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

NCT02347917 | Completed Phase 1 Results

• 1 other identifier: D8807005
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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).

Conditions

Malignant Pleural Mesothelioma; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• 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

  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

  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

  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

  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.

  From BBI608 administration to documented PD or death, whichever is earlier, about 17 months

Secondary Outcomes (5)

• Best Overall Response

  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)

  From BBI608 administration to death from any cause, about 17 months

• Overall Survival(OS)

  From BBI608 administration to death from any cause, up to 31 months

• Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC])

  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])

  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]

Study Arms (1)

BBI608 puls pemetrexed and cisplatin

EXPERIMENTAL

Drug: BBI608; Drug: Pemetrexed; Drug: Cisplatin

Interventions

BBI608 DRUG

480 mg orally twice daily (960 mg total daily dose)

BBI608 puls pemetrexed and cisplatin

Pemetrexed DRUG

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).

BBI608 puls pemetrexed and cisplatin

Cisplatin DRUG

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).

BBI608 puls pemetrexed and cisplatin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sumitomo Pharma Co., Ltd.: lead

Study Sites (2)

National Cancer Center Hospital East

Chiba, Japan

Location

National Cancer Center Hospital

Tokyo, Japan

Location

MeSH Terms

Conditions

Mesothelioma, Malignant; Carcinoma, Non-Small-Cell Lung

Interventions

napabucasin; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Clinical Research (Oncology)
• Organization: Sumitomo Dainippon Pharmaceutical

cc@ds-pharma.co.jp

e-mail only

Study Officials

• Sumitomo Pharma Co., Ltd. Japan

  Sumitomo Pharma Co., Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2015
• First Posted: January 28, 2015
• Study Start: February 1, 2015
• Primary Completion: May 31, 2018
• Study Completion: May 31, 2018
• Last Updated: April 12, 2022
• Results First Posted: October 1, 2021

Record last verified: 2022-04

Locations

JP (2)