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: June 30, 2014
Last verified: May 2014

December 28, 2010
June 30, 2014
December 2010
February 2015   (final data collection date for primary outcome measure)
Clinical benefit (CR + PR + SD) rate per RECIST criteria 2009 [ 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).
6-month clinical benefit (CR + PR + SD) rate [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01267955 on ClinicalTrials.gov Archive Site
  • Progression-free survival (PFS) [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed 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 (OS) per RECIST criteria 2009 [ Time Frame: Time from start of treatment to the time of death, assessed up to 3 years ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    Will be described in responding subjects using descriptive statistics (median, extreme values, etc.).
  • Mutational status of patched 1 (PTCH1) and smoothened SMO [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.
  • Expression pattern of hedgehog signaling molecules by using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry (IHC) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.
  • Progression-free and overall survival [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Safety of GDC-0449 [ Designated as safety issue: Yes ]
  • The predictive value of biomarkers [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Vismodegib in Treating Patients With Advanced Chondrosarcomas
A Phase 2 Study of GDC-0449 in Patients With Advanced Chondrosarcomas

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.

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:

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

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

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Chondrosarcoma
  • Drug: vismodegib
    Given PO
    Other Names:
    • Erivedge
    • GDC-0449
    • Hedgehog antagonist GDC-0449
  • Other: laboratory biomarker analysis
    Correlative studies
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.
Interventions:
  • Drug: vismodegib
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
45
Not Provided
February 2015   (final data collection date for primary outcome measure)

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 glutamate 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; 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

    • Women of childbearing potential are defined as follows:

      • Patients with regular menses
      • Patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding
      • Women who have had a tubal ligation
    • Women are considered not to be of childbearing potential for the following reasons:

      • The patient has undergone hysterectomy and/or bilateral oophorectomy
      • The patient is post-menopausal defined by amenorrhea for at least 1 year in a woman > 45 years old
  • 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
  • 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; 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT01267955
NCI-2011-02564, NCI-2011-02564, CDR0000691728, IB-CHONDROG, 8408, 8408
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Antoine Italiano Institut Bergonie Cancer Center
National Cancer Institute (NCI)
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP