Pemetrexed and Cisplatin in Treating Patients With Advanced, Persistent, or Recurrent Cervical Cancer

Study Overview
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Brief Summary
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RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with cisplatin may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects of giving pemetrexed together with cisplatin and to see how well it works in treating patients with advanced, persistent, or recurrent cervical cancer.

Detailed Description
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OBJECTIVES: Primary To estimate the antitumor activity of pemetrexed disodium and cisplatin with objective tumor response (partial and complete response) in patients with advanced, persistent, or recurrent carcinoma of the cervix. To determine the nature and degree of toxicity of this regimen in these patients. Secondary To determine the effects of this regimen on progression-free survival and overall survival. OUTLINE: This is a multicenter study. Patients are stratified according to prior cisplatin therapy as a radiosensitizer (yes vs no). Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 1-4 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Official Title
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A Limited Access Phase II Trial of Pemetrexed (Alimta, LY231514) (NSC #698037) in Combination With Cisplatin (NSC #119875) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: pemetrexed disodium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous or nonsquamous cell carcinoma of the cervix Advanced, persistent, or recurrent disease Disease not amenable to curative therapy Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Must have ≥ 1 target lesion to be used to assess response Tumors within a previously irradiated field will be designated as non-target lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days following completion of radiotherapy PATIENT CHARACTERISTICS: GOG performance status 0-2 Platelet count ≥ 100,000/mm^3 ANC ≥ 1,500/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) Creatinine clearance ≥ 60 mL/min SGOT ≤ 2.5 times ULN (≤ 5 times ULN if due to hepatic metastases) Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN if due to hepatic metastases) Negative pregnancy test Fertile patients must use effective contraception Neuropathy (sensory and motor) ≤ grade 1 Able to take folic acid, vitamin B12, and dexamethasone according to study protocol No history of other invasive malignancies within the past 5 years, except nonmelanoma skin cancer No active infection requiring antibiotics with the exception of uncomplicated UTI No presence of third space fluid which cannot be controlled by drainage PRIOR CONCURRENT THERAPY: Recovered from effects of recent surgery, radiotherapy, or other therapy At least 1 week since prior hormonal therapy directed at the malignant tumor At least 4 weeks since prior radiotherapy More than 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin and patient remains free of recurrent or metastatic disease No prior radiotherapy to any portion of the abdominal cavity or pelvis except for the treatment of cervical cancer No prior radiotherapy to more than 25% of marrow-bearing areas No prior cancer treatment that contraindicates study treatment No prior cytotoxic drugs for advanced or recurrent carcinoma of the cervix Prior cisplatin as a radiosensitizer for primary treatment of disease allowed No nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates 2-5 days before, during, or for 2 days after receiving pemetrexed disodium No NSAIDS with a long half-life (e.g., naproxen, piroxicam, diflunisal, or nabumetone) 5 days before, during, and for 2 days after receiving pemetrexed disodium Concurrent hormone replacement therapy is permitted Concurrent daily low-dose acetylsalicylic acid therapy (≤ 325 mg/day) allowed Concurrent use of acetylsalicylic acid (up to 1.3 g/day) allowed

Ages Eligible for Study
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Maximum Age: 120 Years

Sexes Eligible for Study
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Female

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 and cisplatin<br>Pemtrexed plus cisplatin on day 1 every 21 days | Drug: cisplatin<br>* Cisplatin as an IV infusion at less than 1 mg/min over less than 4 hours at a dose of<br>Drug: pemetrexed disodium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. | CT scan or MRI if used to follow lesion for measurable disease every other cycle until disease progression or study withdrawal; and at any other time if clinically indicated, up to 5 years. | 
| Frequency and Severity of Observed Adverse Effects | All eligible and evaluable patients | every 21 days during study treatment and up to 30 days after the last cycle of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Duration of progression-free survival in months. | From enrollment onto the study until the onset of disease progression or death, up to 5 years | 
| Duration of Overall Survival | Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. | Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually, up to 5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical squamous cell carcinoma, recurrent cervical cancer, stage III cervical cancer, stage IVA cervical cancer, stage IVB cervical cancer