Cervical Cancer
Conditions
Keywords
recurrent cervical cancer, stage IVB cervical cancer
Brief summary
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
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.
Interventions
BIOLOGICALrecombinant interferon alpha-2b
Interferon alpha-2b at a dose of 6 mU/m2 SQ qd days 1-4 of each cycle
DRUGisotretinoin
Cis-retinoic acid at a dose of 1 mg/kg/day PO qd days 1-4 of each cycle
DRUGpaclitaxel
Paclitaxel 175 mg/m2 will be given on day 4. Cycles will be repeated every 21 days
Sponsors
National Cancer Institute (NCI)
University of Medicine and Dentistry of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete and Partial) | 8 years | All patients who receive at least 3 courses of protocol therapy will be considered evaluable for response of measurable disease. |
Secondary
| Measure | 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 |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 4 sites across New Jersey (2 academic medical centers and 2 community hospitals) from March 2001 through June 2009.
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b * 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 | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age Continuous | 53.2 years STANDARD_DEVIATION 12.7 |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 33 |
| serious Total, serious adverse events | 18 / 33 |
Outcome results
Primary
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.
Time frame: 8 years
Population: Study was closed prematurely due to slow accrual and lack of study drug. Insufficient accrual to evaluate response rate.
Secondary
The Effect of the Regimen on Bcl-2 Family Proteins in Biopsy Specimens and Correlation With Peripheral Blood Mononuclear Cell Bcl-2 Levels.
Time frame: 8 years
Population: Study was closed prematurely due to slow accrual and lack of study drug. Insufficient accrual to evaluate response rate.
Secondary
The Effect of the Regimen on Raf-1 Kinase Phosphorylation in Biopsy Specimens.
Time frame: 8 years
Population: Study was closed prematurely due to slow accrual and lack of study drug. Insufficient accrual to evaluate response rate.