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

Study Overview
=================
Brief Summary
-----------------
This phase II trial is studying how well ABI-007 works in treating patients with persistent or recurrent cervical cancer. Drugs used in chemotherapy, such as ABI-007, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II Evaluation of ABI-007 in the Treatment of Persistent or Recurrent Squamous or Nonsquamous Cell Carcinoma of the Cervix

Conditions
-----------------
Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Small Cell Carcinoma, Cervical Squamous Cell Carcinoma, Recurrent Cervical Carcinoma

Intervention / Treatment
-----------------
* Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation
* Other: Laboratory Biomarker Analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
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
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (paclitaxel albumin-stabilized nanoparticle)<br>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. | Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation<br>* Given IV<br>* Other names: Abraxane;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as 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 non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. | CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; then every 3 months x 2; then every 6 months until disease progression for up to 5 years. | 
| Frequency and Severity of Observed Adverse Effects Assessed by Common Terminology Criteria for Adverse Events (CTCAE) |  | Up to 5 yearsAssessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up |