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Special Combination of BBI608 and Pembrolizumab

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ClinicalTrials.gov Identifier: NCT02851004
Recruitment Status : Recruiting
First Posted : August 1, 2016
Last Update Posted : May 19, 2017
Sponsor:
Collaborator:
Sumitomo Dainippon Pharma Co., Ltd.
Information provided by (Responsible Party):
Takayuki Yoshino, National Cancer Center Hospital East

Brief Summary:
the efficacy and safety of BBI608 in combination with pembrolizumab

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: BBI608(Napabucasin) Drug: Pembrolizumab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of BBI608 in Combination With Pembrolizumab in Patients With Metastatic Colorectal Cancer
Study Start Date : October 2016
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BBI608 + Pembrolizumab
BBI608 and Pembrolizumab
Drug: BBI608(Napabucasin)

1 cycle is 21days.

BBI608: Oral administration at a dose of 240mg or 480 mg twice daily (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

The therapy will be repeated until meeting the discontinuation criteria.





Primary Outcome Measures :
  1. irORR [ Time Frame: 2 years ]
    Immune-related objective response rate determined by their Response Evaluation Criteria In Solid Tumors (RESIST)


Secondary Outcome Measures :
  1. irPFS [ Time Frame: 12 weeks ]
    Immune-related progression free survival rate at week 12 determined by the irRECIST

  2. ORR [ Time Frame: 2 years ]
    Objective response rate determined by RECIST version 1.1

  3. Progression free survival rate at week 12 determined by the RECIST version 1.1 [ Time Frame: 12 weeks ]
    PFS

  4. PFS [ Time Frame: 3 years ]
    Progression free survival

  5. OS [ Time Frame: 4 years ]
    Overall survival

  6. DCR [ Time Frame: 2 years ]
    Disease Control rate

  7. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 4 years ]
    Incidence of adverse events

  8. Pharmacokinetic [ Time Frame: 2 months ]
    Area under the blood concentration-time curve (AUC)

  9. Pharmacokinetic [ Time Frame: 2 months ]
    CmaxPeak Plasma Concentration (Cmax)


Other Outcome Measures:
  1. 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

  2. safety according to immune status [ Time Frame: 3 years ]
    Safety evaluations according to immune status



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  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
  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) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02851004


Contacts
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Contact: Yasutoshi Kuboki, Dr +81-4-7133-1111 ext 91400 scoop_core@east.ncc.go.jp
Contact: Akihito Kawazoe, Dr +81-4-7133-1111 ext 91558 scoop_core@east.ncc.go.jp

Locations
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Japan
National Cancer Center Hospital East Recruiting
Kashiwa, Chiba, Japan, 277-8577
Contact: Yasutoshi Kuboki, MD    +81-4-7133-1111 ext 91400    scoop_core@east.ncc.go.jp   
Sponsors and Collaborators
Takayuki Yoshino
Sumitomo Dainippon Pharma Co., Ltd.
Investigators
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Study Chair: Takayuki Yoshino, Dr National Cancer Center Hospital East

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Responsible Party: Takayuki Yoshino, Director of Gastrointestinal Oncology Division, National Cancer Center Hospital East
ClinicalTrials.gov Identifier: NCT02851004     History of Changes
Other Study ID Numbers: EPOC1503
First Posted: August 1, 2016    Key Record Dates
Last Update Posted: May 19, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents