
150.0
|
|
| The change from baseline in FVC: 39 weeks |
-345.0
|
-345.0
|
-35.0
|
-35.0
|
|
| The change from baseline in FVC: 48 weeks |
NA
|
NA
|
70.0
|
70.0
|
|
| The change from baseline in FVC: 57 weeks |
NA
|
NA
|
60.0
|
60.0
|
|
| The change from baseline in FVC: 66 weeks |
NA
|
NA
|
300.0
|
300.0
|
|
| The change from baseline in FVC: 75 weeks |
50.0
|
50.0
|
|||
| The change from baseline in FVC: 84 weeks |
10.0
|
10.0
|
|||
| The change from baseline in FVC: 93 weeks |
-230.0
|
-230.0
|
|||
| The change from baseline in FVC: 102 weeks |
NA
|
NA
|
|||
| The change from baseline in FVC: 111 weeks |
NA
|
NA
|
| Title | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) |
|---|---|
| Description | |
| Time Frame | Every 6 weeks from the first dose of BBI608 until Week 30, and then every 9 weeks from Week 31 [Actually up to Week 111] |
Outcome Measure Data
| Analysis Population Description |
|---|
| modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). In respiratory function tests, data from 1 participant with MPM in Phase 1 part were not collected. |
| Arm/Group Title | NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem +CDDP (Phase 1 Part) | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) |
|---|---|---|---|---|---|
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. |
| Measure Participants | 3 | 0 | 4 | 24 | 25 |
| The change from baseline in FEV1: 6 weeks |
0.160
|
0.160
|
0.050
|
0.050
|
|
| The change from baseline in FEV1: 12 weeks |
0.070
|
0.070
|
-0.130
|
-0.130
|
|
| The change from baseline in FEV1: 18 weeks |
0.000
|
0.000
|
-0.110
|
-0.110
|
|
| The change from baseline in FEV1: 24 weeks |
-0.010
|
-0.010
|
-0.040
|
-0.040
|
|
| The change from baseline in FEV1: 30 weeks |
-0.055
|
-0.055
|
-0.030
|
-0.030
|
|
| The change from baseline in FEV1: 39 weeks |
-0.140
|
-0.140
|
-0.050
|
-0.050
|
|
| The change from baseline in FEV1: 48 weeks |
NA
|
NA
|
0.115
|
0.115
|
|
| The change from baseline in FEV1: 57 weeks |
NA
|
NA
|
0.010
|
0.010
|
|
| The change from baseline in FEV1: 66 weeks |
NA
|
NA
|
0.085
|
0.085
|
|
| The change from baseline in FEV1: 75 weeks |
-0.045
|
-0.045
|
|||
| The change from baseline in FEV1: 84 weeks |
-0.130
|
-0.130
|
|||
| The change from baseline in FEV1: 93 weeks |
-0.215
|
-0.215
|
|||
| The change from baseline in FEV1: 102 weeks |
NA
|
NA
|
|||
| The change from baseline in FEV1: 111 weeks |
NA
|
NA
|
Adverse Events
| Time Frame | During a period from initial dosing of investigational drug to final evaluation in the follow-up observation period. up to 31 months for deaths, up to 11 months for Serious and Other (Not Including Serious) Adverse Events | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety analysis population [separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25)] | |||||
| Arm/Group Title | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | |||
| Arm/Group Description | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles. Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | |||
All Cause Mortality |
||||||
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 19/24 (79.2%) | 21/25 (84%) | |||
Serious Adverse Events |
||||||
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 7/24 (29.2%) | 7/25 (28%) | |||
| Gastrointestinal disorders | ||||||
| Colitis | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Enterocolitis | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Gastric ulcer | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Infections and infestations | ||||||
| Bronchopneumonia | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Sepsis | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Investigations | ||||||
| Platelet count decreased | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Neuroendocrine carcinoma | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Psychiatric disorders | ||||||
| Delirium | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Vascular disorders | ||||||
| Thrombosis | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 24/24 (100%) | 25/25 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 4/4 (100%) | 4 | 14/24 (58.3%) | 15 | 15/25 (60%) | 16 |
| Ear and labyrinth disorders | ||||||
| Hearing impaired | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Tinnitus | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Vertigo positional | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Abdominal distension | 1/4 (25%) | 1 | 0/24 (0%) | 0 | 0/25 (0%) | 0 |
