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

Cervical Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003377
• Other study ID #: CDR0000066371
• Secondary ID: GOG-9804
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: December 27, 2012
• Start date: November 1999
• Est. completion date: July 2009

Study information

• Verified date: December 2012
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• cisplatin

• paclitaxel

Radiation:
• brachytherapy

• radiation therapy

Locations

Country	Name	City	State
United States	Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees	Camden	New Jersey
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	MetroHealth's Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Cancer Care Associates - Midtown Tulsa	Tulsa	Oklahoma
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-ao — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Disease-free Survival at 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 years	No
Secondary	Overall Survival at 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)	2 years	No