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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: BBI608; Drug: 5-FU; Drug: Irinotecan; Drug: Levofolinate; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kashiwa, Chiba, Japan
    • National Cancer Center Hospital East
  • Nagoya, Aichi, Japan
    • Aichi Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A histologically confirmed advanced unresectable, metastatic or recurrent colorectal carcinoma
2. Evaluable patient by RECISTversion 1.1
3. Stage IV
4. ≥ 20 years of age
5. Life expectancy ≥ 3 months.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

7. 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]
8. 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
9. Females of childbearing potential have a negative urine pregnancy test
10. 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:

1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or hormone therapy, or heart therapy within 21 days of the first dose of BBI608
2. Major surgery within 28 days prior to first dose
3. Have had a brain metastases with a symptom or requiring treatment
4. Have had coinstantaneously active multiple primary cancer
5. Have had a carcinomatous pleural effusion, ascites, or cardiac effusion requiring treatment
6. Crohn's disease, ulcerative colitis, small intestine resection, diarrhea (watery diarrhea), paralysis intestinal, Intestinal obstruction
7. Gastrointestinal perforation, tracheo-oesophageal fistula, fistula
8. Unable or unwilling to swallow BBI608 capsules
9. Uncontrolled inter-current illness (such as Grade 3 active infection, or serious respiratory disease)
10. Uncontrolled hypertension
11. Patients with recent history of hemoptysis of more than 2.5 mL of red blood within 28days before the enrolment
12. Abnormal ECGs which are clinically significant within 28 days before enrolment
13. Patients who are New York Heart Association (NYHA) functional classes III, or IV, or unstable angina
14. Patients newly expressing angina within three months (90 days) before the enrolment
15. Have had myocardial infarction within six months (180 days)before the enrolment
16. Administrating with antiarrhythmic drug
17. 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
18. Patients of pregnancy or possibility of pregnancy at current time or possibility of pregnancy within 6 months after the last administration of Bevacizumab
19. Have received other investigational products or not finished the assessment in any clinical study within 28 days before enrollment
20. Known severe hypersensitivity to 5-FU/ levofolinate/ irinotecan/Bevacizumab
21. Administration of atazanavir sulfate
22. Prior treatment with BBI608
23. Ineligible for participation in the study in the opinion of the Investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary anti-tumour activity	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.	6 months(an expected average)
Progression Free Survival (PFS)	Participants follow-up for progression free survival will occur. Maximum follow-up time is 12 months after the initial administration of the last subject.	12 months

Collaborators and Investigators

• Sponsor: Sumitomo Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: December 21, 2015
• First Submitted That Met QC Criteria: December 24, 2015
• First Posted (Estimate): December 30, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 9, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: mCRC; metastatic Colorectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Bevacizumab; Leucovorin; Irinotecan; Levoleucovorin
• Other Study ID Numbers: D8809001