A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma

A Phase I/II Clinical Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma

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).

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.