Chemotherapy and Pelvic Radiation Therapy With or Without Additional Chemotherapy in Treating Patients With High-Risk Early-Stage Cervical Cancer After Radical Hysterectomy

NCT00980954 | Completed Phase 3 Results DMC

• 4 other identifiers: RTOG-0724CDR0000654709NCI-2011-01973RTOG 0724/GOG-0724
• Study Type: interventional
• Target: 236
• Locations: 4 countries
• Sites: 125

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin, 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. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without additional chemotherapy in treating cervical cancer. PURPOSE: This randomized phase III trial is studying chemotherapy and pelvic radiation therapy to see how well they work when given with or without additional chemotherapy in treating patients with high-risk early-stage cervical cancer after radical hysterectomy.

Conditions

Cervical Cancer

Keywords

cervical adenocarcinoma; cervical adenosquamous cell carcinoma; cervical squamous cell carcinoma; stage IA cervical cancer; stage IB cervical cancer; stage IIA cervical cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (Percentage of Participants Alive Without Disease)

  Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.

  From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.

Secondary Outcomes (8)

• Overall Survival (Percentage of Participants Alive)

  From randomization to death or last follow-up. Maximum follow-up time at time of analysis was 12.8 years. The 2- and 4-year survival estimates are reported.

• Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) at 12 Months

  Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)

• Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) Diarrhea Subscore at 12 Months

  Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)

• Functional Assessment of Cancer Therapy - Cervix (FACT-Cx) Cervical Cancer Subscore at 12 Months

  Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)

• Number of Participants by Highest Grade Adverse Event Reported

  From randomization to the date of last known follow-up. Maximum follow-up time was 12.8 years.

Other Outcomes (2)

• Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity

  From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.

• Disease-free Survival (Percentage of Participants Alive Without Disease) by Race

  From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.

Study Arms (2)

Arm I: Cisplatin/Radiation Therapy

ACTIVE COMPARATOR

Standard external beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) to the pelvis once daily 5 days a week for 5-6 weeks as 45 Gy in 25 fractions or 50.4 Gy in 28 fractions (1.8 Gy/fraction). Concurrent cisplatin IV over one hour once weekly for 6 weeks as 40 mg/m\^2, maximum dose 70 mg. A brachytherapy boost following radiation therapy is optional.

Drug: cisplatin; Radiation: intensity-modulated radiation therapy; Radiation: standard external beam radiation therapy; Radiation: Optional brachytherapy boost

Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

EXPERIMENTAL

Chemoradiotherapy as in arm I, followed 4-6 weeks later by paclitaxel IV \[135 mg/m2, with maximum body surface area (BSA) of 2.0 m\^2 over 3 hours\] and carboplatin IV \[area under the curve (AUC) 5 over 30 minutes\] on day 1 of 21-day cycle for 4 cycles in the absence of disease progression or unacceptable toxicity.

Drug: carboplatin; Drug: cisplatin; Drug: paclitaxel; Radiation: intensity-modulated radiation therapy; Radiation: standard external beam radiation therapy; Radiation: Optional brachytherapy boost

Interventions

carboplatin DRUG

Intravenously

Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

cisplatin DRUG

Intravenously

Arm I: Cisplatin/Radiation Therapy; Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

paclitaxel DRUG

Intravenously

Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

intensity-modulated radiation therapy RADIATION

Daily fractions

Also known as: IMRT

Arm I: Cisplatin/Radiation Therapy; Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

standard external beam radiation therapy RADIATION

Daily fractions

Also known as: EBRT

Arm I: Cisplatin/Radiation Therapy; Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

Optional brachytherapy boost RADIATION

Low-dose rate (20-25 Gy single application) or high-dose rate (12-18 Gy 2-3 applications), dependent on external beam dose.

Arm I: Cisplatin/Radiation Therapy; Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed squamous, adenosquamous, or adenocarcinoma of the cervix with any/all of the following high-risk features after surgery: * Positive pelvic nodes * Positive parametrium * Positive para-aortic nodes that have been completely resected and are positron emission tomography (PET)/computed tomography (CT) scan-negative * PET only required if positive para-aortic nodes during surgery * Clinical stage IA2, IB, or IIA disease (this corresponds to surgical tumor node metastasis (TNM) staging of T1-T2, N1, M0) * Must have undergone radical hysterectomy (open, laparoscopically, or robotic) and staging within the past 70 days * Para-aortic and pelvic node sampling required * If the patient did not have a para-aortic lymph node sampling/dissection, but had common iliac node dissection that was negative, a PET-CT is recommended, but not required * A negative pre- or post-operative PET scan or PET-CT scan of the para-aortic nodes is required if the patient did not undergo para-aortic or common iliac nodal sampling/dissection * No gross residual disease * No neuroendocrine histology * No distant metastases PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * Absolute neutrophil count (ANC) ≥ 1,800/mm³ * Platelets ≥ 100,000/mm³ * White blood cell count (WBC) ≥ 4,000/mm³ * Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed) * Serum creatinine ≤ 1.5 mg/dL * Bilirubin ≤ 1.5 times upper limit of normal * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) normal * Alkaline phosphatase normal * Known HIV positivity allowed provided cluster of differentiation 4 (CD4) count is ≥ 350/mm³ within the past 14 days * No other invasive malignancy within the past 3 years, except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix * No severe, active co-morbidity, including any of the following: * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months * Transmural myocardial infarction within the past 6 months * Acute bacterial or fungal infection requiring IV antibiotics at the time of study entry * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry * Coagulation defects * No prior allergic reaction to carboplatin, paclitaxel, and/or cisplatin PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior systemic chemotherapy for the current cervical cancer * Prior chemotherapy for a different cancer is allowed * No prior radiotherapy to the pelvis that would result in overlap of radiotherapy fields

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• NRG Oncology: collaborator

Study Sites (125)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Providence Hospital

Mobile, Alabama, 36608, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Arizona Center for Cancer Care-Peoria

Peoria, Arizona, 85381, United States

Location

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Mercy San Juan Medical Center

Carmichael, California, 95608, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Saint Joseph Hospital - Orange

Orange, California, 92868, United States

Location

Pomona Valley Hospital Medical Center

Pomona, California, 91767, United States

Location

Mercy Cancer Center

Sacramento, California, 95816, United States

Location

Mercy General Hospital Radiation Oncology Center

Sacramento, California, 95819, United States

Location

University of California At San Diego

San Diego, California, 92103, United States

Location

Saint Helena Hospital

St. Helena, California, 94574, United States

Location

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, 80907, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

Memorial Healthcare System - Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

Jackson Memorial Hospital-Holtz Children's Hospital

Miami, Florida, 33136, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Baptist Hospital of Miami

Miami, Florida, 33176, United States

Location

Florida Hospital

Orlando, Florida, 32803, United States

Location

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31403, United States

Location

Saint Joseph's-Candler Health System

Savannah, Georgia, 31405, United States

Location

Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Saint Alphonsus Regional Medical Center

Boise, Idaho, 83706, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Saint Vincent Anderson Regional Hospital/Cancer Center

Anderson, Indiana, 46016, United States

Location

Saint Francis Hospital and Health Centers

Beech Grove, Indiana, 46107, United States

Location

Franciscan Saint Margaret Health-Hammond Campus

Hammond, Indiana, 46320, United States

Location

Franciscan Saint Francis Health-Indianapolis

Indianapolis, Indiana, 46237, United States

Location

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, 46545-1470, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Mercy Medical Center - North Iowa

Mason City, Iowa, 50401, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kansas City Cancer Centers-Southwest

Overland Park, Kansas, 66210, United States

Location

Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Central Maryland Radiation Oncology in Howard County

