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

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Completed

CT.gov ID

NCT00287911

Collaborator

GlaxoSmithKline (Industry)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Cervical Cancer	Drug: cisplatin Drug: topotecan hydrochloride Radiation: brachytherapy Radiation: radiation therapy	Phase 1

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.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Adjuvant Topotecan and Cisplatin With Concurrent Radiation Therapy for Advanced Cervical Cancer

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: radiation

Arm

Intervention/Treatment

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 Names:

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 Names:

radiation

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of topotecan [Week 3 After First Course of Therapy]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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