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

Sponsor

Sumitomo Pharma Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT02641873

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: BBI608 Drug: 5-FU Drug: Irinotecan Drug: Levofolinate Drug: Bevacizumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of BBI608 Administered With FOLFIRI + Bevacizumab in Adult Patients With Metastatic Colorectal Cancer

Study Start Date :

Dec 1, 2015

Actual Primary Completion Date :

Dec 1, 2016

Actual Study Completion Date :

Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BBI608 + FOLFIRI +Bevacizumab	Drug: BBI608 240 mg twice daily (480 mg total daily dose) Drug: 5-FU 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). Drug: Irinotecan 180 mg/m2 together with levofolinate will be administered intravenously per cycle(14 days). Drug: Levofolinate 200 mg/m2 together with Irinotecan will be administered intravenously per cycle(14 days). Drug: Bevacizumab 5 mg/kg will be administered intravenously following irinotecan/levofolinate infusion per cycle(14 days).

Arm

Intervention/Treatment

Experimental: BBI608 + FOLFIRI +Bevacizumab

Drug: BBI608

240 mg twice daily (480 mg total daily dose)

Drug: 5-FU

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).

Drug: Irinotecan

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

Drug: Levofolinate

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

Drug: Bevacizumab

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

Outcome Measures

Primary Outcome Measures

Incidence of adverse events (AEs), serious adverse events (SAEs) [Safety and Tolerability] [12 months]
Safety and tolerability assessed by adverse events (AEs), serious adverse events (SAEs)
Number of participants with Dose-limiting toxicities (DLT) [Safety and Tolerability] [12 months]
Safety and tolerability assessed by determination of unacceptable toxicity in patients.
Cmax (Peak plasma concentration) [Day 1: prior to BBI608 and 2,4,6,8,10,12,24 hours after the first dose.]
Cmax (Peak plasma concentration)
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.]
AUC0-24h (Area under the plasma concentration versus time curve)

Secondary Outcome Measures

Preliminary anti-tumour activity [6 months(an expected average)]
The radiologic assessments will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST for patients with metastatic colorectal cancer.
Progression Free Survival (PFS) [12 months]
Participants follow-up for progression free survival will occur. Maximum follow-up time is 12 months after the initial administration of the last subject.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
Females of childbearing potential have a negative urine pregnancy test
Patients who have provided written voluntary consent in person to participate in this study after fully receiving and understanding the information about this study, including study

Exclusion Criteria:

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
Administrating with antiarrhythmic drug
Patients who are planning to breast-feeding by whichever 30 days after the last administration of BBI608 or by 6 months after the last administration of Bevacizumab
Patients of pregnancy or possibility of pregnancy at current time or possibility of pregnancy within 6 months after the last administration of Bevacizumab
Have received other investigational products or not finished the assessment in any clinical study within 28 days before enrollment
Known severe hypersensitivity to 5-FU/ levofolinate/ irinotecan/Bevacizumab
Administration of atazanavir sulfate
Prior treatment with BBI608
Ineligible for participation in the study in the opinion of the Investigators