Vismodegib in Treating Patients With Advanced Chondrosarcomas

NCT01267955 | Active Not Recruiting Phase 2 Results FDA Drug

• 5 other identifiers: NCI-2011-02564CDR0000691728IB-CHONDROGCHONDROG8408
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 6

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.

Conditions

Mesenchymal Chondrosarcoma; Primary Central Chondrosarcoma; Metastatic Chondrosarcoma; Unresectable Primary Central Chondrosarcoma; Clear Cell Chondrosarcoma; Dedifferentiated Chondrosarcoma; Locally Advanced Chondrosarcoma

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR) Based on Centralized Imaging Review as Per RECIST 1.1

  CBR was defined as the percentage of participants with complete or partial responses (CR, PR) or stable disease (SD) per RECIST 1.1. CR was defined as disappearance of all non-nodal target lesions. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Analysis of response was performed based on radiological centralized review. A 2-stage optimal Simon's design with 37 participants (first stage: 17 participants) was used. If 3 or less non-progressions (CR + PR + SD) at 6 months were observed during stage 1 (out of 17 participants), the trial would stopped early. Otherwise, 20 additional patients would be accrued for stage 2. If 11 or more non-progressions (out of 37 participants) were observed at the end of recruitment, further investigation of this therapy would be warranted.

  At 6 months after inclusion

Secondary Outcomes (5)

• Progression-free Survival

  Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years

• Overall Survival Per Response Evaluation Criteria in Solid Tumors Criteria 2009

  Time from start of treatment to the time of death, assessed up to 3 years

• Duration of Response

  From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years

• Mutational Status of Patched 1 and Smoothened

  Baseline

• Expression Pattern of Hedgehog Signaling Molecules by Using Quantitative Reverse Transcription-polymerase Chain Reaction and Immunohistochemistry

  Baseline

Study Arms (1)

Treatment (vismodegib)

EXPERIMENTAL

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

Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study; Drug: Vismodegib

Interventions

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC 0449, GDC-0449, GDC0449, Hedgehog Antagonist GDC-0449

Treatment (vismodegib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (vismodegib)

Pharmacogenomic Study OTHER

Correlative studies

Also known as: PHARMACOGENOMIC

Treatment (vismodegib)

Eligibility Criteria

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

You may qualify if:

• 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 24 months post-treatment for female patients and for 2 months for male patients; 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 7 days prior to initiation 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

You may not qualify if:

• 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 ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

Institut Bergonie Cancer Center

Bordeaux, 33076, France

Location

Centre Oscar Lambert

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital De La Timone

Marseille, 13385, France

Location

Institut Curie Paris

Paris, 75005, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (1)

• Italiano A, Le Cesne A, Bellera C, Piperno-Neumann S, Duffaud F, Penel N, Cassier P, Domont J, Takebe N, Kind M, Coindre JM, Blay JY, Bui B. GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/US and French National Cancer Institute Single-Arm Phase II Collaborative Study. Ann Oncol. 2013 Nov;24(11):2922-6. doi: 10.1093/annonc/mdt391.

  PMID: 24170610 DERIVED

MeSH Terms

Conditions

Chondrosarcoma, Clear Cell; Chondrosarcoma, Mesenchymal; Chondrosarcoma

Interventions

Pharmacogenomic Testing; HhAntag691

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Results Point of Contact

• Title: Pr Italiano Antoine, Department of Medical Oncology
• Organization: Institut Bergonie

a.italiano@bordeaux.unicancer.fr

0524071947

Study Officials

• Antoine Italiano

  Institut Bergonie Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2010
• First Posted: December 29, 2010
• Study Start: December 21, 2010
• Primary Completion: June 30, 2018
• Study Completion (Estimated): July 21, 2026
• Last Updated: April 13, 2026
• Results First Posted: November 15, 2019

Record last verified: 2026-01

Locations

FR (6)