Isotretinoin, Interferon Alpha-2b, and Paclitaxel in Stage IV, Recurrent, or Persistent Cervical Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving isotretinoin and interferon alpha-2b together with paclitaxel may reduce drug resistance and allow the tumor cells to be killed. PURPOSE: This phase II trial is studying how well giving isotretinoin and interferon alpha-2b together with paclitaxel works in treating patients with stage IV, recurrent, or persistent cervical cancer.

Detailed Description
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OBJECTIVES: Determine the response in patients with stage IVB, recurrent, or persistent cervical cancer treated with isotretinoin, interferon alpha-2b, and paclitaxel. OUTLINE: This is a multicenter study. Patients receive oral isotretinoin and interferon alpha-2b subcutaneously once daily on days 1-4 and paclitaxel IV over 3 hours on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 27-66 patients will be accrued for this study.

Official Title
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A Phase II Trial of Chemosensitization With Paclitaxel, 13-cis Retinoic Acid and Interferon Alpha-2b in Advanced Uterine Cervical Carcinoma

Conditions
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Cervical Cancer

Intervention / Treatment
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* Biological: recombinant interferon alpha-2b
* Drug: isotretinoin
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically and/or cytologically confirmed cervical cancer, meeting 1 of the following criteria: Stage IVB disease Recurrent disease Persistent disease Patients previously treated with chemoradiotherapy as initial therapy must demonstrate disease progression Measurable disease by physical exam or radiographic studies Not amenable to chemoradiotherapy or surgery PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-2 Life expectancy At least 6 months Hematopoietic WBC ≥ 3,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic SGOT and SGPT ≤ 2 times upper limit of normal Bilirubin ≤ 1.5 mg/dL Renal Creatinine ≤ 1.5 mg/dL OR Creatinine clearance ≥ 50 mL/min Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known HIV positivity No active infection No medical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy No prior interferon No other concurrent immunotherapy Chemotherapy See Disease Characteristics At least 3 months since prior chemoradiotherapy (6 weeks for patients experiencing disease progression after completion of initial chemoradiotherapy) No other prior chemotherapy Endocrine therapy No concurrent hormonal therapy for cancer Radiotherapy See Disease Characteristics See Chemotherapy Recovered from prior radiotherapy No concurrent radiotherapy Surgery Recovered from prior surgery No concurrent surgery for cancer Other No prior retinoids No other concurrent anticancer therapy No other concurrent experimental agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b<br>Cis-retinoic acid at a dose of 1 mg/kg/day PO qd days 1-4 of each cycle Interferon alpha-2b at a dose of 6 mU/m2 SQ qd days 1-4 of each cycle Paclitaxel 175 mg/m2 will be given on day 4. Cycles will be repeated every 21 days | Biological: recombinant interferon alpha-2b<br>* Interferon alpha-2b at a dose of 6 mU/m2 SQ qd days 1-4 of each cycle<br>Drug: isotretinoin<br>* Cis-retinoic acid at a dose of 1 mg/kg/day PO qd days 1-4 of each cycle<br>Drug: paclitaxel<br>* Paclitaxel 175 mg/m2 will be given on day 4. Cycles will be repeated every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Complete and Partial) | All patients who receive at least 3 courses of protocol therapy will be considered evaluable for response of measurable disease. | 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Effect of the Regimen on Bcl-2 Family Proteins in Biopsy Specimens and Correlation With Peripheral Blood Mononuclear Cell Bcl-2 Levels. |  | 8 years | 
| The Effect of the Regimen on Raf-1 Kinase Phosphorylation in Biopsy Specimens. |  | 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent cervical cancer, stage IVB cervical cancer