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

February 6, 2006
November 6, 2012
February 2005
December 2009   (final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00287911 on ClinicalTrials.gov Archive Site
Not Provided
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Topotecan, Cisplatin, and Radiation Therapy in Treating Patients With Advanced Cervical Cancer
A Phase I Study of Adjuvant Topotecan and Cisplatin With Concurrent Radiation Therapy for Advanced Cervical Cancer

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Cervical Cancer
  • 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
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.

Interventions:
  • Drug: cisplatin
  • Drug: topotecan hydrochloride
  • Radiation: brachytherapy
  • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
December 2009
December 2009   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00287911
CDR0000452043, UMN-2001LS041, UMN-WCC-34, 104864/638
Yes
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
GlaxoSmithKline
Study Chair: Linda F. Carson, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP