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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cervical Cancer
• Intervention / Treatment: Biological: recombinant interferon alpha-2b; Drug: isotretinoin; Drug: paclitaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hamilton, New Jersey, United States, 08690
      • Cancer Institute of New Jersey at Hamilton
    • Morristown, New Jersey, United States, 07962
      • Carol G. Simon Cancer Center at Morristown Memorial Hospital
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • New Brunswick, New Jersey, United States, 08903
      • Saint Peter's University Hospital
    • Newark, New Jersey, United States, 07103
      • UMDNJ University Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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	Biological: recombinant interferon alpha-2b; Interferon alpha-2b at a dose of 6 mU/m2 SQ qd days 1-4 of each cycle; Drug: isotretinoin; Cis-retinoic acid at a dose of 1 mg/kg/day PO qd days 1-4 of each cycle; Drug: paclitaxel; Paclitaxel 175 mg/m2 will be given on day 4. Cycles will be repeated every 21 days

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lorna Rodriguez, MD, PhD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): November 1, 2010

Study Registration Dates

• First Submitted: August 29, 2005
• First Submitted That Met QC Criteria: August 29, 2005
• First Posted (ESTIMATE): August 30, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): November 20, 2013
• Last Update Submitted That Met QC Criteria: September 17, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: recurrent cervical cancer; stage IVB cervical cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Dermatologic Agents; Interferons; Interferon-alpha; Paclitaxel; Interferon alpha-2; Isotretinoin
• Other Study ID Numbers: CDR0000433516; P30CA072720 (U.S. NIH Grant/Contract); CINJ-100101 (OTHER: Cancer Institute of New Jersey); CINJ-3390 (OTHER: Cancer Institute of New Jersey); CINJ-NJ1703 (OTHER: Cancer Institute of New Jersey)