| Abdominal pain | 1/4 (25%) | 1 | 2/24 (8.3%) | 3 | 2/25 (8%) | 3 |
| Abdominal pain upper | 0/4 (0%) | 0 | 3/24 (12.5%) | 3 | 3/25 (12%) | 3 |
| Constipation | 1/4 (25%) | 1 | 14/24 (58.3%) | 22 | 14/25 (56%) | 22 |
| Diarrhoea | 4/4 (100%) | 8 | 24/24 (100%) | 54 | 25/25 (100%) | 55 |
| Faecal incontinence | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Gastritis | 1/4 (25%) | 1 | 5/24 (20.8%) | 5 | 5/25 (20%) | 5 |
| Haemorrhoids | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Nausea | 3/4 (75%) | 5 | 21/24 (87.5%) | 49 | 22/25 (88%) | 51 |
| Stomatitis | 1/4 (25%) | 1 | 5/24 (20.8%) | 5 | 5/25 (20%) | 5 |
| Vomiting | 1/4 (25%) | 1 | 12/24 (50%) | 17 | 12/25 (48%) | 17 |
| General disorders | ||||||
| Face oedema | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Fatigue | 2/4 (50%) | 4 | 4/24 (16.7%) | 10 | 4/25 (16%) | 10 |
| Malaise | 1/4 (25%) | 1 | 9/24 (37.5%) | 11 | 9/25 (36%) | 11 |
| Oedema peripheral | 0/4 (0%) | 0 | 6/24 (25%) | 11 | 6/25 (24%) | 11 |
| Pyrexia | 0/4 (0%) | 0 | 7/24 (29.2%) | 9 | 7/25 (28%) | 9 |
| Infections and infestations | ||||||
| Conjunctivitis | 1/4 (25%) | 1 | 0/24 (0%) | 0 | 0/25 (0%) | 0 |
| Nasopharyngitis | 0/4 (0%) | 0 | 3/24 (12.5%) | 3 | 3/25 (12%) | 3 |
| Upper respiratory tract infection | 1/4 (25%) | 1 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Investigations | ||||||
| Alanine aminotransferase increased | 0/4 (0%) | 0 | 3/24 (12.5%) | 3 | 3/25 (12%) | 3 |
| Aspartate aminotransferase increased | 0/4 (0%) | 0 | 3/24 (12.5%) | 3 | 3/25 (12%) | 3 |
| Blood creatinine increased | 1/4 (25%) | 1 | 6/24 (25%) | 6 | 6/25 (24%) | 6 |
| Creatinine renal clearance decreased | 0/4 (0%) | 0 | 2/24 (8.3%) | 3 | 2/25 (8%) | 3 |
| Neutrophil count decreased | 2/4 (50%) | 7 | 12/24 (50%) | 18 | 13/25 (52%) | 19 |
| Platelet count decreased | 2/4 (50%) | 6 | 4/24 (16.7%) | 5 | 4/25 (16%) | 5 |
| Weight decreased | 0/4 (0%) | 0 | 6/24 (25%) | 10 | 6/25 (24%) | 10 |
| White blood cell count decreased | 2/4 (50%) | 8 | 7/24 (29.2%) | 11 | 8/25 (32%) | 12 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 3/4 (75%) | 9 | 21/24 (87.5%) | 45 | 22/25 (88%) | 46 |
| Dehydration | 0/4 (0%) | 0 | 4/24 (16.7%) | 7 | 4/25 (16%) | 7 |
| Hyperkalaemia | 1/4 (25%) | 1 | 1/24 (4.2%) | 1 | 1/25 (4%) | 1 |
| Hypoalbuminaemia | 0/4 (0%) | 0 | 3/24 (12.5%) | 4 | 3/25 (12%) | 4 |
| Hypokalaemia | 0/4 (0%) | 0 | 4/24 (16.7%) | 4 | 4/25 (16%) | 4 |
| Hyponatraemia | 0/4 (0%) | 0 | 9/24 (37.5%) | 13 | 9/25 (36%) | 13 |
| Hypophosphataemia | 1/4 (25%) | 1 | 0/24 (0%) | 0 | 0/25 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/4 (0%) | 0 | 4/24 (16.7%) | 9 | 4/25 (16%) | 9 |
| Muscular weakness | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Nervous system disorders | ||||||
| Dysgeusia | 1/4 (25%) | 1 | 6/24 (25%) | 8 | 7/25 (28%) | 9 |
| Headache | 1/4 (25%) | 1 | 4/24 (16.7%) | 10 | 4/25 (16%) | 10 |
| Psychiatric disorders | ||||||
| Insomnia | 0/4 (0%) | 0 | 4/24 (16.7%) | 5 | 4/25 (16%) | 5 |
| Renal and urinary disorders | ||||||
| Chromaturia | 0/4 (0%) | 0 | 4/24 (16.7%) | 4 | 4/25 (16%) | 4 |
| Pollakiuria | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Renal impairment | 0/4 (0%) | 0 | 5/24 (20.8%) | 6 | 5/25 (20%) | 6 |
| Reproductive system and breast disorders | ||||||
| Breast pain | 1/4 (25%) | 1 | 0/24 (0%) | 0 | 0/25 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 0/4 (0%) | 0 | 3/24 (12.5%) | 3 | 3/25 (12%) | 3 |
| Hiccups | 3/4 (75%) | 5 | 12/24 (50%) | 22 | 13/25 (52%) | 23 |
| Oropharyngeal pain | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis acneiform | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
| Dry skin | 1/4 (25%) | 1 | 0/24 (0%) | 0 | 0/25 (0%) | 0 |
| Urticaria | 1/4 (25%) | 2 | 0/24 (0%) | 0 | 0/25 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 | 2/25 (8%) | 2 |
Limitations/Caveats
[Not Specified]
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 | Clinical Research (Oncology) |
|---|---|
| Organization | Sumitomo Dainippon Pharmaceutical |
| Phone | e-mail only |
| cc@ds-pharma.co.jp |
Responsible Party:
Sumitomo Pharma Co., Ltd.
ClinicalTrials.gov Identifier:
NCT02347917
Other Study ID Numbers:
- D8807005
First Posted:
Jan 28, 2015
Last Update Posted:
Apr 12, 2022
Last Verified:
Apr 1, 2022