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

• Sponsor: University of Medicine and Dentistry of New Jersey (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00138151
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 33
• Locations: 6
• Arm: 1
• Duration (Months): 116
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Biological: recombinant interferon alpha-2b; Drug: isotretinoin; Drug: paclitaxel	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Chemosensitization With Paclitaxel, 13-cis Retinoic Acid and Interferon Alpha-2b in Advanced Uterine Cervical Carcinoma
• Study Start Date: Mar 1, 2001
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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]

2. The Effect of the Regimen on Raf-1 Kinase Phosphorylation in Biopsy Specimens. [8 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey	United States	08690
2	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
3	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
4	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08903
5	UMDNJ University Hospital	Newark	New Jersey	United States	07103
6	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Medicine and Dentistry of New Jersey
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lorna Rodriguez, MD, PhD, Rutgers Cancer Institute of New Jersey

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Medicine and Dentistry of New Jersey
• ClinicalTrials.gov Identifier: NCT00138151
• Other Study ID Numbers: CDR0000433516; P30CA072720; CINJ-100101; CINJ-3390; CINJ-NJ1703
• First Posted: Aug 30, 2005
• Last Update Posted: Nov 20, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by University of Medicine and Dentistry of New Jersey: recurrent cervical cancer; stage IVB cervical cancer
• Additional relevant MeSH terms: Uterine Cervical Neoplasms; Interferons; Interferon-alpha; Interferon alpha-2; Paclitaxel; Isotretinoin

Study Results

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.

Arm/Group Title	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
Arm/Group Description	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
Period Title: Overall Study
STARTED	33
COMPLETED	29
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
Arm/Group Description	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
Overall Participants	33
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 84.8%
>=65 years	5 15.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.2 (12.7)
Sex: Female, Male (Count of Participants)
Female	33 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	33 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Study was closed prematurely due to slow accrual and lack of study drug. Insufficient accrual to evaluate response rate.

Arm/Group Title	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
Arm/Group Description	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
Measure Participants	0

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Study was closed prematurely due to slow accrual and lack of study drug. Insufficient accrual to evaluate response rate.

Arm/Group Title	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
Arm/Group Description	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
Measure Participants	0

3. Secondary Outcome

Title	The Effect of the Regimen on Raf-1 Kinase Phosphorylation in Biopsy Specimens.
Time Frame	8 years

Outcome Measure Data

Analysis Population Description

Study was closed prematurely due to slow accrual and lack of study drug. Insufficient accrual to evaluate response rate.

Arm/Group Title	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
Arm/Group Description	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
Measure Participants	0

