Topotecan, Cisplatin, and Radiation Therapy in Treating Patients With Advanced Cervical Cancer

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00287911
First received: February 6, 2006
Last updated: November 6, 2012
Last verified: November 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as topotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Topotecan and cisplatin may make tumor cells more sensitive to radiation therapy. Giving topotecan and cisplatin together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of topotecan when given together with cisplatin and radiation therapy in treating patients with advanced cervical cancer.


Condition Intervention Phase
Cervical Cancer
Drug: cisplatin
Drug: topotecan hydrochloride
Radiation: brachytherapy
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Adjuvant Topotecan and Cisplatin With Concurrent Radiation Therapy for Advanced Cervical Cancer

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Maximum tolerated dose of topotecan [ Time Frame: Week 3 After First Course of Therapy ] [ Designated as safety issue: Yes ]
    Adequate Response Trial Minimum length of trial to evaluate response is defined as receiving the first course of chemotherapy and living at least three weeks for repeat measurement to be performed.


Enrollment: 18
Study Start Date: February 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combo Chemotherapy and Radiation

Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Some patients may also undergo brachytherapy. Patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36 and topotecan IV continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Treatment continues 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 preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Drug: cisplatin
intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36
Other Names:
  • cisplatinum
  • CDDP
  • Platinol AQ
Drug: topotecan hydrochloride
intravenously continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36 -Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined
Other Name: Hycamtin
Radiation: brachytherapy
Some patients may also undergo brachytherapy
Radiation: radiation therapy
once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36
Other Name: radiation

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of topotecan when administered with cisplatin in patients with advanced cervical cancer.
  • Identify any unique toxicities associated with administering radiotherapy along with adjuvant cisplatin and topotecan in patients with cervical cancer.
  • Determine the feasibility of administering continuous infusion topotecan chemotherapy together with radiation therapy.
  • Assess the quality of life of patients treated with this regimen.

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

Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Some patients may also undergo brachytherapy. Patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36 and topotecan IV continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Treatment continues 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 preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Quality of life is assessed at baseline and at 4 and 14 weeks after completion of study treatment.

After completion of study treatment, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed cervical carcinoma

    • Deemed not curable by surgery or radiotherapy alone
    • The following stages are eligible:

      • Stage IIB
      • Stage IIIA or IIIB
      • Stage IVA
      • Stage IB or IIA with ≥ 1 of the following risk factors:

        • Primary tumor ≥ 6 cm
        • Positive pelvic and/or para-aortic lymph nodes (resected or unresected)
        • Positive surgical margins
        • Depth of invasion > 50% and positive capillary-lymphatic space involvement
  • The following histologic subtypes are eligible:

    • Squamous
    • Adenosquamous
    • Adenocarcinoma
  • No recurrent cervical cancer
  • Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
  • White blood cells (WBC) ≥ 3,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Granulocyte count ≥ 1,500/mm^3
  • Creatinine ≤ 2.0 mg/dL
  • Bilirubin ≤ 1.5 times institutional normal
  • Serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase ≤ 3 times institutional normal
  • No other prior or concurrent malignancies other than skin (excluding melanoma)
  • No septicemia, severe infection, gastrointestinal bleeding, or intestinal obstruction
  • No anatomic abnormalities (e.g., pelvic kidney or renal transplant) requiring modification of radiation fields
  • Fertile patients must use effective contraception
  • Negative pregnancy test
  • Patients with evidence of abnormal cardiac conduction (e.g., bundle branch block, heart block) are eligible if disease is stable for the past 6 months
  • Recovered from recent surgery

Exclusion Criteria:

  • Prior pelvic radiation
  • Pregnant or nursing
  • History of thrombus
  • History of unstable angina or myocardial infarction within the past 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00287911

Locations
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
GlaxoSmithKline
Investigators
Study Chair: Linda F. Carson, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00287911     History of Changes
Other Study ID Numbers: CDR0000452043, UMN-2001LS041, UMN-WCC-34, 104864/638
Study First Received: February 6, 2006
Last Updated: November 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
cervical squamous cell carcinoma
stage IB cervical cancer
stage IIA cervical cancer
stage IIB cervical cancer
stage III cervical cancer
stage IVA cervical cancer

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Cisplatin
Topotecan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014