Radiation Therapy, Paclitaxel, and Cisplatin in Treating Patients With Cancer of the Cervix

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00003377
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 29
• Locations: 13
• Arm: 1
• Duration (Months): 116
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Paclitaxel and cisplatin may increase the effectiveness of radiation therapy by making the tumor cells more sensitive to the radiation. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of paclitaxel when given with radiation therapy and cisplatin and to see how well they work in treating patients with cancer of the cervix that has spread to the lymph nodes in the pelvis and abdomen.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Drug: cisplatin; Drug: paclitaxel; Radiation: brachytherapy; Radiation: radiation therapy	Phase 1

Detailed Description

OBJECTIVES:

• Determine the toxicity of extended field radiotherapy with concurrent paclitaxel and cisplatin chemotherapy (as radiation sensitization) in patients with previously untreated carcinoma of the cervix metastatic to the para-aortic lymph nodes.

• Determine the maximum tolerated dose of paclitaxel when combined with cisplatin plus extended field radiotherapy in this patient population.

• Determine the effect of this treatment regimen on progression-free survival, overall survival, and site of recurrence (local vs distant) in these patients.

OUTLINE: This is a multicenter, dose-escalation study of paclitaxel.

Patients receive external beam radiotherapy (RT) to the para-aortic nodes and the pelvis daily for 5 weeks; RT must be completed within 8 weeks of its initiation. During or after external beam RT, intracavitary radiation is administered 1-5 times. Concurrently with external beam RT, patients receive paclitaxel IV over 1 hour followed immediately by cisplatin IV on days 1, 8, 15, 22, 29, and 36.

Cohorts of 3-6 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter or until the time of recurrence or death.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 4 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of Extended Field Radiation Therapy With Concomitant Paclitaxel and Cisplatin Chemotherapy in Patients Cervical Carcinoma Metastatic to the Para-Aortic Lymph Nodes
• Study Start Date: Nov 1, 1999
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Radiation therapy plus concurrent weekly chemotherapy	Drug: cisplatin; Drug: paclitaxel; Radiation: brachytherapy; Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

1. Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment [up to 21 weeks]

Secondary Outcome Measures

1. Disease-free Survival at 2 Years [2 years]

   Product-limit estimate of the probability of being alive and progression-free at 24 months based on those 20 patients who were treated at the study recommended dose level (RDL) is 0.65, 95% confidence interval (0.44-0.86). Progression is defined as a 50% or greater increase in the product from any lesion documented within eight weeks for study entry or the appearance of any new lesion within eight weeks of entry into study.

2. Overall Survival at 2 Years [2 years]

   Product-limit estimate of the probability of being alive at 24 months based on those 20 patients who were treated at the study recommended dose-level is 0.80, 95 % confidence interval (0.62-0.97)

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically proven previously untreated invasive carcinoma of the uterine cervix

• Squamous cell carcinoma

• Adenosquamous carcinoma

• Adenocarcinoma

• TNM classification stage IIIB or IVA (FIGO classification stage IB, IIA, IIB, IIIA, IIIB, or IVA)

• Cytologically or histologically proven metastases to the para-aortic lymph nodes

• No more than 8 weeks since diagnosis

• No metastases to scalene nodes, intraperitoneal metastases, or metastases to other organs outside the radiation field at the time of original clinical and surgical staging

• Negative CT scan of the chest

• Patients with ureteral obstruction must be treated with stent or nephrostomy tube

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• GOG 0-2

Life expectancy:

• At least 6 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times normal

• SGOT no greater than 3 times normal

Renal:

• Creatinine less than 2.0 mg/dL

• No renal abnormalities (e.g., pelvic kidney, horseshoe kidney, or renal transplantation) requiring modification of radiation fields

Other:

• Not pregnant

• No septicemia or severe infection

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior cytotoxic chemotherapy for this or other malignancy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for this or other malignancy

• No prior radiotherapy to pelvis or abdomen

Surgery:

• Not specified

Other:

• No other prior therapy for this malignancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
2	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
3	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242
4	Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees	Camden	New Jersey	United States	08103
5	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157
6	MetroHealth's Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
7	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio	United States	44111
8	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
9	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio	United States	43210
10	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214
11	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
12	Cancer Care Associates - Midtown Tulsa	Tulsa	Oklahoma	United States	74104
13	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Joan L. Walker, MD, Oklahoma University Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00003377
• Other Study ID Numbers: CDR0000066371; GOG-9804
• First Posted: Jan 27, 2003
• Last Update Posted: Feb 4, 2013
• Last Verified: Dec 1, 2012

• Keywords provided by Gynecologic Oncology Group: stage III cervical cancer; stage IVA cervical cancer; cervical squamous cell carcinoma; cervical adenocarcinoma; cervical adenosquamous cell carcinoma
• Additional relevant MeSH terms: Uterine Cervical Neoplasms; Paclitaxel; Cisplatin

Study Results

Participant Flow

Recruitment Details	In Period I 12 patients were treated with weekly cisplatin(30-40 mg/m2) and paclitaxel(30-50 mg/m2) concurrent with extended field radiation. In Period II an additional 17 patients were treated with cisplatin 40 mg/m2 and paclitaxel 40 mg/m2 concurrent with radiation.
Pre-assignment Detail	All patients received whole pelvic and extended field radiation at 150 centigray per day for 30 days to the para-aortics, and 180 centigray per day for 25 days to the pelvis.

Arm/Group Title	Arm 1, P I	Arm 2, P I	Arm 3, P I	Arm 4, P I	Arm 2, P II
Arm/Group Description	Cisplatin 40 mg/m2, plus Paclitaxel 30 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 50 mg/m2	Cisplatin 30 mg/m2, plus Paclitaxel 50 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2
Period Title: Period I
STARTED	3	3	3	3	0
COMPLETED	3	3	2	2	0
NOT COMPLETED	0	0	1	1	0
Period Title: Period I
STARTED	0	0	0	0	17
COMPLETED	0	0	0	0	16
NOT COMPLETED	0	0	0	0	1

Baseline Characteristics

Arm/Group Title	Arm 1, P I	Arm 2, P I	Arm 2, P II	Arm 3, P I	Arm 4, P I	Total
Arm/Group Description	Cisplatin 40 mg/m2, plus Paclitaxel 30 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 50 mg/m2	Cisplatin 30 mg/m2, plus Paclitaxel 50 mg/m2	Total of all reporting groups
Overall Participants	3	3	17	3	3	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.4 (13.7)	54.2 (10.7)	49.8 (11.0)	47.6 (8.4)	47.7 (4.0)	49.5 (10.1)
Age, Customized (participants) [Number]
20-29 years	0 0%	0 0%	1 5.9%	0 0%	0 0%	1 3.4%
30-39 years	1 33.3%	0 0%	1 5.9%	0 0%	0 0%	2 6.9%
40-49 years	1 33.3%	1 33.3%	9 52.9%	2 66.7%	2 66.7%	15 51.7%
50-59 years	0 0%	1 33.3%	2 11.8%	1 33.3%	1 33.3%	5 17.2%
60-69 years	1 33.3%	1 33.3%	4 23.5%	0 0%	0 0%	6 20.7%
Sex: Female, Male (Count of Participants)
Female	3 100%	3 100%	17 100%	3 100%	3 100%	29 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	17 100%	3 100%	3 100%	29 100%
FIGO (International Federation of Gynecology and Obstetrics) Stage (participants) [Number]
1A - disease identified only microscopically	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
1B - disease confined to cervix	1 33.3%	1 33.3%	2 11.8%	2 66.7%	0 0%	6 20.7%
2A - no obvious parametrial involvement	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
2B - obvious parametrial involvement	2 66.7%	0 0%	4 23.5%	0 0%	1 33.3%	7 24.1%
3A -disease in lower 3rd of vagina not pelvic wall	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
3B - disease extended to pelvic wall	0 0%	2 66.7%	7 41.2%	1 33.3%	2 66.7%	12 41.4%
4A - disease spread to adjacent organs	0 0%	0 0%	4 23.5%	0 0%	0 0%	4 13.8%
4B - disease spread to distant organs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Cell Type (participants) [Number]
Adenocarcinoma NOS(not otherwise specified)	0 0%	1 33.3%	1 5.9%	0 0%	0 0%	2 6.9%
Clear cell	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 3.4%
Squamous cell	3 100%	2 66.7%	16 94.1%	2 66.7%	3 100%	26 89.7%

