Clinical trial NCT02347917: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malignant Pleural Mesothelioma
Non-Small Cell Lung Cancer
Lead sponsor: Sumitomo Pharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-01-28
Enrollment: 28
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs)
timeFrame: Between initial dosing of the investigational drug and final evaluation in the follow-up observation period, about 17 months
measure: Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: From Day 1 of Cycle 1 to Day 24 pre-dose examination (23 days)
measure: Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP
timeFrame: Cycle 1 Day 1 (Cmax only) and Day 23
measure: Phase 1 Part: Area Under the Concentration-time Curve
timeFrame: Cycle 1 Day 1 and Day 23
measure: Phase 2 Part: Progression-free Survival (PFS)
timeFrame: From BBI608 administration to documented PD or death, whichever is earlier, about 17 months
Secondary outcomes:
measure: Best Overall Response
timeFrame: Every 6 weeks from the first dose of BBI608 until Week 30, and every 9 weeks from Week 31.
measure: Response Rate (RR) and Disease Control Rate (DCR)
timeFrame: From BBI608 administration to death from any cause, about 17 months
measure: Overall Survival(OS)
timeFrame: From BBI608 administration to death from any cause, up to 31 months
measure: Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC])
timeFrame: 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]
measure: Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1])
timeFrame: 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]
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
Study officials:
affiliation: Sumitomo Pharma Co., Ltd.
name: Sumitomo Pharma Co., Ltd. Japan
role: STUDY_DIRECTOR
References: