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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
480 mg orally twice daily (960 mg total daily dose)
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).
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).
National Cancer Center Hospital East
Chiba, Japan
National Cancer Center Hospital
Tokyo, Japan
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
Time frame: Between initial dosing of the investigational drug and final evaluation in the follow-up observation period, about 17 months
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: 1. Inappetence, nausea, vomiting and electrolyte abnormality which, within 3 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment 2. 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)
Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Cycle 1 Day 1 (Cmax only) and Day 23
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
Time frame: Cycle 1 Day 1 and Day 23
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.
Time frame: From BBI608 administration to documented PD or death, whichever is earlier, about 17 months
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.
Time frame: Every 6 weeks from the first dose of BBI608 until Week 30, and every 9 weeks from Week 31.
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.
Time frame: From BBI608 administration to death from any cause, about 17 months
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.
Time frame: From BBI608 administration to death from any cause, up to 31 months
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]
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]