A Study of BBI503 in Adult Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open label, single arm dose escalation study of BBI503 in adult patients with advanced solid tumors.

Official Title
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A Phase I Clinical Study of BBI503 in Adult Patients With Advanced Solid Tumors

Conditions
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Cancer, Advanced Solid Tumors

Intervention / Treatment
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* Drug: BBI503


Participation Criteria
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Eligibility Criteria
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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 solid tumor that is metastatic, unresectable, or recurrent and for which standard curative or palliative therapies do not exist or are no longer effective. ≥ 18 years of age Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 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 BBI503 dose Females of childbearing potential must have a negative serum pregnancy test Aspartate transaminase (AST) and alanine transaminase (ALT) < or equal to 1.5 × upper limit of normal (ULN) Hemoglobin (Hgb) ≥ 10 g/dl Total bilirubin < or equal to 1.5 × ULN Creatinine < or equal to 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Absolute neutrophil count < or equal to 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 BBI503 Surgery within 4 weeks prior to first dose Any known untreated brain metastases. Treated subjects 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 resection and small intestinal resection) Unable or unwilling to swallow BBI503 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BBI503<br> | Drug: BBI503<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events as a Measure of Safety and Tolerability | Assessment of safety of BBI503 by reporting of adverse events and serious adverse events. | Adverse events will be assessed at baseline, while the participant is taking BBI503, and for 30 days after stopping therapy. The average length of this duration is expected to be approximately 4 months. | 
| Determination of the recommended Phase 2 dose |  | Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile (Area under the curve) of BBI503 | Blood sampling to assess the pharmacokinetic profile (Area under the curve) of BBI503. | During the first 28 days of treatment | 
| Pharmacodynamic activity | Tumor Biopsy(s) to provide information on analysis of the targets and downstream genes/ effect of BBI503 on cancer stem cells through immunohistochemistry. | During the first 28 days of treatment | 
| Anti-tumor activity | To assess the preliminary anti-tumor activity of BBI503. | Participants will be assessed every eight weeks for anti-tumor activity. |