A Study of Vismodegib in Men With Metastatic CRPC With Accessible Metastatic Lesions for Tumor Biopsy

• Status: Completed
• Trial end date: 2016-04-01
• Target enrollment: 0
• Participant gender: Male

Summary

This is a single-arm pharmacodynamic study with mandatory metastatic tumor biopsies in men with castration-resistant prostate cancer.

The trial will evaluate the effect of vismodegib on tumor tissue in men with metastatic CRPC by obtaining tumor biopsies at baseline and after 4 weeks of treatment with vismodegib.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Criteria

Inclusion Criteria:

• Men with metastatic castration-resistant prostate cancer (mCRPC), with accessible metastatic soft-tissue lesions for tumor biopsy

• Greater than 18 years of age

• Evidence of disease progression (PSA progression, or radiographic/clinical progression [PCWG2])

• PSA progression is defined as at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value ≥ 2.0 ng/mL.

• Radiographic progression is defined for soft tissue lesions using RECIST criteria, i.e. an increase greater than 20% in the sum of the longest diameter of all target lesions based on the smallest sum longest diameter since treatment started or the appearance of one of more new lesions with a confirmatory scan 6 or more weeks later. Radiographic progression will be defined for bone lesions as the appearance of two new lesions with a confirmatory scan performed 6 or more weeks later that shows at least 2 or more additional new lesions.

• Presence of ≥1 metastatic site (nodal, visceral) that is amenable to core biopsy

• Castrate serum testosterone (<50 ng/dL)

• Prior anti-androgens are permitted but not required (2 week washout from anti-androgens)

• Prior abiraterone and enzalutamide are permitted (2 week washout for both agents)

• Prior immunotherapy (e.g. sipuleucel-T), and chemotherapy are permitted (4 week washout period from chemotherapy)

• Bisphosphonates and denosumab are permitted, if on a stable dose for ≥4 weeks

• Life expectancy ≥12 months

• Adequate renal, liver, and bone marrow function with the following acceptable initial laboratory values:

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be ≤ 2.5 x the upper limit of normal (ULN).

• Total bilirubin must be ≤ 1.5 x ULN.

• Estimated creatinine clearance using the Cockcroft-Gault formula must be > 40 mL/minute (See section 12.2 for formula)

• Absolute neutrophil count (ANC) must be ≥ 1500/μL

• Platelet count must be ≥ 100,000/μL

• Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.

NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.

• Karnofsky Performance status/ECOG Performance Status ≥70/2 (Appendix A: Performance Status Criteria)

• Male patients must use condoms at all times, even after a vasectomy, during sexual intercourse with female partners of reproductive potential during treatment with vismodegib and for 2 months after the last dose to avoid exposing a pregnant partner and unborn fetus to vismodegib.

Exclusion Criteria:

• Current use of systemic corticosteroids (>5 mg prednisone)

• Known brain metastases, or untreated meningeal/dural disease

• Receiving any other investigational agents or receipt of another investigational agent within 4 weeks of study entry

• Patients taking anticoagulants or with a history of a bleeding diathesis (due to need for visceral biopsy)

• Use of any prohibited concomitant medications (washout period of 1 week)

• Insufficient time from last prior regimen or radiation exposure (washout period of 4 weeks)

• Grade > 2 treatment-related toxicity from prior therapy

• Any other condition which, in the opinion of the Investigator, would preclude participation in this trial