Clinical trial NCT00691301: Pemetrexed and Cisplatin in Treating Patients With Advanced, Persistent, or Recurrent Cervical Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Keywords: cervical squamous cell carcinoma
recurrent cervical cancer
stage III cervical cancer
stage IVA cervical cancer
stage IVB cervical cancer
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-06-05
Enrollment: 55
Sex: FEMALE
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
timeFrame: 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.
measure: Frequency and Severity of Observed Adverse Effects
timeFrame: every 21 days during study treatment and up to 30 days after the last cycle of treatment.
Secondary outcomes:
measure: Progression-free Survival
timeFrame: From enrollment onto the study until the onset of disease progression or death, up to 5 years
measure: Duration of Overall Survival
timeFrame: 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.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
state: California
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Las Vegas
country: United States
facility: Women's Cancer Center - La Canada
state: Nevada
city: Cleveland
country: United States
facility: MetroHealth Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Associates - Saint Francis Campus
state: Oklahoma
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Houston
country: United States
facility: Lyndon B. Johnson General Hospital
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Roanoke
country: United States
facility: Carilion Gynecologic Oncology Associates
state: Virginia
Study officials:
affiliation: Simmons Cancer Center
name: David S. Miller, MD
role: STUDY_CHAIR
References: