Clinical Trials /

A Study of BBI608 in Adult Patients With Advanced Colorectal Cancer

NCT01776307

Description:

This is an open label, multi-center, Phase 2 study of BBI608 in combination with cetuximab, panitumumab or capecitabine in patients with advanced colorectal cancer.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:A Study of BBI608 in Adult Patients With Advanced Colorectal Cancer
  • Official Title:A Phase II Clinical Study of BBI608 in Adult Patients With Advanced Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: BBI608-224
  • NCT ID: NCT01776307

Trial Conditions

  • Colorectal Cancer

Trial Interventions

DrugSynonymsArms
BBI608Napabucasin, BB608, BBI-608BBI608 in combination with cetuximab
PanitumumabVectibixBBI608 in combination with panitumumab
CapecitabineXelodaBBI608 in combination with capecitabine
CetuximabErbituxBBI608 in combination with cetuximab

Trial Purpose

This is an open label, multi-center, Phase 2 study of BBI608 in combination with cetuximab, panitumumab or capecitabine in patients with advanced colorectal cancer.

Detailed Description

This is an open label, multi-center, Phase 2 study of BBI608 administered in combination with either cetuximab, or panitumumab, or capecitabine. A cycle will consist of daily and continuous oral administration of BBI608 for four weeks in combination with either cetuximab, or panitumumab, or capecitabine.

Trial Arms

NameTypeDescriptionInterventions
BBI608 in combination with cetuximabExperimental
  • BBI608
      • Cetuximab
BBI608 in combination with panitumumabExperimental
  • BBI608
  • Panitumumab
    BBI608 in combination with capecitabineExperimental
    • BBI608
      • Capecitabine

      Eligibility Criteria

      Inclusion Criteria:

      - Signed written informed consent must be obtained and documented according to International Conference on Harmonization (ICH), Good Clinical Practice(GCP), the local regulatory requirements, and permission to use private health information in accordance with the Health Insurance Portability and Accountability Act (HIPPA) prior to study-specific screening procedures.

      - A histologically or cytologically confirmed colorectal cancer that is metastatic, unresectable, or recurrent.

      - Patients must have received at least 2 regimens containing 5-Fluorouracil,oxaliplatin, or irinotecan.

      - Patients to be enrolled in the Cetuximab or Panitumumab combination arms must have colorectal cancer which is K-Ras wild-type.

      - ≥ 18 years of age.

      - Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

      - Karnofsky performance Status ≥ 70%

      - 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 BBI608 dose.

      - Females of childbearing potential must have a negative serum pregnancy test.

      - Aspartate transaminase (AST) and alanine transaminase (ALT) ≤1.5 × upper limit of normal(ULN), or ≤ 2.5 × ULN with metastatic liver disease.

      - Hemoglobin (Hgb) ≥ 10 g/dl.

      - Total bilirubin ≤ 1.5 × ULN.

      - Creatinine ≤ 1.5 × ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.

      - Absolute neutrophil count ≥ 1.5 x 10^9/L.

      - Platelets ≥ 100 x 10^9/L.

      - Life expectancy ≥ 3 months.

      Exclusion Criteria:

      - Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks of first dose with the exception for a single dose radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before beginning the administration of BBI608.

      - Surgery within 4 weeks prior to first dose.

      - Any known symptomatic brain metastases requiring steroids. Patients with treated brain metastases must be stable for 4 weeks after completion of that treatment, with image documentation required. Patients must have no clinical symptoms from brain metastases and must be either off steroids or on a stable dose of steroids for at least 2 weeks prior to protocol enrollment. Patients with known leptomeningeal metastases are excluded, even if treated.

      - Pregnant or breastfeeding

      - Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection)

      - Unable or unwilling to swallow BBI608 capsules daily.

      - Uncontrolled intercurrent 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 mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.

      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Both
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Disease Control Rate
      Time Frame:8 weeks
      Safety Issue:No
      Description:Assessment of Disease Control Rate, defined as the proportion of patients with a documented complete response, partial response and stable disease based on RECIST, in patients with advanced colorectal cancer given BBI608 in combination with cetuximab, panitumumab or capecitabine

      Secondary Outcome Measures

      Measure:Overall Survival
      Time Frame:From date of randomization until the date of death, assessed up to 100 months
      Safety Issue:No
      Description:Assessment of Overall Survival in patients with advanced colorectal cancer given BBI608 in combination with cetuximab, panitumumab or capecitabine
      Measure:Progression Free Survival
      Time Frame:From date of randomization until the date of first documented progression or death, whichever comes first, assessed up to 100 months
      Safety Issue:No
      Description:Assessment of Progression Free Survival in patients with advanced colorectal cancer given BBI608 in combination with cetuximab, panitumumab or capecitabine by performing tumor assessments every 8 weeks.
      Measure:Safety
      Time Frame:Adverse events will be assessed at baseline, while the participant is taking BBI608, and for 30 days after stopping therapy. The average length of this duration is expected to be approximately 4 months.
      Safety Issue:Yes
      Description:Assessment of safety of BBI608 given in combination with cetuximab, panitumumab or capecitabine to patients with advanced colorectal cancer by reporting of adverse events and serious adverse events
      Measure:Pharmacokinetics
      Time Frame:On Day 5 and Day 26 in the cetuximab combination arm; on Day 8 and 22 in the panitumumab combination arm; and on Day 8 and 21 in the capecitabine combination arm
      Safety Issue:No
      Description:Observe the area under the plasma concentration versus time curve of BBI608 in combination with cetuximab, BBI608 in combination with panitumumab, and BBI608 in combination with capecitabine
      Measure:Pharmacodynamics
      Time Frame:At baseline and at 4 hours after administration of BBI608 morning dose on Day 8
      Safety Issue:No
      Description:Pharmacodynamic assessments to analyze biomarkers in tumor tissues will be performed in patients when tumor biopsy with a minimally invasive procedure is deemed possible by Investigator.

      Trial Keywords

      • BBI608