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

Inclusion Criteria

DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

- 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

PRIOR CONCURRENT THERAPY:

- 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