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

A Limited Access Phase II Trial of Cetuximab (C225, NSC #714692) in Combination With Cisplatin (NSC #119875) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also help cisplatin work better by making tumor cells more sensitive to the drug. 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 cetuximab together with cisplatin may be a better way to block tumor growth.

PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin works in treating patients with advanced, persistent, or recurrent cervical cancer.

OBJECTIVES:

Primary

• Determine the antitumor activity of cetuximab and cisplatin, in terms of objective tumor response (partial and complete), in patients with advanced, persistent, or recurrent carcinoma of the cervix.
• Determine the nature and degree of toxicity of this regimen in these patients.

Secondary

• Determine the progression-free survival and overall survival of patients treated with this regimen.
• Correlate epidermal growth factor receptor expression with progression-free survival, overall survival, and response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and cisplatin IV on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.

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

PROJECTED ACCRUAL: A total of 28-62 patients will be accrued for this study within 9-20 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous or non-squamous cell carcinoma of the cervix

  • Advanced, persistent, or recurrent disease
  • Documented disease progression

• Not amenable to curative therapy

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• At least 1 target lesion

  • Tumors within a previously irradiated field are designated as non-target lesions unless progression is documented or a biopsy is obtained ≥ 90 days after completion of radiotherapy to confirm persistence

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Platelet count ≥ 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No significant history of cardiac disease within the past 6 months, including the following:

  • Unstable angina
  • Uncontrolled hypertension
  • Uncontrolled congestive heart failure
  • Uncontrolled arrhythmia

Neurologic

• No uncontrolled seizure disorder
• No active neurological disease
• No neuropathy (sensory and motor) > grade 1

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring antibiotics
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior anti-epidermal growth factor receptor (EGFR) antibody therapy
• No prior chimerized or murine monoclonal antibody therapy

Chemotherapy

• Not specified

Endocrine therapy

• At least 1 week since prior anticancer hormonal therapy
• Concurrent hormone replacement therapy allowed

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery

• More than 30 days since prior major surgery, except diagnostic biopsy

Other

• Recovered from all prior therapy
• No prior cytotoxic therapy for cervical cancer
• No prior tyrosine kinase inhibitor therapy that targets the EGFR pathway
• No prior cancer treatment that would contraindicate study therapy
• No other concurrent investigational agents