Special Combination of BBI608 and Pembrolizumab

Metastatic Colorectal Cancer Clinical Trial

Official title:

A Phase Ib/II Study of BBI608 in Combination With Pembrolizumab in Patients With Metastatic Colorectal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02851004
• Other study ID #: EPOC1503
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 2016
• Est. completion date: August 23, 2021

Study information

• Verified date: August 2021
• Source: National Cancer Center Hospital East
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

the efficacy and safety of BBI608 in combination with pembrolizumab

Description:

This is a multicenter, open-label Phase Ib/II study to exploratively evaluate the efficacy and safety of BBI608 in combination with pembrolizumab in patients with metastatic colorectal cancer (CRC) not responded to or intolerant of standard chemotherapy.The same analysis will be performed for the additional cohort to the Phase II part, consisting of patients with metastatic CMS 1 or 4, MMS, CRC not responsive to or intolerant of standard chemotherapy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 55
• Est. completion date: August 23, 2021
• Est. primary completion date: February 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

For the additional cohort to the Phase II part, screening tests will be performed to identify CMS 1 or 4 and MSS before obtaining informed consent.

Patients, who meet all of the following inclusion criteria and none of the exclusion criteria, are eligible for enrollment in the study.

Inclusion Criteria

1. Patients who personally provided written consent to be the subjects of the study

2. Age of 20 years or older on the day of informed consent

3. [Phase Ib] Histologically confirmed gastrointestinal cancer

[Phase II] Histologically confirmed colon or rectal cancer that is adenocarcinoma , and identification of at least the KRAS codon 12 and 13 mutation status determined by RAS gene testing. Confirmation of the microsatellite instability (MSI) status.

[Additional cohort to the Phase II part] Histologically confirmed colon or rectal cancer that is adenocarcinoma, and identification of RAS mutation status. Identification of CMS 1 or 4 and MSS by screening tests.

4. [Phase Ib] Gastrointestinal cancer not responded to or intolerant of standard chemotherapy

[Phase II]A history of treatment with one or more regimens of the following standard chemotherapies for metastatic CRC, and being not responded to or tolerated the chemotherapies

[Additional cohort to the Phase II part] In accordance with Cohort B in the Phase II part.

5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

6. Patients with evaluable lesions (Cohort A in Phase II and Phase Ib) or measurable lesions (Cohort B in Phase II and the additional cohort to the Phase II part) specified in the RECIST version 1.1

7. Patients with adequate organ function based on the following laboratory values measured within 7 days before enrollment

8. Women of childbearing potential who are negative in a pregnancy test within 7 days before enrollment. Both male and female patients who consent to practice appropriate contraception during the study and for 4 months after the discontinuation of the protocol treatment

9. Patients with an expected survival of at least 3 months

Exclusion criteria

1. Patients who received chemotherapy, molecular-targeted agents and/or palliative radiotherapy within 2 weeks before the start of the protocol treatment or have not recovered from toxicity caused by previous treatment

2. Patients who underwent general anesthesia, surgery requiring hospitalization and extensive radiotherapy within 4 weeks before the start of the protocol treatment or minor surgery such as implantation of a central venous access device within two weeks before the start of the protocol treatment

3. Patients with active central nervous system metastases or carcinomatous meningitis.

4. Pregnant or lactating women

5. Patients who are unable or not willing to take BBI608 capsules every day

6. Patients with gastrointestinal disease markedly interfering with the absorption of oral formulations as judged by the investigator

7. Patients with active autoimmune disease requiring systemic treatment within 2 years before the start of the protocol treatment.

8. Patients with a history or signs of interstitial lung disease or active non-infectious pneumonitis

9. Patients who underwent organ or bone marrow transplantation

10. Patients who received a live vaccine within 30 days before the start of the protocol treatment

11. Patients who participated in another clinical study within 4 weeks before the start of the protocol treatment and used or using an investigational drug or device

12. Patients who previously received immunotherapy with drugs targeting PD-1, PD-L1 and/or PD-L2 or BBI608 therapy, or took part in a clinical study of pembrolizumab or BBI608

13. Patients with uncontrollable complications

14. Patients with a history of other malignancies within 3 years before the start of the protocol treatment.

15. Patients with clinically significant Electrocardiogram (ECG) abnormalities

16. Patients with a history of Human Immunodeficiency Virus (HIV)

17. Patients with active hepatitis B or C

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Napabucasin
1 cycle is 21days. BBI608: Oral administration at a dose of 240mg or 480 mg twice daily (BID), every day. [Additional cohort to the Phase II part] Oral administration at a dose of 240mg mg BID, every day The therapy will be repeated until meeting the discontinuation criteria.
• Pembrolizumab
1 cycle is 21days. Pembrolizumab: Administration at a dose of 200 mg/body on Day 1 of each cycle [Additional cohort to the Phase II part] Administration at a dose of 200 mg/body on Day 1 of each cycle. The therapy will be repeated until meeting the discontinuation criteria.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Takayuki Yoshino	Sumitomo Dainippon Pharma Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	efficacy according to immune status - Immune status will be analyzed using biopsy and blood samples by flow cytometry, RNA seq, whole exome sequencing, and immunohistochemistry etc.	Efficacy evaluations according to immune status	3 years
Other	safety according to immune status	Safety evaluations according to immune status	3 years
Primary	irORR	Immune-related objective response rate determined by their Response Evaluation Criteria In Solid Tumors (RESIST): for the Phase II part	2 years
Primary	ORR	Objective response rate determined by RECIST version 1.1: for additional cohort to the Phase II part	1 year
Secondary	irPFS	Immune-related progression free survival rate at week 12 determined by the irRECIST	12 weeks
Secondary	ORR	Objective response rate determined by RECIST version 1.1: for the Phase II part	2 years
Secondary	irORR	Immune-related objective response rate determined by their Response Evaluation Criteria In Solid Tumors (RESIST): for additional cohort to the Phase II part	1 year
Secondary	Progression free survival rate at week 12 determined by the RECIST version 1.1	PFS	12 weeks
Secondary	PFS	Progression free survival	3 years
Secondary	OS	Overall survival	4 years
Secondary	DCR	Disease Control rate	2 years
Secondary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Incidence of adverse events	4 years
Secondary	Pharmacokinetic	Area under the blood concentration-time curve (AUC)	2 months
Secondary	Pharmacokinetic	CmaxPeak Plasma Concentration (Cmax)	2 months