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

Metastatic Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02641873
• Other study ID #: D8809001
• Status: Completed
• Phase: Phase 1
• Start date: December 2015
• Est. completion date: January 2017

Study information

• Verified date: April 2022
• Source: Sumitomo Pharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: January 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East	Kashiwa, Chiba
Japan	Aichi Cancer Center Hospital	Nagoya, Aichi

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of participants with Dose-limiting toxicities (DLT) [Safety and Tolerability]	Safety and tolerability assessed by determination of unacceptable toxicity in patients.	12 months
Primary	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.
Primary	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	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)
Secondary	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