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Special Combination of BBI608 and Pembrolizumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02851004
Recruitment Status : Active, not recruiting
First Posted : August 1, 2016
Last Update Posted : November 15, 2019
Sponsor:
Collaborator:
Sumitomo Dainippon Pharma Co., Ltd.
Information provided by (Responsible Party):
Takayuki Yoshino, National Cancer Center Hospital East

Tracking Information
First Submitted Date  ICMJE July 14, 2016
First Posted Date  ICMJE August 1, 2016
Last Update Posted Date November 15, 2019
Actual Study Start Date  ICMJE October 2016
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2019)
  • 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
  • ORR [ Time Frame: 1 year ]
    Objective response rate determined by RECIST version 1.1: for additional cohort to the Phase II part
Original Primary Outcome Measures  ICMJE
 (submitted: July 27, 2016)
Immune-related objective response rate determined by their Response Evaluation Criteria In Solid Tumors (RESIST) [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2019)
  • irPFS [ Time Frame: 12 weeks ]
    Immune-related progression free survival rate at week 12 determined by the irRECIST
  • ORR [ Time Frame: 2 years ]
    Objective response rate determined by RECIST version 1.1: for the Phase II part
  • 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
  • Progression free survival rate at week 12 determined by the RECIST version 1.1 [ Time Frame: 12 weeks ]
    PFS
  • PFS [ Time Frame: 3 years ]
    Progression free survival
  • OS [ Time Frame: 4 years ]
    Overall survival
  • DCR [ Time Frame: 2 years ]
    Disease Control rate
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 4 years ]
    Incidence of adverse events
  • Pharmacokinetic [ Time Frame: 2 months ]
    Area under the blood concentration-time curve (AUC)
  • Pharmacokinetic [ Time Frame: 2 months ]
    CmaxPeak Plasma Concentration (Cmax)
Original Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2016)
  • Immune-related progression free survival rate at week 12 determined by the irRECIST [ Time Frame: 12 weeks ]
  • Objective response rate determined by RECIST version 1.1 [ Time Frame: 2 years ]
  • Progression free survival rate at week 12 determined by the RECIST version 1.1 [ Time Frame: 12 weeks ]
  • Progression free survival [ Time Frame: 3 years ]
  • Overall survival [ Time Frame: 4 years ]
  • Disease control rate [ Time Frame: 2 years ]
  • Incidence of adverse events [ Time Frame: 4 years ]
  • Area under the blood concentration-time curve (AUC) [ Time Frame: 2 months ]
  • Cmax [ Time Frame: 2 months ]
Current Other Pre-specified Outcome Measures
 (submitted: May 17, 2017)
  • 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
  • safety according to immune status [ Time Frame: 3 years ]
    Safety evaluations according to immune status
Original Other Pre-specified Outcome Measures
 (submitted: July 27, 2016)
  • Efficacy evaluations 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 ]
  • Safety evaluations according to immune status [ Time Frame: 3 years ]
 
Descriptive Information
Brief Title  ICMJE Special Combination of BBI608 and Pembrolizumab
Official Title  ICMJE A Phase Ib/II Study of BBI608 in Combination With Pembrolizumab in Patients With Metastatic Colorectal Cancer
Brief Summary the efficacy and safety of BBI608 in combination with pembrolizumab
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

[Phase Ib] 6 to 9 patients

[Phase II] Cohort A (MSI-H): 10 patients Cohort B (MSS): 40 patients Including patients with metastatic CRC treated at the recommended dose (RD) level in the Phase Ib part who meet criteria for the full analysis set (FAS)

[Additional cohort to the Phase II part]

  1. st stage: CMS 1 or 4, MSS right-side colon cancers*: 10 patients
  2. nd stage:

    1. : If no patient shows a partial or complete response in the 1st stage, the study will be prematurely terminated.
    2. : If 1 or 2 patients show a partial or complete response in the 1st stage, 19 patients with CMS 1 or 4, MSS right-side colon cancers will be enrolled additionally.
    3. : If 3 or more patients show a partial or complete response in the 1st stage, 19 patients with CMS 1 or 4, MSS right-side colon cancers and 10 patients with CMS 1 or 4, MSS left-side colon cancers* will be enrolled additionally.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: BBI608(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.

  • Drug: 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.

Study Arms  ICMJE Experimental: BBI608 + Pembrolizumab
BBI608 and Pembrolizumab
Interventions:
  • Drug: BBI608(Napabucasin)
  • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 13, 2019)
94
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2016)
56
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02851004
Other Study ID Numbers  ICMJE EPOC1503
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Takayuki Yoshino, National Cancer Center Hospital East
Study Sponsor  ICMJE Takayuki Yoshino
Collaborators  ICMJE Sumitomo Dainippon Pharma Co., Ltd.
Investigators  ICMJE
Study Chair: Takayuki Yoshino, Dr National Cancer Center Hospital East
PRS Account National Cancer Center Hospital East
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP