- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02851004
Special Combination of BBI608 and Pembrolizumab
A Phase Ib/II Study of BBI608 in Combination With Pembrolizumab in Patients With Metastatic Colorectal Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Chiba
-
Kashiwa, Chiba, Japan, 277-8577
- National Cancer Center Hospital East
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- Patients who personally provided written consent to be the subjects of the study
- Age of 20 years or older on the day of informed consent
[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.
[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.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
- 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
- Patients with adequate organ function based on the following laboratory values measured within 7 days before enrollment
- 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
- Patients with an expected survival of at least 3 months
Exclusion criteria
- 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
- 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
- Patients with active central nervous system metastases or carcinomatous meningitis.
- Pregnant or lactating women
- Patients who are unable or not willing to take BBI608 capsules every day
- Patients with gastrointestinal disease markedly interfering with the absorption of oral formulations as judged by the investigator
- Patients with active autoimmune disease requiring systemic treatment within 2 years before the start of the protocol treatment.
- Patients with a history or signs of interstitial lung disease or active non-infectious pneumonitis
- Patients who underwent organ or bone marrow transplantation
- Patients who received a live vaccine within 30 days before the start of the protocol treatment
- 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
- 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
- Patients with uncontrollable complications
- Patients with a history of other malignancies within 3 years before the start of the protocol treatment.
- Patients with clinically significant Electrocardiogram (ECG) abnormalities
- Patients with a history of Human Immunodeficiency Virus (HIV)
- Patients with active hepatitis B or C
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BBI608 + Pembrolizumab
BBI608 and Pembrolizumab
|
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. 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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
irORR
Time Frame: 2 years
|
Immune-related objective response rate determined by their Response Evaluation Criteria In Solid Tumors (RESIST): for the Phase II part
|
2 years
|
ORR
Time Frame: 1 year
|
Objective response rate determined by RECIST version 1.1: for additional cohort to the Phase II part
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
irPFS
Time Frame: 12 weeks
|
Immune-related progression free survival rate at week 12 determined by the irRECIST
|
12 weeks
|
ORR
Time Frame: 2 years
|
Objective response rate determined by RECIST version 1.1: for the Phase II part
|
2 years
|
irORR
Time Frame: 1 year
|
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
|
Progression free survival rate at week 12 determined by the RECIST version 1.1
Time Frame: 12 weeks
|
PFS
|
12 weeks
|
PFS
Time Frame: 3 years
|
Progression free survival
|
3 years
|
OS
Time Frame: 4 years
|
Overall survival
|
4 years
|
DCR
Time Frame: 2 years
|
Disease Control rate
|
2 years
|
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 4 years
|
Incidence of adverse events
|
4 years
|
Pharmacokinetic
Time Frame: 2 months
|
Area under the blood concentration-time curve (AUC)
|
2 months
|
Pharmacokinetic
Time Frame: 2 months
|
CmaxPeak Plasma Concentration (Cmax)
|
2 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: 3 years
|
Efficacy evaluations according to immune status
|
3 years
|
safety according to immune status
Time Frame: 3 years
|
Safety evaluations according to immune status
|
3 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Takayuki Yoshino, Dr, National Cancer Center Hospital East
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Pembrolizumab
Other Study ID Numbers
- EPOC1503
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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