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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: cisplatin; Biological: cetuximab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
  • Georgia
    • Savannah, Georgia, United States, 31403-3089
      • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Melvin and Bren Simon Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Cancer Institute at Ochsner Clinic Foundation
    • Shreveport, Louisiana, United States, 71101
      • Christus Schumpert Cancer Treatment Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Cancer Clinic
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Fox Chase Virtua Health Cancer Program at Virtua West Jersey
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Cancer Care Center at MetroHealth Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
    • Tulsa, Oklahoma, United States, 74104
      • Cancer Care Associates - Midtown Tulsa
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center - Philadelphia
    • Reading, Pennsylvania, United States, 19612-6052
      • McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
  • Texas
    • Galveston, Texas, United States, 77555-0361
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response	Per GOG Response Evaluation Criteria In Solid Tumors(RECIST) Criteria: Complete Response(CR): disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial Response(PR): 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 nontarget lesions and no new lesions. Increasing Disease: at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Stable Disease: any condition not meeting the above criteria. Indeterminate for response: as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease.	up to 6 months from study entry

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival and Overall Survival at 6 Months After Completion of Treatment	up to 5 years from study entry

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: Bristol-Myers Squibb; National Cancer Institute (NCI)
• Investigators: Study Chair: John H. Farley, MD, Uniformed Services University of the Health Sciences

Publications and helpful links

General Publications

• Farley J, Sill MW, Birrer M, Walker J, Schilder RJ, Thigpen JT, Coleman RL, Miller BE, Rose PG, Lankes HA. Phase II study of cisplatin plus cetuximab in advanced, recurrent, and previously treated cancers of the cervix and evaluation of epidermal growth factor receptor immunohistochemical expression: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 May 1;121(2):303-8. doi: 10.1016/j.ygyno.2011.01.030. Epub 2011 Feb 16.

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: January 7, 2005
• First Submitted That Met QC Criteria: January 7, 2005
• First Posted (Estimate): January 10, 2005

Study Record Updates

• Last Update Posted (Estimate): March 17, 2014
• Last Update Submitted That Met QC Criteria: February 3, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: cervical squamous cell carcinoma; stage III cervical cancer; stage IVA cervical cancer; recurrent cervical cancer; stage IVB cervical cancer; cervical adenocarcinoma; cervical adenosquamous cell carcinoma; cervical small cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: GOG-0076DD; BMS-CA225-075; CDR0000405839