A Study of BBI608 in Adult Patients With Advanced Malignancies

Inclusion criteria

• Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (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
• For solid tumors or lymphoma, 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
• For solid tumors, measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
• For lymphoma, measurable disease as defined by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma
• For multiple myeloma, measurable disease as defined by the International Uniform Response Criteria for Multiple Myeloma
• Karnofsky performance status greater than or equal to 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) less than or equal to 1.5 × upper limit of normal(ULN)
• Hemoglobin (Hgb) greater than or equal to 10 g/dl
• Total bilirubin less than or equal to 1.5 × ULN
• Creatinine less than or equal to 1.5 x ULN or creatinine clearance greater than 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. Creatinine < 2.5 x ULN for multiple myeloma patients.
• Absolute neutrophil count greater than or equal to 1.5 x 109/L
• Platelets greater than or equal to 100 x 109/L
• Life expectancy greater than or equal to 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 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 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