Cisplatin and Radiation Therapy With or Without Hyperthermia Therapy in Treating Patients With Cervical Cancer

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Primary Purpose

Status

Terminated

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

cisplatin

hyperthermia treatment

brachytherapy

external beam radiation therapy

About this trial

This is an interventional treatment trial for Cervical Cancer focused on measuring stage IA cervical cancer, stage IB cervical cancer, stage IIA cervical cancer, stage IIB cervical cancer, stage III cervical cancer, stage IVA cervical cancer, cervical adenocarcinoma, cervical adenosquamous cell carcinoma, cervical squamous cell carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion criteria: Invasive cervical carcinoma (squamous, adeno or adenosquamous histologies, small cell histology excluded) age >18years International Federation of Gynecology and Obstetrics ((FIGO) stage IB2, IIA-IVA, FIGO stages IA, IB1 with positive pelvic lymph nodes or parametria either on imaging techniques or pathologically involved at the time of surgery. patients undergoing surgical removal of the cervix and uterus are not eligible, parametria either on imaging techniques or pathologically involved at the time • Performance status Eastern Cooperative Oncology Group(ECOG)/World Health Organisation (WHO) 0, 1 or >/=70%respectively White Blood count (WBC) ≥ 3,000, platelets ≥ 100,000, Absolute Neutrophil Count (ANC) > 1500 • serum bilirubin ≤ 1.5 times upper limit of normal, transaminase ≤ 3 times upper limit of normal calculated creatinine clearance >60milliliters (mls)/liter ( Cockcroft) OR creatinine </= 2.0mgs% paraaortic adenopathy absent or 1.5 centimeter (cm) in greatest dimension on Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) scan; No history of myocardial infarction in the last 6 months no symptomatic angina pectoris negative pregnancy test in patients under 50 Hemoglobin >12.0 Gd/dl or >7.5 mmo;/L with transfusion if needed written written informed consent Exclusion criteria: surgical resection of the primary tumor (i.e. Total abdominal hysterectomy (TAH)/ Bilateral salpingoophorectomy (BSO) patients with pacemakers or implanted defibrillators patients with significant metallic foreign bodies (i.e. hip replacements, bone metallic rods,orthopedic plates, etc.) prior radiotherapy or chemotherapy

Sites / Locations

Duke Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I

Arm II

Arm Description

Patients received cisplatin IV and concurrently underwent hyperthermia treatment over 60-90 minutes on day 1. Patients also underwent external beam radiation therapy once daily on days 1-5. Treatment repeated weekly for 5-6 weeks in the absence of disease progression or unacceptable toxicity. After completion of chemoradiotherapy and hyperthermia, patients underwent brachytherapy to the cervix for 2-3 days.

Patients received cisplatin and undergo external beam radiation therapy (and brachytherapy) as in arm I.

Outcomes

Primary Outcome Measures

Primary Tumor Response Rate at 4-6 Weeks Post Treatment

Primary tumor response rate is the proportion of subjects achieving a best response of complete (CR) or partial (PR) responses, according to the RECIST criteria for change in sum of longest diameters.

Five-year Failure-free Survival

Five-year failure free survival (FFS) time was defined as the time from randomization until relapse/disease progression (local and/or distant) or death from any cause. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The 5-year FFS rate is a percentage representing the fraction of randomized patients who, after 5 years, are disease free or alive.

Five-Year Local Recurrence-Free Survival

Five-year local recurrence-free survival (LRFS) time was defined as the time from randomization until local progressive disease or death from any cause. Local recurrence was defined as evidence of disease progression on physical exam or radiologic study, confirmed histologically by tissue biopsy. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The 5-year LRFS rate is a percentage representing the fraction of randomized patients who, after 5 years, do not have local progression or are alive.

Five-Year Overall Survival

Five-year overall survival (OS) time was time from date of randomization until death from any cause. The 5-year OS rate is a percentage, representing the fraction of randomized patients who, after 5 years, are still alive.

Secondary Outcome Measures

Full Information

NCT ID

NCT00085631

First Posted

June 10, 2004

Last Updated

July 10, 2013

Sponsor

Mark Dewhirst

Collaborators

National Cancer Institute (NCI), Northwestern University

1. Study Identification

Unique Protocol Identification Number

NCT00085631

Brief Title

Cisplatin and Radiation Therapy With or Without Hyperthermia Therapy in Treating Patients With Cervical Cancer

Official Title

An International Multi Center Phase III Study of Chemoradiotherapy Versus Chemoradiotherapy Plus Hyperthermia for Locally Advanced Cervical Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

July 2013

Overall Recruitment Status

Terminated

Why Stopped

Study was closed because of slow accrual

Study Start Date

March 2003 (undefined)

Primary Completion Date

November 2008 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mark Dewhirst

Collaborators

National Cancer Institute (NCI), Northwestern University

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. It is not yet known whether chemotherapy and radiation therapy are more effective with or without hyperthermia therapy in treating cervical cancer. PURPOSE: This randomized phase III trial compared the safety and efficacy of cisplatin and radiation therapy, together with hyperthermia therapy versus cisplatin and radiation therapy alone in the treatment of locally advanced cervical cancer.

