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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

Tracking Information
First Submitted Date  ICMJE June 4, 2015
First Posted Date  ICMJE June 10, 2015
Last Update Posted Date July 21, 2020
Study Start Date  ICMJE August 2015
Actual Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2015)
  • 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 ]
  • Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2015)
  • 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).
  • 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 ]
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers
Official Title  ICMJE A Phase Ib/II Clinical Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors to Adult Patients With Advanced Cancers
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • 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
  • Drug: Nivolumab
    Nivolumab 3 mg/kg is administered as an intravenous infusion over 60 minutes every 14 days.
    Other Name: Opdivo
  • Drug: Pembrolizumab
    Pembrolizumab 2 mg/kg is administered as an intravenous infusion over 30 minutes once every 21 days.
    Other Name: Keytruda
Study Arms  ICMJE
  • Experimental: Combo with Ipilimumab
    Interventions:
    • Drug: BBI608
    • Drug: Ipilimumab
  • Experimental: Combo with Nivolumab
    Interventions:
    • Drug: BBI608
    • Drug: Nivolumab
  • Experimental: Combo with Pembrolizumab
    Interventions:
    • Drug: BBI608
    • 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 Completed
Actual Enrollment  ICMJE
 (submitted: September 12, 2018)
104
Original Estimated Enrollment  ICMJE
 (submitted: June 5, 2015)
120
Actual Study Completion Date  ICMJE June 2020
Actual Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02467361
Other Study ID Numbers  ICMJE BBI608-201CIT
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sumitomo Dainippon Pharma Oncology, Inc
Study Sponsor  ICMJE Sumitomo Dainippon Pharma Oncology, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sumitomo Dainippon Pharma Oncology, Inc
Verification Date July 2020

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