Radiation Therapy and Chemotherapy in Treating Patients With Locally Advanced Cervical Cancer

A PHASE I STUDY OF PELVIC RADIATION THERAPY WITH CONCOMITANT WEEKLY CISPLATIN AND TOPOTECAN CHEMOTHERAPY IN PATIENTS WITH CERVICAL CARCINOMA WITHOUT EXTRA-PELVIC METASTASIS

This phase I trial is studying the side effects and best way to give radiation therapy when given together with topotecan and cisplatin in treating patients with locally advanced cervical cancer. This trial is also studying the best dose of topotecan when given in this regimen. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as topotecan and cisplatin, 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.

Study Overview

• Status: Completed
• Conditions: Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer
• Intervention / Treatment: Drug: Cisplatin; Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Topotecan Hydrochloride Liposomes

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of pelvic radiotherapy, cisplatin, and topotecan in patients with locally advanced cervical cancer.

II. Determine the maximum tolerated dose (MTD) of topotecan when administered in this regimen in this patient population.

SECONDARY OBJECTIVES:

I. Determine the site of recurrence (local vs distant) in patients treated with this regimen.

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

Patients undergo radiotherapy 5 days a week for 6 weeks. Patients receive cisplatin IV and topotecan IV over 30 minutes once weekly for a total of 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experiences dose-limiting toxicity. Once the MTD is determined, an additional cohort of 20 patients receives treatment as above at the MTD.

After completion of study treatment, patients are followed periodically for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Tulsa Cancer Institute
    • Tulsa, Oklahoma, United States, 74104
      • Cancer Care Associates-Midtown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed primary invasive carcinoma of the uterine cervix

  • Stages IB2, II, IIIB, and IVA disease
  • Any cell type
• No known metastasis to scalene nodes or organs outside the radiation field
• No known intraperitoneal metastases
• No evidence of extrapelvic disease based on negative CT or PET scan
• Must enroll within 8 weeks of diagnosis
• Performance status - GOG 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine normal
• Creatinine clearance > 50 mL/min
• Prior ureteral obstruction allowed provided stent or nephrostomy tube has been placed
• No renal abnormalities, such as pelvic kidney, horseshoe kidney, or prior renal transplantation that would require modification of radiation fields
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No septicemia or severe infection
• No other medical or psychiatric condition that would preclude study compliance
• No prior chemotherapy for any prior malignancy
• No prior cytotoxic chemotherapy for this malignancy
• No prior radiotherapy for any prior malignancy
• No prior pelvic or abdominal radiotherapy for this malignancy
• No prior therapy for this malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (topotecan hydrochloride, radiation, cisplatin); Patients undergo radiotherapy 5 days a week for 6 weeks. Patients receive cisplatin IV and topotecan IV over 30 minutes once weekly for a total of 6 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Cisplatin; Given IV; Radiation: 3-Dimensional Conformal Radiation Therapy; Other Names: 3D-CRT; Conformal Therapy; Radiation Conformal Therapy; Drug: Topotecan Hydrochloride Liposomes; Given IV; Other Names: Brakiva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of patients with acute toxicity assessed by Common Terminology Criteria for Adverse Events version 3.0	Up to 30 days after completion of radiation therapy
Incidence of patients with chronic toxicity assessed by Common Toxicity Criteria Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (CTC RTOG/EORTC)	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Site of treatment failure	Identified as local versus distant.	Up to 5 years

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Peter Rose, Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: February 5, 2003
• First Submitted That Met QC Criteria: February 5, 2003
• First Posted (Estimate): February 6, 2003

Study Record Updates

• Last Update Posted (Estimate): December 31, 2014
• Last Update Submitted That Met QC Criteria: December 29, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Cisplatin; Topotecan
• Other Study ID Numbers: GOG-9913 (Other Identifier: CTEP); U10CA027469 (U.S. NIH Grant/Contract); NCI-2009-00617 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000270680