Cetuximab in Treating Patients With Persistent or Recurrent Cervical Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00499031
First received: July 10, 2007
Last updated: May 22, 2014
Last verified: September 2013
  Purpose

This phase II trial is studying cetuximab to see how well it works in treating patients with persistent or recurrent cervical cancer. 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.


Condition Intervention Phase
Cervical Squamous Cell Carcinoma
Recurrent Cervical Cancer
Biological: cetuximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Cetuximab (Erbitux®, C225, NSC# 714692) in the Treatment of Persistent or Recurrent Squamous or Non-Squamous Cell Carcinoma of the Cervix

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Progression-free Survival Greater Than 6 Months [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
  • Objective Tumor Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: every other cycle for the first 6 months; then every 3 months x 2; then every 6 months ] [ Designated as safety issue: No ]

    Response is measured according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0):

    Complete Response (CR) is 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) is 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.

    Disease Progression is 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 is any condition not meeting the above criteria.

    Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease.



Secondary Outcome Measures:
  • Duration of Progression-free Survival [ Time Frame: From study entry until disease progression, death or date of last contact, up to 5 years ] [ Designated as safety issue: No ]
  • Duration of Objective Response Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Frequency and Severity of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Duration of Overall Survival [ Time Frame: From study entry to death or the date of last contact, up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: June 2007
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cetuximab)
Patients receive cetuximab IV over 120 minutes on day 1.
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the activity of cetuximab for patients with persistent or recurrent carcinoma of the cervix.

II. To determine the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response.

SECONDARY OBJECTIVES:

I. To characterize the distribution of progression-free survival and overall survival.

II. To determine the effect of cetuximab on the duration of objective response in persistent or recurrent carcinoma of the cervix.

III. To determine the nature and degree of toxicity of cetuximab as assessed by CTCAE v3.0 in this cohort of patients.

OUTLINE:

Patients receive cetuximab IV over 120 minutes on day 1. Courses repeat once weekly in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed (with physical exams and histories) every three months for the first two years and then every six months for the next three years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion criteria:

    • Patients must have persistent or recurrent squamous or non-squamous cell carcinoma of the cervix with documented disease progression (disease not amenable to curative therapy)

      • Histologic documentation of the original primary tumor is required via the pathology report
    • All patients must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded)

      • Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT scan, and MRI, OR ≥ 10 mm when measured by spiral CT scan
    • Patients must have at least one target lesion to be used to assess response on this protocol

      • Tumors within a previously irradiated field will be designated as nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
    • Patients must have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent carcinoma of the cervix

      • Chemotherapy administered in conjunction with primary radiation as a radiosensitizer is not counted as a systemic chemotherapy regimen
    • Patients must not be eligible for a higher priority GOG protocol, if one exists

      • In general, this would refer to any active GOG phase III protocol for the same patient population
  • Exclusion criteria:

    • Patients with craniospinal metastases
  • Inclusion criteria:

    • Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2 or patients who have received two prior regimens must have a GOG performance status of 0 or 1
    • Patients should be free of active infection requiring antibiotics
    • Platelet count ≥ 100,000/μl
    • ANC ≥ 1,500/μl
    • Creatinine ≤ 1.5 x institutional upper limit normal (ULN)
    • Bilirubin ≤ 1.5 x ULN
    • SGOT and alkaline phosphatase ≤ 2.5 x ULN
    • Neuropathy (sensory and motor) ≤ CTCAE v3.0 grade 1
    • Calcium < 11.0 mg/dL
    • Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiating protocol therapy and be practicing an effective form of contraception during protocol therapy and for at least two months following completion of protocol therapy
  • Exclusion criteria:

    • Patients with a history of other invasive malignancies, with the exception of nonmelanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last five years

      • Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
    • Patients who have a significant history of cardiac disease (i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure, or uncontrolled arrhythmias) within 6 months of registration
    • Patients who have an uncontrolled seizure disorder or active neurological disease
    • Patients known to be seropositive for HIV and active hepatitis, even if liver function studies are in the eligible range
    • Pregnant or nursing women or women of childbearing potential unless using effective contraception as determined by the investigator
    • Known hemorrhagic diathesis or active bleeding disorder
  • Inclusion criteria:

    • Recovery from effects of recent surgery, radiotherapy, or chemotherapy

      • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration (continuation of hormone replacement therapy is permitted)
      • Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration
    • Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent cervical disease according to the following definition:

      • Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
    • Patients must not have received any non-cytotoxic therapy for management of recurrent or persistent cervical disease
    • Patients must not be receiving any other investigational agent
  • Exclusion criteria:

    • Patients who have received prior therapy with cetuximab or any other anti-epidermal growth factor receptor antibody
    • Patients who have received any prior therapy with a tyrosine kinase inhibitor that targets the EGFR pathway
    • Patients who have received prior chimerized or murine monoclonal antibody therapy
    • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of cervical cancer within the last five years are excluded

      • Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration and the patient remains free of recurrent or metastatic disease
    • Patients who have received prior chemotherapy for any abdominal or pelvic tumor other than for the treatment of cervical cancer within the last five years are excluded

      • Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration and that the patient remains free of recurrent or metastatic disease
    • Patients who have undergone major surgery, excluding diagnostic biopsy, within 30 days (to allow for full recovery) prior to registration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499031

  Show 22 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Principal Investigator: Alessandro Santin Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00499031     History of Changes
Other Study ID Numbers: GOG-0227E, NCI-2009-00596, BMS-CA225-275, CDR0000554455, GOG-0227E, GOG-0227E, U10CA027469
Study First Received: July 10, 2007
Results First Received: May 22, 2014
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Uterine Cervical Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Antibodies
Antibodies, Monoclonal
Cetuximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014