Clinical Trial: Vismodegib in Treating Patients With Advanced Chondrosarcomas

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2 Study of GDC-0449 in Patients With Advanced Chondrosarcomas

Brief Summary: This phase II trial studies how well vismodegib works in treating patients with chondrosarcomas that have spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as vismodegib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the antitumor activity of GDC-0449 (vismodegib) in terms of 6-month clinical benefit rate (complete response, partial response, and stable disease, as per the revised Response Evaluation Criteria in Solid Tumors [RECIST] criteria 2009).

SECONDARY OBJECTIVES:

I. Best overall response (as per the revised RECIST criteria 2009). II. 1- and 2-year progression-free survival. III. 1- and 2-year overall survival. IV. GDC-0449 safety. V. Pharmacogenomics analysis of predictive markers of treatment outcome.

OUTLINE:

Patients receive vismodegib orally (PO) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Clinical benefit (complete response [CR] + partial response [PR] + stable disease [SD]) rate per RECIST criteria 2009 [ Time Frame: At 6 months ]

At six months, patients will be classified as success (alive at 6 months AND CR/PR/ SD) or failure (dead OR alive with progression).


Original Primary Outcome: 6-month clinical benefit (CR + PR + SD) rate

Current Secondary Outcome:

  • Duration of response [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years ]
    Will be described in responding subjects using descriptive statistics (median, extreme values, etc.).
  • Expression pattern of hedgehog signaling molecules by using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry [ Time Frame: Baseline ]
    The 6-months clinical benefit rate will be correlated with the expression score of hedgehog signaling molecules in order to identify predictive factors of clinical benefit from GDC-0449.
  • Mutational status of patched 1 (PTCH1) and smoothened SMO [ Time Frame: Baseline ]
    The 6-months clinical benefit rate will be correlated with the mutational status of PTCH and SMO in order to identify predictive factors of clinical benefit from GDC-0449.
  • Overall survival (OS) per RECIST criteria 2009 [ Time Frame: Time from start of treatment to the time of death, assessed up to 3 years ]
    OS will be analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method.
  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years ]
    Will be analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method.


Original Secondary Outcome:

  • Progression-free and overall survival
  • Duration of response
  • Safety of GDC-0449
  • The predictive value of biomarkers


Information By: National Cancer Institute (NCI)

Dates:
Date Received: December 28, 2010
Date Started: December 2010
Date Completion:
Last Updated: March 9, 2017
Last Verified: March 2017