Adverse Events

Time Frame	8 years
Arm/Group Title	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
Arm/Group Description	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
All Cause Mortality
	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
	Affected / at Risk (%)	# Events
Total	18/33 (54.5%)
Blood and lymphatic system disorders
Thrombosis/embolism	2/33 (6.1%)	2
Hemoglobin	3/33 (9.1%)	6
Vaginal bleeding	1/33 (3%)	1
Hematuria (in the absence of vaginal bleeding)	1/33 (3%)	1
Rectal bleeding/hematochezia	1/33 (3%)	1
Cardiac disorders
Hypertension	1/33 (3%)	1
Congestive heart failure	1/33 (3%)	2
Gastrointestinal disorders
Dehydration	2/33 (6.1%)	2
Vomiting	2/33 (6.1%)	2
General disorders
Abdominal pain	3/33 (9.1%)	3
Fatigue	1/33 (3%)	1
Fever in the absence of neutropenia where neutropenia is defined as AGC <1.0 x 10e9/L	4/33 (12.1%)	4
Pain (other) - back pain	4/33 (12.1%)	5
Death	1/33 (3%)	1
Rigors/chills	1/33 (3%)	1
Infections and infestations
Infection without neutropenia	8/33 (24.2%)	9
Infection/Febrile Neutropenia	1/33 (3%)	1
Investigations
Hyponatremia	2/33 (6.1%)	2
Hyperkalemia	1/33 (3%)	1
Hypocalcemia	1/33 (3%)	1
Elevated ammonia level	1/33 (3%)	1
Hypokalemia	2/33 (6.1%)	2
Hypomagnesemia	1/33 (3%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness (not due to neuropathy)	1/33 (3%)	1
Fracture - neck	1/33 (3%)	1
Cervical spinal cord compression	1/33 (3%)	1
Nervous system disorders
Depressed level of consciousness - somnolence	1/33 (3%)	1
Dizziness	1/33 (3%)	1
Change in mental status	1/33 (3%)	1
Psychiatric disorders
Mood alteration - anxiety, agitation	1/33 (3%)	2
Hallucinations	1/33 (3%)	1
Renal and urinary disorders
Fistula or GU fistula (e.g., vaginal, vesicovaginal)	1/33 (3%)	1
Ureteral obstruction	1/33 (3%)	1
Dysuria	1/33 (3%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates	2/33 (6.1%)	2
Dypsnea	1/33 (3%)	1
Hypoxia	1/33 (3%)	1
Pulmonary other - respiratory failure	1/33 (3%)	1
Vascular disorders
Edema	2/33 (6.1%)	2
Other (Not Including Serious) Adverse Events
	Paclitaxel, 13-cis Retinoic Acid, and Interferon Alpha-2b
	Affected / at Risk (%)	# Events
Total	30/33 (90.9%)
Blood and lymphatic system disorders
Hemoglobin	9/33 (27.3%)	16
Neutrophils/granulocytes (ANC/AGC)	9/33 (27.3%)	33
Leukocytes (total WBC)	7/33 (21.2%)	28
Blood/Bone Marrow-Other (Specify,_____)	3/33 (9.1%)	4
Neutrophils/granulocytes (ANC/AGC) for BMT studies, if specified in the protocol	2/33 (6.1%)	2
Cardiac disorders
Hypertension	2/33 (6.1%)	2
Endocrine disorders
Hot flashes/flushes	3/33 (9.1%)	3
Gastrointestinal disorders
Nausea	16/33 (48.5%)	33
Vomiting	12/33 (36.4%)	15
Diarrhea, patients without colostomy	11/33 (33.3%)	15
Constipation	10/33 (30.3%)	13
Anorexia	7/33 (21.2%)	9
Gastrointestinal - other	6/33 (18.2%)	6
Dehydration	3/33 (9.1%)	3
Stomatitis/pharyngitis (oral/pharyngeal mucositis)	2/33 (6.1%)	2
Stomatitis/pharyngitis (oral/pharyngeal mucositis) for BMT studies, if specified in the protocol	2/33 (6.1%)	2
Abdominal pain or cramping	6/33 (18.2%)	6
General disorders
Fatigue (lethargy, malaise, asthenia)	19/33 (57.6%)	31
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L)	16/33 (48.5%)	24
Rigors, chills	8/33 (24.2%)	13
Constitutional Symptoms-Other (Specify,_____)	4/33 (12.1%)	6
Pain-Other (Specify,___)	17/33 (51.5%)	31
Headache	7/33 (21.2%)	8
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	2/33 (6.1%)	2
Infections and infestations
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	2/33 (6.1%)	2
Infection without neutropenia	2/33 (6.1%)	3
Infection/Febrile Neutropenia-Other (Specify,____)	2/33 (6.1%)	3
Investigations
Hypertriglyceridemia	3/33 (9.1%)	3
Hypercholesterolemia	2/33 (6.1%)	2
Hyperglycemia	2/33 (6.1%)	2
Hyperuricemia	2/33 (6.1%)	2
Hypokalemia	2/33 (6.1%)	2
Musculoskeletal and connective tissue disorders
Myalgia (muscle pain)	6/33 (18.2%)	9
Arthralgia (joint pain)	4/33 (12.1%)	5
Bone pain	3/33 (9.1%)	4
Muscle weakness (not due to neuropathy)	3/33 (9.1%)	3
Musculoskeletal-Other (Specify,______)	3/33 (9.1%)	4
Nervous system disorders
Neuropathy-sensory	10/33 (30.3%)	17
Dizziness/lightheadedness	3/33 (9.1%)	3
Insomnia	3/33 (9.1%)	3
Neurology-Other (Specify,______)	2/33 (6.1%)	2
Psychiatric disorders
Mood alteration-anxiety, agitation	4/33 (12.1%)	4
Mood alteration-depression	4/33 (12.1%)	4
Renal and urinary disorders
Renal/Genitourinary-Other (Specify,____)	4/33 (12.1%)	4
Urinary frequency/urgency	4/33 (12.1%)	5
Dysuria (painful urination)	2/33 (6.1%)	2
Ureteral obstruction	2/33 (6.1%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	5/33 (15.2%)	9
Skin and subcutaneous tissue disorders
Alopecia	19/33 (57.6%)	22
Dermatology/Skin-Other (Specify,_____)	3/33 (9.1%)	6
Nail changes	2/33 (6.1%)	2
Rash/desquamation	2/33 (6.1%)	2
Vascular disorders
Edema	6/33 (18.2%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.