Back to resultsA Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma
Primary Purpose
Malignant Pleural Mesothelioma, Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
BBI608
Pemetrexed
Cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Pleural Mesothelioma
Eligibility Criteria
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.
Sites / Locations
- National Cancer Center Hospital East
- National Cancer Center Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BBI608 puls pemetrexed and cisplatin
Arm Description
Outcomes
Primary Outcome Measures
Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs)
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)
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
Phase 1 Part: Area Under the Concentration-time Curve
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)
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
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)
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)
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])
Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1])
Full Information
NCT ID
NCT02347917
First Posted
January 21, 2015
Last Updated
April 9, 2022
Sponsor
Sumitomo Pharma Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02347917
Brief Title
A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma
Official Title
A Phase I/II Clinical Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
May 31, 2018 (Actual)
Study Completion Date
May 31, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sumitomo Pharma Co., Ltd.
4. Oversight
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma, Non-Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BBI608 puls pemetrexed and cisplatin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BBI608
Intervention Description
480 mg orally twice daily (960 mg total daily dose)
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
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).
Primary Outcome Measure Information:
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
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)
Title
Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP
Time Frame
Cycle 1 Day 1 (Cmax only) and Day 23
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
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
Secondary Outcome Measure Information:
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.
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
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
Title
Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC])
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]
Title
Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1])
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]
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sumitomo Pharma Co., Ltd. Japan
Organizational Affiliation
Sumitomo Pharma Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
National Cancer Center Hospital East
City
Chiba
Country
Japan
Facility Name
National Cancer Center Hospital
City
Tokyo
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma
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