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A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers

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: NCT02467361
Recruitment Status : Completed
First Posted : June 10, 2015
Last Update Posted : July 21, 2020
Sponsor:
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Oncology, Inc

Brief Summary:
This is an open label, multi-center, Phase 1/2 study of BBI608 administered in combination with immunotherapy in adult patients with advanced cancers. The goal of the study is to determine the RP2D of BBI608 in combination with each of the immunotherapeutic agents.

Condition or disease Intervention/treatment Phase
Cancer Drug: BBI608 Drug: Ipilimumab Drug: Nivolumab Drug: Pembrolizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Clinical Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors to Adult Patients With Advanced Cancers
Study Start Date : August 2015
Actual Primary Completion Date : June 2020
Actual Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Combo with Ipilimumab Drug: BBI608
Patients in this trial will receive BBI608 at assigned dose-levels according to the study arm the patient is enrolled into. BBI608 Dose Level 1: 240 mg twice daily, Dose Level 2: 480 mg twice daily. The assigned dose of BBI608 will be administered twice daily with approximately 12 hours between doses.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Drug: Ipilimumab
Ipilimumab 3 mg/kg is administered intravenously over 90 minutes every 21 days for a total of 4 doses.
Other Name: Yervoy

Experimental: Combo with Nivolumab Drug: BBI608
Patients in this trial will receive BBI608 at assigned dose-levels according to the study arm the patient is enrolled into. BBI608 Dose Level 1: 240 mg twice daily, Dose Level 2: 480 mg twice daily. The assigned dose of BBI608 will be administered twice daily with approximately 12 hours between doses.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Drug: Nivolumab
Nivolumab 3 mg/kg is administered as an intravenous infusion over 60 minutes every 14 days.
Other Name: Opdivo

Experimental: Combo with Pembrolizumab Drug: BBI608
Patients in this trial will receive BBI608 at assigned dose-levels according to the study arm the patient is enrolled into. BBI608 Dose Level 1: 240 mg twice daily, Dose Level 2: 480 mg twice daily. The assigned dose of BBI608 will be administered twice daily with approximately 12 hours between doses.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Drug: Pembrolizumab
Pembrolizumab 2 mg/kg is administered as an intravenous infusion over 30 minutes once every 21 days.
Other Name: Keytruda




Primary Outcome Measures :
  1. Determination of the safety and tolerability of BBI608 administered in combination with selected immunotherapeutic agent by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 weeks ]
  2. Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Assessment of the preliminary anti-tumor activity by performing tumor assessments every 8 weeks (Phase 2 portion) [ Time Frame: 6 months ]
    Evaluation of anti-tumor activity will be performed according to Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST).

  2. Pharmacokinetic profile of BBI608 administered in combination with the selected immunotherapeutic agent as assessed by maximum plasma concentration and area under the curve [ Time Frame: -5min, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours on day 1, cycles 1 and 2 ]
  3. Pharmacodynamic activity of BBI608 administered in combination with the selected immunotherapeutic agent as assessed by biomarker analysis [ Time Frame: 6 months ]
    Histopathology and Cancer Stem Cell assays will be performed to provide information of the biomarkers on biopsied patient tumor tissue, and archival samples.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements
  2. A histologically or cytologically confirmed cancer that is metastatic, unresectable, or recurrent and for which treatment with ipilimumab, or nivolumab, or pembrolizumab is a reasonable therapeutic option in the opinion of the investigator.
  3. ≥ 18 years of age
  4. Measurable disease as defined by Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST).
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  6. Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last dose
  7. Females of childbearing potential must have a negative serum pregnancy test
  8. Aspartate transaminase (AST) < 2.5 x upper limit of normal (ULN) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN).
  9. Hemoglobin (Hgb) ≥ 9 g/dl
  10. Total bilirubin ≤ 1.5 × ULN. Patients with liver lesions who do not have hepatocellular carcinoma and who have a total bilirubin < 2.0 x ULN may be eligible if agreed upon by the investigator and medical monitor for the sponsor.
  11. Creatinine ≤ 1.5 × ULN or, for patients with creatinine levels above institutional upper limit of normal, creatinine clearance must be > 60 mL/min/1.73 m^2.
  12. Absolute neutrophil count ≥ 1.5 x 10^9/L
  13. Platelets ≥ 100 x 10^9/L; patients with hepatocellular carcinoma may enroll provided they have a platelet count ≥ 75 x 10^9/L.
  14. Life expectancy ≥ 3 months

Exclusion criteria:

  1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 7 days of first dose of BBI608. Patients may begin BBI608 on a date determined by the investigator and medical monitor for the sponsor after a minimum of 7 days since last receiving anti-cancer treatment, provided that all treatment-related adverse events (AEs) have resolved or have been deemed irreversible
  2. Had a surgical procedure requiring general anesthesia or inpatient hospitalization for recovery less than 4 weeks prior to beginning protocol therapy.
  3. Any known, untreated, brain metastases. Treated subjects must be stable 4 weeks after completion of treatment for brain metastases and image documented stability is required. Patients must have no clinical symptoms from brain metastases and have not required systemic corticosteroids >10 mg/day prednisone or equivalent for at least 2 weeks prior to first dose of study drug.
  4. Pregnant or breastfeeding
  5. Unable or unwilling to swallow BBI608 capsules daily
  6. Significant gastrointestinal disorder(s) (e.g., active Crohn's disease or ulcerative colitis, or a history of extensive gastric resection and/or small intestinal resection) such that absorption of oral medications is impaired.
  7. Has an active autoimmune disease requiring immunosuppression with the exception of subjects with isolated vitiligo, resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave's disease.
  8. Has interstitial lung disease or active, non-infectious pneumonitis
  9. Has a transplanted organ or has undergone allogeneic bone marrow transplant
  10. Has received a live vaccine within 30 days prior to first dose.
  11. Known hypersensitivity to a component of protocol therapy
  12. Uncontrolled concurrent illness including, but not limited to ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or on mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements
  13. Subjects with a history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; c) localized prostate cancer not requiring systemic therapy; and c) other primary tumors with no known active disease present that, in the opinion of the investigator and medical monitor for the sponsor, will not affect patient outcome in the setting of the current diagnosis.
  14. Abnormal ECGs that are clinically significant such as QT prolongation (QTc > 480 msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block or existing left bundle branch block, or signs of new, active ischemia.

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): NCT02467361


Locations
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United States, Colorado
University of Colorado Cancer Center
Denver, Colorado, United States, 80045
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
United States, South Carolina
Institute for Translational Oncology Research
Greenville, South Carolina, United States, 29605
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Sumitomo Dainippon Pharma Oncology, Inc
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Responsible Party: Sumitomo Dainippon Pharma Oncology, Inc
ClinicalTrials.gov Identifier: NCT02467361    
Other Study ID Numbers: BBI608-201CIT
First Posted: June 10, 2015    Key Record Dates
Last Update Posted: July 21, 2020
Last Verified: July 2020
Keywords provided by Sumitomo Dainippon Pharma Oncology, Inc:
Neoplasms
Additional relevant MeSH terms:
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Pembrolizumab
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents