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.

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.

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