S0423 Pemetrexed Disodium in Treating Patients With Recurrent and Unresectable or Metastatic Chondrosarcoma

Study Overview
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Brief Summary
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RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well pemetrexed disodium works in treating patients with recurrent and unresectable or metastatic chondrosarcoma.

Detailed Description
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OBJECTIVES: Primary Determine the response rate (confirmed and unconfirmed complete response and partial response) in patients with recurrent and unresectable or metastatic chondrosarcoma treated with pemetrexed disodium. Secondary Determine the toxicity of this drug in these patients. Correlate, preliminarily, response rates with deletions of methylthioadenosine phosphorylase (MTAP), as analyzed by fluorescence in-situ hybridization (FISH), in patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (yes vs no). Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days* in the absence of disease progression or unacceptable toxicity. Beginning 7 days before the first dose of pemetrexed disodium and continuing until 21 days after the completion of pemetrexed disodium, patients receive cyanocobalamin (vitamin B_12) intramuscularly once every 63 days and oral folic acid once daily. NOTE: *The duration of course 1 is 28 days; the duration of all subsequent courses is 21 days. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients achieving a confirmed partial response (PR) that is resectable, proceed to surgical resection and then receive 2 additional courses of therapy after recovering from surgery. Patients achieving a confirmed PR that is not resectable continue treatment in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 5 years. PROJECTED ACCRUAL: A total of 40-75 patients (20-40 in the previously treated stratum and 20-35 in the previously untreated stratum) will be accrued for this study within 20-37.5 months.

Official Title
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Phase II Trial of Pemetrexed for Advanced Chondrosarcomas

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: pemetrexed disodium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed chondrosarcoma Histologic grade G2 or G3 Recurrent and unresectable OR metastatic disease Measurable disease by x-ray, scan, ultrasound, or physical examination No known CNS metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin < 1.5 times upper limit of normal (ULN) SGOT or SGPT < 2.5 times ULN (5 times ULN if liver metastases are present) Renal Creatinine clearance > 45 mL/min Other Not pregnant or nursing Fertile patients must use effective contraception Able to swallow oral medication No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy More than 28 days since prior biologic therapy for this malignancy Chemotherapy More than 28 days since prior chemotherapy for this malignancy Endocrine therapy Not specified Radiotherapy At least 60 days since prior radiotherapy to the target lesion* No concurrent radiotherapy NOTE: *Target lesion must have demonstrated disease progression after completion of therapy Surgery At least 21 days since prior surgery and recovered Other More than 28 days since prior investigational drugs for this malignancy At least 60 days since prior embolization or radiofrequency ablation to the target lesion* No more than 2 prior treatment regimens for this malignancy No concurrent antiretroviral therapy for HIV-positive patients NOTE: *Target lesion must have demonstrated disease progression after completion of therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pemetrexed<br>pemetrexed | Drug: pemetrexed disodium<br>* pemetrexed, 500 mg/m2, IV, every 21 days until two cycles after complete response or until progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate as measured by RECIST criteria | x-rays or scans | every 9 weeks during treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as measured by CTC v 3.0 | side-effect evaluation | every 3 weeks during treatment | 
| Response rate compared with methylthioadenosine phosphorylase (MTAP) deletions as measured by fluorescence in-situ hybridization (FISH) retrospectively |  | end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chondrosarcoma