Columbia, Maryland, 21044, United States

Location

Holy Cross Hospital

Silver Spring, Maryland, 20910, United States

Location

Hickman Cancer Center

Adrian, Michigan, 49221, United States

Location

Saint John Hospital and Medical Center

Detroit, Michigan, 48236, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Saint Joseph Mercy Port Huron

Port Huron, Michigan, 48060, United States

Location

Saint John Macomb-Oakland Hospital

Warren, Michigan, 48093, United States

Location

Abbott-Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Kansas City Cancer Center - South

Kansas City, Missouri, 64131, United States

Location

Kansas City Cancer Centers - North

Kansas City, Missouri, 64154, United States

Location

Kansas City Cancer Center-Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

Phelps County Regional Medical Center

Rolla, Missouri, 65401, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

CoxHealth South Hospital

Springfield, Missouri, 65807, United States

Location

Saint John's Mercy Medical Center

St Louis, Missouri, 63141, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

The Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Elliot Hospital

Manchester, New Hampshire, 03103, United States

Location

Cooper Hospital University Medical Center

Camden, New Jersey, 08103, United States

Location

Morristown Memorial Hospital

Morristown, New Jersey, 07962, United States

Location

Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

Mount Holly, New Jersey, 08060, United States

Location

UMDNJ - New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

MD Anderson Cancer Center at Cooper-Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

State University of New York Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Highland Hospital

Rochester, New York, 14620, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Montefiore Medical Center-Weiler Division

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, 44304, United States

Location

Akron General Medical Center

Akron, Ohio, 44307, United States

Location

Summa Barberton Hospital

Barberton, Ohio, 44203, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Summa Health Center at Lake Medina

Medina, Ohio, 44256, United States

Location

UHHS-Chagrin Highlands Medical Center

Orange, Ohio, 44122, United States

Location

Southern Ohio Medical Center

Portsmouth, Ohio, 45662, United States

Location

Robinson Radiation Oncology

Ravenna, Ohio, 44266, United States

Location

Cancer Care Center, Incorporated

Salem, Ohio, 44460, United States

Location

Ireland Cancer Center at Firelands Regional Medical Center

Sandusky, Ohio, 44870, United States

Location

Flower Hospital

Sylvania, Ohio, 43560, United States

Location

University of Toledo

Toledo, Ohio, 43614, United States

Location

UHHS-Westlake Medical Center

Westlake, Ohio, 44145, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

Location

Delaware County Memorial Hospital

Drexel Hill, Pennsylvania, 19026, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Lankenau Hospital

Wynnewood, Pennsylvania, 19096, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Sanford Cancer Center-Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

Location

University of Tennessee - Knoxville

Knoxville, Tennessee, 37920, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Methodist Hospital

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

McKay-Dee Hospital Center

Ogden, Utah, 84403, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Dixie Medical Center Regional Cancer Center

St. George, Utah, 84770, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, 98902, United States

Location

Wheeling Hospital

Wheeling, West Virginia, 26003, United States

Location

Saint Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Aurora West Allis Medical Center

West Allis, Wisconsin, 53227, United States

Location

McGill University Department of Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Pamela Youde Nethersole Eastern Hospital

Chai Wan, Hong Kong

Location

Seoul National University Bundang Hospital

Seongnam, Kyeonggi-do, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Gangnam Severance Hospital

Seoul, 135-720, South Korea

Location

Korea Cancer Center Hospital

Seoul, 139-706, South Korea

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Carboplatin; Cisplatin; Paclitaxel; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

2155743208

Study Officials

• Anuja Jhingran, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2009
• First Posted: September 21, 2009
• Study Start: September 1, 2009
• Primary Completion: December 14, 2023
• Study Completion: September 4, 2025
• Last Updated: December 31, 2025
• Results First Posted: November 6, 2024

Record last verified: 2025-09

Locations

CA (1); US (119); HK (1); KR (4)