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GDC-0449 in Treating Patients With Advanced Chondrosarcomas

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01267955
First received: December 28, 2010
Last updated: December 21, 2012
Last verified: December 2012
History of Changes
  Purpose

This phase II trial is studying how well GDC-0449 works in treating patients with advanced chondrosarcomas. Drugs used in chemotherapy, such as GDC-0449, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing


Condition Intervention Phase
Chondrosarcoma
 Drug: vismodegib
Other: diagnostic laboratory biomarker analysis
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of GDC-0449 in Patients With Advanced Chondrosarcomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer
Drug Information available for: Vismodegib
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 6-month clinical benefit (CR + PR + SD) rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    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.

  • Overall survival [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    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.

  • Duration of response [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Will be described in responding subjects using descriptive statistics (median, extreme values, etc.).


Estimated Enrollment: 41
Study Start Date: December 2010
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral Hedgehog antagonist GDC-0449 on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicities.
 Drug: vismodegib
Given orally
Other Names:
  • Erivedge
  • GDC-0449
  • Hedgehog antagonist GDC-0449
Other: diagnostic laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Evaluate the antitumor activity of GDC-0449 in terms of 6-month clinical benefit rate (complete response, partial response, and stable disease, as per the revised RECIST criteria 2009).

SECONDARY OBJECTIVES:

I. Determine the best overall response (as per the revised RECIST criteria 2009).

II. Determine the 1- and 2-year progression-free survival. III. Determine the 1- and 2-year overall survival. IV. Assess GDC-0449 safety. V. Conduct a pharmacogenomic analysis of predictive markers of treatment outcome.

OUTLINE: This is a multicenter study.

Patients receive oral Hedgehog antagonist GDC-0449 on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicities.

Tumor samples are analyzed for correlative, including biomarker, studies.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed diagnosis of chondrosarcoma (conventional, mesenchymal, dedifferentiated or clear cell subtypes)

    • Metastatic or unresectable locally advanced disease
    • Documented disease progression (as per RECIST) before study entry
  • Patients must have measurable disease (outside any previously irradiated field) defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan
  • No more than three prior lines of chemotherapy for advanced disease (including no more than 450 mg/m² doxorubicin)
  • Tumor tissue sample available for pathological review and/or correlative studies
  • No known brain metastases
  • ECOG performance status < 2 (Karnofsky > 60%)
  • Life expectancy of greater than 3 months
  • Leukocytes > 3,000/mcL
  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST/ALT < 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min
  • Not pregnant or nursing
  • Negative serum pregnancy test
  • Women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 12 months post-treatment
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study
  • No malabsorption syndrome or other condition that would interfere with intestinal absorption
  • Able to swallow capsules
  • Patients with clinically important history of liver disease, including viral or other hepatitis, or cirrhosis are ineligible
  • Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation, are excluded from this study

  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • HIV-positive patients on combination antiretroviral therapy are ineligible
  • No other investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy
  • At least three weeks since last chemotherapy (six weeks in case of nitrosoureas and mitomycin C), immunotherapy, radiotherapy, and/or any other pharmacological treatment and recovered
  • Patients may not be receiving any other investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01267955

Locations
France
Institut Bergonie Cancer Center
Bordeaux, France, 33000
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Antoine Italiano Institut Bergonie Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01267955     History of Changes
Other Study ID Numbers: NCI-2011-02564, IB-CHONDROG, CDR0000691728
Study First Received: December 28, 2010
Last Updated: December 21, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Chondrosarcoma
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
 Neoplasms by Histologic Type
Neoplasms
Sarcoma

ClinicalTrials.gov processed this record on May 23, 2013