A Study of BBI608 Administrated With FOLFIRI + Bevacizumab in Adult Patients With Metastatic Colorectal Cancer

NCT02641873 | Completed Phase 1

• 1 other identifier: D8809001
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, multicenter, phase 1 study of BBI608 in combination with FOLFIRI + Bavacizumab. This study population is adult Japanese patients with metastatic colorectal cancers in FOLFIRI + Bevacizumab combination therapy.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic Colorectal Cancer; mCRC

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events (AEs), serious adverse events (SAEs) [Safety and Tolerability]

  Safety and tolerability assessed by adverse events (AEs), serious adverse events (SAEs)

  12 months

• Number of participants with Dose-limiting toxicities (DLT) [Safety and Tolerability]

  Safety and tolerability assessed by determination of unacceptable toxicity in patients.

  12 months

• Cmax (Peak plasma concentration)

  Cmax (Peak plasma concentration)

  Day 1: prior to BBI608 and 2,4,6,8,10,12,24 hours after the first dose.

• AUC0-24h (Area under the plasma concentration versus time curve)

  AUC0-24h (Area under the plasma concentration versus time curve)

  Day 1: prior to BBI608 and 2,4,6,8,10,12,24 hours after the first dose.

Secondary Outcomes (2)

• Preliminary anti-tumour activity

  6 months(an expected average)

• Progression Free Survival (PFS)

  12 months

Study Arms (1)

BBI608 + FOLFIRI +Bevacizumab

EXPERIMENTAL

Drug: BBI608; Drug: 5-FU; Drug: Irinotecan; Drug: Levofolinate; Drug: Bevacizumab

Interventions

BBI608 DRUG

240 mg twice daily (480 mg total daily dose)

BBI608 + FOLFIRI +Bevacizumab

5-FU DRUG

400 mg/m2 bolus will be administered intravenously immediately following irinotecan/levofolinate infusion, followed by 1200 mg/m2/day (total 2400 mg/m2) continuous infusion per cycle(14 days).

BBI608 + FOLFIRI +Bevacizumab

Irinotecan DRUG

180 mg/m2 together with levofolinate will be administered intravenously per cycle(14 days).

BBI608 + FOLFIRI +Bevacizumab

Levofolinate DRUG

200 mg/m2 together with Irinotecan will be administered intravenously per cycle(14 days).

BBI608 + FOLFIRI +Bevacizumab

Bevacizumab DRUG

5 mg/kg will be administered intravenously following irinotecan/levofolinate infusion per cycle(14 days).

BBI608 + FOLFIRI +Bevacizumab

Eligibility Criteria

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

You may qualify if:

• A histologically confirmed advanced unresectable, metastatic or recurrent colorectal carcinoma
• Evaluable patient by RECISTversion 1.1
• Stage IV
• ≥ 20 years of age
• Life expectancy ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Patients with following organ function within 14 days before enrollment (on the basis of the most recent data during the period if multiple data are available)
• Hemoglobin (Hg) ≥ 9.0 g/dL
• Neutrophil count ≥ 1.5 x 103/μL
• Platelet count ≥ 10 x 104/μL
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × institutional upper limit of normal (ULN) \[≤ 5 × ULN in presence of liver metastases \]
• Total bilirubin ≤ 1.5 × institutional ULN \[≤ 2 × ULN in presence of liver metastases \]
• Creatinine ≤ 1.5 × institutional ULN
• Proteinuria by dipstick urine analysis ≤ 1+. \[ UPCR (Urine Albumin-to-Creatinine Ratio) ≤ 1, or protein volume of 24-hour urine collection ≤ 1 g, in the case of patients with a 2+ urine dipstick reading\]
• For 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 or 6 months after Bevacizumab treatment.. For male patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 90 days after the last protocol treatment dose or 6 months after Bevacizumab treatment

You may not qualify if:

• Anti-cancer chemotherapy, radiotherapy, immunotherapy, or hormone therapy, or heart therapy within 21 days of the first dose of BBI608
• Major surgery within 28 days prior to first dose
• Have had a brain metastases with a symptom or requiring treatment
• Have had coinstantaneously active multiple primary cancer
• Have had a carcinomatous pleural effusion, ascites, or cardiac effusion requiring treatment
• Crohn's disease, ulcerative colitis, small intestine resection, diarrhea (watery diarrhea), paralysis intestinal, Intestinal obstruction
• Gastrointestinal perforation, tracheo-oesophageal fistula, fistula
• Unable or unwilling to swallow BBI608 capsules
• Uncontrolled inter-current illness (such as Grade 3 active infection, or serious respiratory disease)
• Uncontrolled hypertension
• Patients with recent history of hemoptysis of more than 2.5 mL of red blood within 28days before the enrolment
• Abnormal ECGs which are clinically significant within 28 days before enrolment
• Patients who are New York Heart Association (NYHA) functional classes III, or IV, or unstable angina
• Patients newly expressing angina within three months (90 days) before the enrolment
• Have had myocardial infarction within six months (180 days)before the enrolment

Sponsors & Collaborators

• Sumitomo Pharma Co., Ltd.: lead

Study Sites (2)

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Location

Aichi Cancer Center Hospital

Nagoya, Aichi, Japan

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

napabucasin; Fluorouracil; Irinotecan; Leucovorin; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: December 21, 2015
• First Posted: December 30, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: January 1, 2017
• Last Updated: April 12, 2022

Record last verified: 2022-04

Locations

JP (2)