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

• ClinicalTrials.gov Identifier: NCT00691301
• Recruitment Status: Completed
• First Posted: June 5, 2008
• Results First Posted: January 9, 2018
• Last Update Posted: January 9, 2018
• Sponsor: Gynecologic Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): GOG Foundation ( Gynecologic Oncology Group )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cervical Cancer	Drug: cisplatin; Drug: pemetrexed disodium	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: September 2008
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: July 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pemetrexed and cisplatin; Pemtrexed plus cisplatin on day 1 every 21 days	Drug: cisplatin; Cisplatin as an IV infusion at less than 1 mg/min over less than 4 hours at a dose of; Drug: pemetrexed disodium

Outcome Measures

Primary Outcome Measures :

1. Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 [ Time Frame: 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. ]
   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.
2. Frequency and Severity of Observed Adverse Effects [ Time Frame: every 21 days during study treatment and up to 30 days after the last cycle of treatment. ]
   All eligible and evaluable patients

Secondary Outcome Measures :

1. Progression-free Survival [ Time Frame: From enrollment onto the study until the onset of disease progression or death, up to 5 years ]
   Duration of progression-free survival in months.
2. Duration of Overall Survival [ Time Frame: 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. ]
   Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

Eligibility Criteria

• Ages Eligible for Study: up to 120 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States, 90089-9181

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

Orange, California, United States, 92868

United States, Mississippi

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States, 39216

United States, Nevada

Women's Cancer Center - La Canada

Las Vegas, Nevada, United States, 89169

United States, Ohio

MetroHealth Cancer Care Center at MetroHealth Medical Center

Cleveland, Ohio, United States, 44109

United States, Oklahoma

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States, 73104

Cancer Care Associates - Saint Francis Campus

Tulsa, Oklahoma, United States, 74136-1929

United States, Texas

Parkland Memorial Hospital

Dallas, Texas, United States, 75235

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States, 75390

Lyndon B. Johnson General Hospital

Houston, Texas, United States, 77026-1967

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States, 77030-4009

United States, Virginia

Carilion Gynecologic Oncology Associates

Roanoke, Virginia, United States, 24016

Sponsors and Collaborators

Gynecologic Oncology Group

National Cancer Institute (NCI)

Investigators

• Study Chair: David S. Miller, MD; Simmons Cancer Center

More Information

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00691301
• Other Study ID Numbers: GOG-0076GG; GOG-0076GG; CDR0000597154 ( Other Identifier: CDR ); NCI-2009-00572 ( Other Identifier: NCI )
• First Posted: June 5, 2008
• Results First Posted: January 9, 2018
• Last Update Posted: January 9, 2018
• Last Verified: May 2015

Keywords provided by GOG Foundation ( Gynecologic Oncology Group ):

cervical squamous cell carcinoma; recurrent cervical cancer; stage III cervical cancer; stage IVA cervical cancer; stage IVB cervical cancer

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Cisplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors