Clinical Trials /

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

NCT02467361

Description:

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.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers
  • Official Title: A Phase Ib/II Clinical Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors to Adult Patients With Advanced Cancers

Clinical Trial IDs

  • ORG STUDY ID: BBI608-201CIT
  • NCT ID: NCT02467361

Conditions

  • Cancer

Interventions

DrugSynonymsArms
BBI608Napabucasin, BB608, BBI-608Combo with Ipilimumab
IpilimumabYervoyCombo with Ipilimumab
NivolumabOpdivoCombo with Nivolumab
PembrolizumabKeytrudaCombo with Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Combo with IpilimumabExperimental
  • BBI608
  • Ipilimumab
Combo with NivolumabExperimental
  • BBI608
  • Nivolumab
Combo with PembrolizumabExperimental
  • BBI608
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Assessment of the preliminary anti-tumor activity by performing tumor assessments every 8 weeks (Phase 2 portion)
Time Frame:6 months
Safety Issue:
Description:Evaluation of anti-tumor activity will be performed according to Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST).
Measure: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
Safety Issue:
Description:
Measure:Pharmacodynamic activity of BBI608 administered in combination with the selected immunotherapeutic agent as assessed by biomarker analysis
Time Frame:6 months
Safety Issue:
Description:Histopathology and Cancer Stem Cell assays will be performed to provide information of the biomarkers on biopsied patient tumor tissue, and archival samples.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boston Biomedical, Inc

Trial Keywords

  • Neoplasms

Last Updated

July 11, 2017