Clinical trial NCT00003377: Radiation Therapy, Paclitaxel, and Cisplatin in Treating Patients With Cancer of the Cervix
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cervical Cancer
Keywords: stage III cervical cancer
stage IVA cervical cancer
cervical squamous cell carcinoma
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 29
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment
timeFrame: up to 21 weeks
Secondary outcomes:
measure: Disease-free Survival at 2 Years
timeFrame: 2 years
measure: Overall Survival at 2 Years
timeFrame: 2 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Camden
country: United States
facility: Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
state: New Jersey
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth's Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center at Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Associates - Midtown Tulsa
state: Oklahoma
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Oklahoma University Cancer Institute
name: Joan L. Walker, MD
role: STUDY_CHAIR
References:
citation: Walker JL, Morrison A, DiSilvestro P, von Gruenigen VE; Gynecologic Oncology Group. A phase I/II study of extended field radiation therapy with concomitant paclitaxel and cisplatin chemotherapy in patients with cervical carcinoma metastatic to the para-aortic lymph nodes: a Gynecologic Oncology Group study. Gynecol Oncol. 2009 Jan;112(1):78-84. doi: 10.1016/j.ygyno.2008.09.035. Epub 2008 Nov 17.