Detailed Description

OBJECTIVES: Compare local control, failure-free survival, and overall survival of patients with locally advanced carcinoma of the cervix treated with cisplatin and radiotherapy alone, versus cisplatin and radiotherapy with hyperthermia . OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease stage (IIB or IIIA vs IIIB or IVA) and age (< 60 years vs ≥ 60 years). Patients are randomized to 1 of 2 treatment arms. LIMITATIONS: There are integrity issues with the currently available data, involving international institutions, in that several pieces of information relating to patient accrual and outcomes cannot be verified. Therefore, it would be inappropriate to report outcome measures for this study. Baseline measures of age and gender are reported for the entire study cohort. Participant flow is reported by treatment arm assignment, which was available for a majority of patients in the currently available data. Adverse events are reported for the entire cohort, as some adverse events could not be classified within a particular treatment arm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cervical Cancer

Keywords

stage IA cervical cancer, stage IB cervical cancer, stage IIA cervical cancer, stage IIB cervical cancer, stage III cervical cancer, stage IVA cervical cancer, cervical adenocarcinoma, cervical adenosquamous cell carcinoma, cervical squamous cell carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

101 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Experimental

Arm Description

Patients received cisplatin IV and concurrently underwent hyperthermia treatment over 60-90 minutes on day 1. Patients also underwent external beam radiation therapy once daily on days 1-5. Treatment repeated weekly for 5-6 weeks in the absence of disease progression or unacceptable toxicity. After completion of chemoradiotherapy and hyperthermia, patients underwent brachytherapy to the cervix for 2-3 days.

Arm Title

Arm II

Arm Type

Active Comparator

Arm Description

Patients received cisplatin and undergo external beam radiation therapy (and brachytherapy) as in arm I.

Intervention Type

Drug

Intervention Name(s)

cisplatin

Other Intervention Name(s)

Platinol-AQ

Intervention Description

Given IV

Intervention Type

Procedure

Intervention Name(s)

hyperthermia treatment

Intervention Description

Patients undergo hyperthermia treatment over 60-90 minutes

Intervention Type

Radiation

Intervention Name(s)

brachytherapy

Intervention Description

Patients undergo brachytherapy for 2-3 days

Intervention Type

Radiation

Intervention Name(s)

external beam radiation therapy

Intervention Description

Patients undergo external beam radiation therapy once daily on days 1-5

Primary Outcome Measure Information:

Title

Primary Tumor Response Rate at 4-6 Weeks Post Treatment

Description

Primary tumor response rate is the proportion of subjects achieving a best response of complete (CR) or partial (PR) responses, according to the RECIST criteria for change in sum of longest diameters.

Time Frame

3 months from start of therapy

Title

Five-year Failure-free Survival

Description

Five-year failure free survival (FFS) time was defined as the time from randomization until relapse/disease progression (local and/or distant) or death from any cause. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The 5-year FFS rate is a percentage representing the fraction of randomized patients who, after 5 years, are disease free or alive.

Time Frame

5 Years

Title

Five-Year Local Recurrence-Free Survival

Description

Five-year local recurrence-free survival (LRFS) time was defined as the time from randomization until local progressive disease or death from any cause. Local recurrence was defined as evidence of disease progression on physical exam or radiologic study, confirmed histologically by tissue biopsy. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The 5-year LRFS rate is a percentage representing the fraction of randomized patients who, after 5 years, do not have local progression or are alive.

Time Frame

5 years

Title

Five-Year Overall Survival

Description

Five-year overall survival (OS) time was time from date of randomization until death from any cause. The 5-year OS rate is a percentage, representing the fraction of randomized patients who, after 5 years, are still alive.

Time Frame

5 Years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion criteria: Invasive cervical carcinoma (squamous, adeno or adenosquamous histologies, small cell histology excluded) age >18years International Federation of Gynecology and Obstetrics ((FIGO) stage IB2, IIA-IVA, FIGO stages IA, IB1 with positive pelvic lymph nodes or parametria either on imaging techniques or pathologically involved at the time of surgery. patients undergoing surgical removal of the cervix and uterus are not eligible, parametria either on imaging techniques or pathologically involved at the time • Performance status Eastern Cooperative Oncology Group(ECOG)/World Health Organisation (WHO) 0, 1 or >/=70%respectively White Blood count (WBC) ≥ 3,000, platelets ≥ 100,000, Absolute Neutrophil Count (ANC) > 1500 • serum bilirubin ≤ 1.5 times upper limit of normal, transaminase ≤ 3 times upper limit of normal calculated creatinine clearance >60milliliters (mls)/liter ( Cockcroft) OR creatinine </= 2.0mgs% paraaortic adenopathy absent or 1.5 centimeter (cm) in greatest dimension on Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) scan; No history of myocardial infarction in the last 6 months no symptomatic angina pectoris negative pregnancy test in patients under 50 Hemoglobin >12.0 Gd/dl or >7.5 mmo;/L with transfusion if needed written written informed consent Exclusion criteria: surgical resection of the primary tumor (i.e. Total abdominal hysterectomy (TAH)/ Bilateral salpingoophorectomy (BSO) patients with pacemakers or implanted defibrillators patients with significant metallic foreign bodies (i.e. hip replacements, bone metallic rods,orthopedic plates, etc.) prior radiotherapy or chemotherapy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ellen L. Jones, MD, PhD

Organizational Affiliation

Duke Cancer Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Leonard R. Prosnitz, MD

Organizational Affiliation

Duke Cancer Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Mark Dewhirst, DVM PhD

Organizational Affiliation

Duke Cancer Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Zeljko Vujaskovic, MD PhD

Organizational Affiliation

Duke Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Duke Cancer Institute

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Cervical Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial