Phase 2
N=28
A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma
Malignant Pleural Mesothelioma · Non-Small Cell Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02347917 ↗Enrolled (actual)
28
Serious AEs
26.4%
Results posted
Oct 2021
Primary outcome: Primary: Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) — 4; 0; 0; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- BBI608 (Drug); Pemetrexed (Drug); Cisplatin (Drug)
- Age
- Adult, Older Adult · 20+ yrs
- Sex
- All
- Sponsor
- Sumitomo Pharma Co., Ltd.
- Primary completion
- May 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) |
4; 0; 0; 1; 1; 0 | — |
| PRIMARY Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs) |
— | — |
| PRIMARY Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP |
307.5; 473.7; 196.1 | — |
| PRIMARY Phase 1 Part: Area Under the Concentration-time Curve |
1814.3; 2223.8; 2413.5; 3797.0; 6103.7; 10762.7 | — |
| PRIMARY Phase 2 Part: Progression-free Survival (PFS) |
5.59; 5.59 | — |
| SECONDARY Best Overall Response |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Response Rate (RR) and Disease Control Rate (DCR) |
0; 0; 0; 8; 8; 3 | — |
| SECONDARY Overall Survival(OS) |
19.81; 30.1; NA; 12.14; 12.75 | — |
| SECONDARY Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) |
70.0; 70.0; 30.0; 30.0; 110.0; 110.0 | — |
| SECONDARY Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) |
0.160; 0.160; 0.050; 0.050; 0.070; 0.070 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02347917). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.