Outcome Measures

1. Primary Outcome

Title	Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment
Time Frame	up to 21 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1, P I	Arm 2, P I	Arm 3, P I	Arm 4, P I	Arm 2, PII
Arm/Group Description	Cisplatin 40 mg/m2, plus Paclitaxel 30 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 50 mg/m2	Cisplatin 30 mg/m2, plus Paclitaxel 50 mg/m2	Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2
Measure Participants	3	3	3	3	17
Dose Limiting Toxicity(DLT)/Significant Dose Delay	0 0%	0 0%	2 11.8%	2 66.7%	0 0%
Complications unrelated to treatment	0 0%	0 0%	0 0%	0 0%	1 33.3%

2. Secondary Outcome

Title	Disease-free Survival at 2 Years
Description	Product-limit estimate of the probability of being alive and progression-free at 24 months based on those 20 patients who were treated at the study recommended dose level (RDL) is 0.65, 95% confidence interval (0.44-0.86). Progression is defined as a 50% or greater increase in the product from any lesion documented within eight weeks for study entry or the appearance of any new lesion within eight weeks of entry into study.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 2, P I & II
Arm/Group Description	Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2
Measure Participants	20
Mean (95% Confidence Interval) [probability]	0.65

3. Secondary Outcome

Title	Overall Survival at 2 Years
Description	Product-limit estimate of the probability of being alive at 24 months based on those 20 patients who were treated at the study recommended dose-level is 0.80, 95 % confidence interval (0.62-0.97)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 2, P I & II
Arm/Group Description	Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2
Measure Participants	20
Mean (95% Confidence Interval) [probability]	0.80

Adverse Events

Arm/Group Title	Arm 1, P I		Arm 2, P I		Arm 3, P I		Arm 4, P I		Arm 2, P II
Arm/Group Description	Cisplatin 40 mg/m2, plus Paclitaxel 30 mg/m2		Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2		Cisplatin 40 mg/m2, plus Paclitaxel 50 mg/m2		Cisplatin 30 mg/m2, plus Paclitaxel 50 mg/m2		Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2
All Cause Mortality
	Arm 1, P I		Arm 2, P I		Arm 3, P I		Arm 4, P I		Arm 2, P II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1, P I		Arm 2, P I		Arm 3, P I		Arm 4, P I		Arm 2, P II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		2/3 (66.7%)		1/17 (5.9%)
Cardiac disorders
Pulmonary disorders	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0
Gastrointestinal disorders
Nausea and vomiting	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/17 (0%)	0
Diarrhea	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1
Metabolism and nutrition disorders
Hypomagnesia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0
Hypocalcemia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Arm 1, P I		Arm 2, P I		Arm 3, P I		Arm 4, P I		Arm 2, P II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		2/3 (66.7%)		15/17 (88.2%)
Blood and lymphatic system disorders
Neutropenia	2/3 (66.7%)		0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		7/17 (41.2%)
Leukopenia	2/3 (66.7%)		3/3 (100%)		1/3 (33.3%)		1/3 (33.3%)		10/17 (58.8%)
Thrombocytopenia	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		2/17 (11.8%)
Anemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/17 (5.9%)
Cardiac disorders
Pulmonary Embolism	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/17 (5.9%)
Hypotension	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)
Gastrointestinal disorders
Nausea and vomiting	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		4/17 (23.5%)
Diarrhea	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		3/17 (17.6%)
General disorders
Fatigue	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		3/17 (17.6%)
Vaginal Bleeding	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)
Pelvic pain	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)
Abdominal pain	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)
Hepatobiliary disorders
ALT	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)
Infections and infestations
Febrile neutropenia	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		3/17 (17.6%)
Metabolism and nutrition disorders
Hypomagnesia	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/17 (0%)
Hypokalemia	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		3/17 (17.6%)
Hypocalcemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)
Hyperglycemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Weakness	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)
Nervous system disorders
Seizure	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/17 (0%)
Confusion	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/17 (0%)
Vascular disorders
Prothrombin time	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/17 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.