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

Tracking Information
First Submitted Date ICMJE	June 4, 2015
First Posted Date ICMJE	June 10, 2015
Last Update Posted Date	April 3, 2018
Study Start Date ICMJE	August 2015
Estimated Primary Completion Date	December 2018 (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	Complete list of historical versions of study NCT02467361 on ClinicalTrials.gov Archive Site
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 Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	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	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	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	Active, not recruiting
Estimated Enrollment ICMJE; (submitted: June 5, 2015)	120
Original Estimated Enrollment ICMJE	Same as current
Study Completion Date	Not Provided
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion criteria: Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements; 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.; ≥ 18 years of age; Measurable disease as defined by Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST).; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 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; Females of childbearing potential must have a negative serum pregnancy test; Aspartate transaminase (AST) < 2.5 x upper limit of normal (ULN) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN).; Hemoglobin (Hgb) ≥ 9 g/dl; 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.; 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.; Absolute neutrophil count ≥ 1.5 x 10^9/L; Platelets ≥ 100 x 10^9/L; patients with hepatocellular carcinoma may enroll provided they have a platelet count ≥ 75 x 10^9/L.; Life expectancy ≥ 3 months Exclusion criteria: 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; Had a surgical procedure requiring general anesthesia or inpatient hospitalization for recovery less than 4 weeks prior to beginning protocol therapy.; 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.; Pregnant or breastfeeding; Unable or unwilling to swallow BBI608 capsules daily; 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.; 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.; Has interstitial lung disease or active, non-infectious pneumonitis; Has a transplanted organ or has undergone allogeneic bone marrow transplant; Has received a live vaccine within 30 days prior to first dose.; Known hypersensitivity to a component of protocol therapy; 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; 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.; 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	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	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	Not Provided
Responsible Party	Boston Biomedical, Inc
Study Sponsor ICMJE	Boston Biomedical, Inc
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Boston Biomedical, Inc
Verification Date	March 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP