Radiation Therapy Plus Cisplatin and Gemcitabine in Treating Patients With Cervical Cancer

A Phase I Study of Whole Pelvic Radiation Therapy With Concomitant Cisplatin and Gemcitabine Chemotherapy in Patients With Cervical Carcinoma (Stages I-IV) Limited to the Pelvis

This phase I trial is studying the side effects and best dose of gemcitabine when given together with radiation therapy and cisplatin in treating patients with cervical cancer that has not spread beyond the pelvis. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining cisplatin with gemcitabine may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Small 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; Drug: Gemcitabine Hydrochloride; Radiation: Internal Radiation Therapy; Radiation: Radiation Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the toxicity of pelvic radiotherapy and concurrent cisplatin and gemcitabine in patients with cervical carcinoma limited to the pelvis.

II. Determine the maximum tolerated dose (MTD) of gemcitabine in combination with cisplatin and pelvic radiotherapy in these patients.

SECONDARY OBJECTIVES:

I. Determine the progression-free and overall survival of patients treated with gemcitabine at the MTD in this regimen.

II. Determine the site of recurrence, local versus distant, in patients treated with this regimen.

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

Patients receive gemcitabine IV over 30 minutes and cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36 in the absence of disease progression or unacceptable toxicity. Patients also undergo external whole pelvis radiotherapy once daily on days 1-5, 8-13, 15-20, 22-27, and 29-34. After completion of external beam radiotherapy, patients undergo intracavitary radiotherapy and parametrial radiotherapy. The total elapsed time for completion of all radiotherapy is not more than 8 weeks.

Cohorts of 3-6 patients receive escalating doses of gemcitabine 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.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Gynecologic Oncology Group

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

  • Previously untreated disease
  • Any cell type
  • Stage IB_2, IIA, IIB, IIIA, IIIB, or IVA
• Para-aortic lymph nodes negative by radiologic evaluation or by biopsy if CT scan is suspicious for adenopathy
• No known metastases to scalene nodes or other organs outside the radiotherapy field
• Study enrollment within 8 weeks of diagnosis
• Performance status - GOG 0-2
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times normal
• SGOT no greater than 3 times normal
• Creatinine less than 2.0 mg/dL
• No renal abnormalities (e.g., pelvic kidney, horseshoe kidney, or renal transplantation) that would require modification of radiotherapy fields
• No ureteral obstruction allowed unless treated with stent or nephrostomy tube
• Not pregnant
• Fertile patients must use effective contraception
• No septicemia or severe infection
• No circumstance that would preclude study completion or follow-up
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No prior cytotoxic chemotherapy
• No prior pelvic or abdominal radiotherapy
• 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; Patients receive gemcitabine IV over 30 minutes and cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36 in the absence of disease progression or unacceptable toxicity. Patients also undergo external whole pelvis radiotherapy once daily on days 1-5, 8-13, 15-20, 22-27, and 29-34. After completion of external beam radiotherapy, patients undergo intracavitary radiotherapy and parametrial radiotherapy. The total elapsed time for completion of all radiotherapy is not more than 8 weeks.

Drug: Cisplatin; Given IV; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdCyd; dFdC; Radiation: Internal Radiation Therapy; Undergo brachytherapy; Other Names: Internal Radiation; Internal Radiation Brachytherapy; Radiation Brachytherapy; Brachytherapy; Radiation: Radiation Therapy; Undergo whole pelvis radiotherapy; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of acute toxicity using the 21 major categories of the CTEP CTC version 2.0	Up to 30 days after completion of radiation therapy
Incidence of chronic toxicity using the CTC RTOG/EORTC late radiation morbidity scoring scheme	Up to 5 years
Dose of each drug	Up to 5 years
Number of cycles received	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	Up to 5 years
Overall survival	Up to 5 years
Site (local/distant) of treatment failure	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: October 1, 2003
• Primary Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: September 10, 2003
• First Submitted That Met QC Criteria: September 10, 2003
• First Posted (Estimate): September 11, 2003

Study Record Updates

• Last Update Posted (Estimate): December 25, 2014
• Last Update Submitted That Met QC Criteria: December 23, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Neoplasms, Complex and Mixed; Uterine Cervical Neoplasms; Carcinoma; Small Cell Lung Carcinoma; Carcinoma, Adenosquamous; Carcinoma, Small Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: GOG-9912 (Other Identifier: CTEP); U10CA027469 (U.S. NIH Grant/Contract); NCI-2012-02553 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000327715