Pemetrexed Disodium in Treating Patients With Recurrent Cancer of the Cervix

A Phase II Evaluation Of Pemetrexed (ALIMTA, LY231517, IND #40061) In the Treatment Of Recurrent Carcinoma Of The Cervix

RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well pemetrexed disodium works in treating patients with recurrent cancer of the cervix.

OBJECTIVES:

• Determine the antitumor activity of pemetrexed disodium in patients with recurrent carcinoma of the cervix that failed higher priority treatment protocols.
• Determine the nature and degree of toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

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 and continuing until 3 weeks after the last dose of pemetrexed disodium, patients also receive oral folic acid daily and cyanocobalamin (vitamin B_12) intramuscularly every 9 weeks.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: Approximately 22-60 patients will be accrued for this study within 1-2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma of the cervix

  • Squamous cell or non-squamous cell
  • Recurrent disease
  • Progressive disease

• Measurable disease

  • At least 1 unidimensionally measurable target lesion ≥ 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, or MRI OR ≥ 10 mm by spiral CT scan
  • Tumors within a previously irradiated field are considered non-target lesions unless disease progression is documented or a biopsy is obtained to confirm persistence at least 90 days after completion of radiotherapy

• Not amenable to surgery, radiotherapy, or other therapy

• Must have received 1 prior systemic chemotherapy regimen for persistent or recurrent squamous cell or non-squamous cell carcinoma of the cervix

  • Chemotherapy administered with primary radiotherapy as a radiosensitizer is not considered a systemic chemotherapy regimen

• Not eligible for a higher priority GOG protocol (i.e., any active phase III GOG protocol for the same patient population)

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• AST and ALT ≤ 3 times upper limit of normal (ULN)*
• Alkaline phosphatase ≤ 3 times ULN*
• Bilirubin ≤ 1.5 times ULN NOTE: * ≤ 5 times ULN if liver metastases are present

Renal

• Creatinine clearance ≥ 45 mL/min

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study participation
• Neuropathy (sensory and motor) ≤ grade 1
• No active infection requiring antibiotics
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 weeks since prior biologic or immunologic agents for the malignant tumor

• At least 24 hours since prior growth factors

• One prior non-cytotoxic (biologic or cytostatic) regimen for recurrent or persistent disease allowed, including, but not limited to, the following:

  • Monoclonal antibodies
  • Cytokines
  • Small-molecule inhibitors of signal transduction

• No concurrent routine colony-stimulating factors

Chemotherapy

• See Disease Characteristics
• Recovered from prior chemotherapy
• No more than 1 prior cytotoxic chemotherapy regimen with either single or combination cytotoxic drug therapy
• No prior pemetrexed disodium

Endocrine therapy

• At least 1 week since prior hormonal therapy for the malignant tumor
• Concurrent hormone replacement therapy allowed

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy and recovered
• No prior radiotherapy to > 25% of bone marrow

Surgery

• Recovered from prior surgery

Other

• At least 3 weeks since other prior therapy for the malignant tumor

• No nonsteroidal anti-inflammatory drugs for 2-5 days before, during, and for 1-2 days after study drug administration

  • Concurrent daily low-dose (≤ 325 mg/day) aspirin therapy allowed

• No prior therapy that would contraindicate study participation