ABI-007 in Treating Patients With Persistent or Recurrent Cervical Cancer

OBJECTIVES:

I. Estimate the antitumor activity of ABI-007 in patients with persistent or recurrent
squamous or nonsquamous cell carcinoma of the cervix who have failed on higher-priority
treatment protocols.

II. Determine the nature and degree of toxicity of ABI-007 in this cohort of patients.

III. To determine the expression of the SPARC (secreted protein, acidic and rich in cysteine)
protein in the tumor tissue and plasma (exploratory study) of patients treated with this
regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive ABI-007 IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28
days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for SPARC protein
expression analysis by ELISA. Archived tumor tissue samples are also analyzed.

After completion of study treatment, patients are followed periodically for up to 5 years.

Inclusion Criteria:

- Persistent or recurrent squamous or nonsquamous cell carcinoma of the cervix with
documented disease progression

- Histologic confirmation of the original primary tumor

- Measurable disease, defined as at least one target lesion that can be accurately
measured in at least one dimension ≥ 20 mm when measured by conventional techniques,
including palpation, plain x-ray, CT scan, or MRI, or ≥ 10 mm when measured by spiral
CT scan

- 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 after completion of radiotherapy

- Must have received 1 prior systemic chemotherapeutic regimen for management of
advanced, metastatic, or recurrent squamous or nonsquamous cell carcinoma of the
cervix

- Chemotherapy administered as a radiosensitizer is not a systemic chemotherapy
regimen

- Not eligible for a higher priority GOG protocol

- GOG performance status 0, 1, or 2

- No active infection requiring antibiotics

- Platelet count ≥ 100,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- SGOT and alkaline phosphatase ≤ 2.5 times ULN

- No neuropathy (sensory and motor) > grade 1

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No evidence of any other invasive malignancies within the past 3-5 years, except
localized breast cancer, head and neck cancer, cervical cancer, or nonmelanoma skin
cancer

- No pre-existing hearing loss/tinnitus > grade 1

- No concurrent amifostine or other protective agents

- Recovered from effects of prior surgery, radiotherapy, or chemotherapy

- Hormonal therapy directed at malignant tumor must be discontinued at least 1 week
prior to study entry

- Continuation of hormone replacement therapy permitted

- At least 3 weeks since prior biological therapy and immunotherapy

- No more than 1 prior cytotoxic chemotherapy regimen (either with single or combination
cytotoxic drug therapy)

- May have received 1 additional noncytotoxic (biologic or cytostatic) regimen,
including monoclonal antibodies, cytokines, or small-molecule inhibitors of
signal transduction

- No prior radiotherapy to any portion of the abdominal cavity or pelvis

- Radiotherapy for the treatment of cervical cancer within the past 5 years allowed

- Radiotherapy for localized breast cancer, head and neck or skin allowed provided
completion > 3 years prior to study entry and remains free of recurrent or
metastatic disease

- No prior chemotherapy for any abdominal or pelvic tumor

- Chemotherapy for the treatment of cervical cancer within the past 5 years allowed

- Prior adjuvant chemotherapy for localized breast cancer provided completion > 3
years prior to study entry and remains free of recurrent or metastatic disease

- No prior therapy with ABI-007 or any other taxane

- No prior anticancer treatment that would preclude study therapy

- No concurrent ritonavir, saquinavir, indinavir, nelfinavir, or anticonvulsants