Vismodegib 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: March 19, 2014
Last verified: March 2014
  Purpose

This phase II trial is studying how well vismodegib works in treating patients with advanced chondrosarcomas. Drugs used in chemotherapy, such as vismodegib, 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:


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

Primary Outcome Measures:
  • Clinical benefit (CR + PR + SD) rate [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    At six months, patients will be classified as success (alive at 6 months AND CR/PR/ SD) or failure (dead OR alive with progression).


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 3 years ] [ 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 years ] [ 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 years ] [ Designated as safety issue: No ]
    Will be described in responding subjects using descriptive statistics (median, extreme values, etc.).


Estimated Enrollment: 45
Study Start Date: December 2010
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vismodegib)
Patients receive vismodegib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicities.
Drug: vismodegib
Given PO
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 (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. 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 pharmacogenomics analysis of predictive markers of treatment outcome.

OUTLINE: This is a multicenter study.

Patients receive vismodegib orally (PO) 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)
  • 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 >= 10 mm with spiral computed tomography (CT) scan
  • No more than three prior lines of chemotherapy for advanced disease (including no more than 450 mg/m^2 doxorubicin); at least three weeks since last chemotherapy (six weeks in case of nitrosoureas and mitomycin C), immunotherapy or any other pharmacological treatment and/or radiotherapy
  • Life expectancy of greater than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Metastatic or unresectable locally advanced disease
  • Documented disease progression (as per RECIST) before study entry
  • 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; women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior to the first dose of GDC-0449 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks while on study within the 24-hour period prior to the administration of GDC-0449; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449
  • Ability to understand and the willingness to sign a written informed consent document
  • In accordance with French Regulatory Authorities: Patients with French Social Security in compliance with the French law relating to biomedical research (Huriet Law 88-1138 and related decrees)

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study
  • Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be 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
  • Tumor tissue sample not available for pathological review and/or correlative studies
  • 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
  • Pregnant women are excluded from this study because GDC-0449 is a Hh pathway inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GDC-0449, breastfeeding should be discontinued if the mother is treated with GDC-0449; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01267955

Locations
France
Institut Bergonie Cancer Center
Bordeaux, France, 33000
Centre Oscar Lambert
Lille, France, 59020
Centre Leon Berard
Lyon, France, 69373
Hopital De La Timone
Marseille, France, 13005
Institut Curie Paris
Paris, France, 75005
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
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, NCI-2011-02564, CDR0000691728, IB-CHONDROG, 8408, 8408
Study First Received: December 28, 2010
Last Updated: March 19, 2014
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 April 17, 2014