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

NCT02115828 | Completed Early Phase 1 Results DMC

• 2 other identifiers: J1423NA_00093427
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostate Cancer

Keywords

Vismodegib; Metastatic Castration-Resistant Prostate Cancer; Accessible Metastatic Lesions for Tumor Biopsy

Outcome Measures

Primary Outcomes (1)

• The Proportion of mCRPC Patients Treated With Vismodegib Who Achieve a Pharmacodynamic (PD) Response in Tumor Biopsies

  The primary endpoint is the proportion of mCRPC patients treated with vismodegib who achieve a pharmacodynamic (PD) response in tumor biopsies, defined as both a decrease in GLI1 mRNA greater than 1.2 times the standard deviation (SD) of the baseline values and a ≥50% (≥2-fold) reduction in GLI1 messenger ribonucleic acid (mRNA) expression in metastatic tumor biopsies after 4 weeks of treatment when comparing post-treatment biopsy to pre-treatment biopsy in the same patient.

  Up to 1 year

Secondary Outcomes (4)

• GLI1 Expression

  Up to 1 Year

• Progression-free Survival (PFS)

  Up to 1 Year

• AKT1 Expression in Tumor Biopsies

  Up to 1 Year

• The Effect of Vismodegib on PSA Responses

  Up to 1 Year

Study Arms (1)

Vismodegib

EXPERIMENTAL

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Drug: Vismodegib

Interventions

Vismodegib DRUG

Vismodegib

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• Maughan BL, Suzman DL, Luber B, Wang H, Glavaris S, Hughes R, Sullivan R, Harb R, Boudadi K, Paller C, Eisenberger M, Demarzo A, Ross A, Antonarakis ES. Pharmacodynamic study of the oral hedgehog pathway inhibitor, vismodegib, in patients with metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2016 Dec;78(6):1297-1304. doi: 10.1007/s00280-016-3191-7. Epub 2016 Nov 8.

  PMID: 27826729 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

HhAntag691

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Emmanuel Antonarakis, MD
• Organization: Johns Hopkins University

eantona1@jhmi.edu

410-502-7528

Study Officials

• Emmanuel Antonarakis, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 16, 2014
• Study Start: April 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 20, 2018
• Results First Posted: July 20, 2018

Record last verified: 2017-10

Locations

US (1)