Clinical trial NCT00499031: Cetuximab in Treating Patients With Persistent or Recurrent Cervical Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Squamous Cell Carcinoma
Recurrent Cervical Carcinoma
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-07-11
Enrollment: 38
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Progression-free Survival Greater Than 6 Months
timeFrame: At 6 months
measure: Objective Tumor Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: every other cycle for the first 6 months; then every 3 months x 2; then every 6 months
Secondary outcomes:
measure: Duration of Progression-free Survival
timeFrame: From study entry until disease progression, death or date of last contact, up to 5 years
measure: Duration of Objective Response Rate
timeFrame: Up to 5 years
measure: Frequency and Severity of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
timeFrame: Up to 5 years
measure: Duration of Overall Survival
timeFrame: From study entry to death or the date of last contact, up to 5 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Colorado Gynecologic Oncology Group
state: Colorado
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Services
state: Indiana
city: Pascagoula
country: United States
facility: Singing River Hospital
state: Mississippi
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Brightwaters
country: United States
facility: Island Gynecologic Oncology
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Associates-Midtown
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Cancer Institute
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Anderson
country: United States
facility: AnMed Health Hospital
state: South Carolina
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Gynecologic Oncology Group
name: Alessandro Santin
role: PRINCIPAL_INVESTIGATOR
References: