Vismodegib in Treating Patients With Advanced Chondrosarcomas
Condition: Clear Cell Chondrosarcoma; Dedifferentiated Chondrosarcoma; Locally Advanced Chondrosarcoma; Mesenchymal Chondrosarcoma; Metastatic Chondrosarcoma; Primary Central Chondrosarcoma; Unresectable Primary Central Chondrosarcoma
MeSH terms: Chondrosarcoma; Chondrosarcoma, Mesenchymal; Chondrosarcoma, Clear Cell
Intervention: Laboratory Biomarker Analysis; Pharmacogenomic Study; Vismodegib
Intervention description: Correlative studies; Correlative studies; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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 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

               -  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 > 50 years old

                    -  The patient has permanent premature ovarian failure confirmed by specialist
                       gynecologist

          -  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 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