A Study of BBI503 in Adult Patients With Advanced Urologic Malignancies

Sumitomo Pharma

Status and phase

Withdrawn

Phase 2

Conditions

Urothelial Carcinoma

Renal Cell Carcinoma

Urologic Malignancies

Treatments

Drug: BBI503

Study type

Interventional

Funder types

Industry

Identifiers

NCT02232646

BBI503-205a

Details and patient eligibility

About

This is an open label, multi-center, Phase II study of BBI503 administered to adult patients with selected advanced urologic malignancies. The primary objective of this study is to evaluate the disease control rate of patients with renal cell cancer and urothelial carcinoma treated with BBI503.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed written informed consent
Histologically or cytologically confirmed renal cell cancer or urothelial carcinoma that is metastatic, unresectable, or recurrent.
≥ 18 years of age
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
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 BBI503 dose
Females of childbearing potential must have a negative serum pregnancy test
Alanine transaminase (ALT) ≤ 2.5 x the upper limit of normal (ULN), or ≤ 3.5 x ULN in the presence of primary or metastatic hepatic lesions
Hemoglobin (Hgb) ≥ 10 g/dl
Total bilirubin ≤ 1.5 x ULN
Creatinine ≤ 1.5 x ULN or creatinine clearance > 50 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
Prothrombin time (PT) ≤ 16 seconds and partial thromboplastin time (PTT) ≤ 1.5 x ULN
Life expectancy ≥ 3 months
A patient with renal cell carcinoma (RCC) must be classified into clear-cell or non-clear cell subtype, and must then meet the following criteria:
- Patients with clear cell renal cancer must have received prior treatment with at least one line of standard systemic therapy which included treatment with a tyrosine kinase inhibitor; either alone or in combination. The patient must have had either progressive disease during treatment, or have had documented intolerance to first line tyrosine kinase inhibitor (TKI)-based therapy.
- Patients with clear cell renal cancer who have received anti-cancer treatment beyond first-line TKI-based therapy may enroll.
- Patients with clear cell renal cancer who have not received anti-cancer treatment beyond first-line TKI-based therapy may enroll only after discussing the potential risks and benefits of alternative treatment options, such as other currently available agents approved for treatment of patients with clear cell renal cancer.
- Patients with non-clear cell RCC which is metastatic may enroll without having received prior treatment in the metastatic setting
A patient with urothelial carcinoma must also meet the following criteria:
- Must have received at least one prior line of standard systemic cytotoxic therapy in the metastatic setting.

Exclusion criteria

Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 7 days of first dose of BBI503. Patients may begin BBI503 on a date determined by the investigator and medical monitor for the sponsor provided there is a minimum of 7 days since last receiving anti-cancer treatment, and that all prior treatment-related adverse events (AEs) have resolved or have been deemed irreversible.
Major surgery within 4 weeks prior to first dose (requiring general anesthesia and/or inpatient hospitalization for recovery).
Any known symptomatic or untreated brain metastases requiring increase of steroid dose within 2 weeks prior to starting on study. Patients with treated brain metastases must be stable for 4 weeks after completion of that treatment. Post-treatment image documentation of stability is required within 4 months of starting on study. 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 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 (e.g. no reliable transportation).
Patients with a history of malignancies other than the tumor of interest except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for > 3 years.
Abnormal ECGs which are clinically significant such as QT prolongation - QTc > 480 msec, clinically significant cardiac enlargement or hypertrophy, new bundle branch block, or signs of active ischemia. Patients with evidence of prior infarction who are New York Heart Association (NYHA) functional class II, III, or IV are excluded, as are patients with marked arrhythmia such as Wolff Parkinson White pattern or complete atrioventricular (AV) dissociation.