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

Cervical Cancer Clinical Trial

Official title:

Phase III Randomized Study of Concurrent Chemotherapy and Pelvic Radiation Therapy With or Without Adjuvant Chemotherapy in High-Risk Patients With Early-Stage Cervical Carcinoma Following Radical Hysterectomy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00980954
• Other study ID #: RTOG-0724
• Secondary ID: CDR0000654709NCI
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 2009
• Est. completion date: August 31, 2028

Study information

• Verified date: February 2024
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

Primary

• To determine if administering adjuvant systemic chemotherapy after chemoradiotherapy will improve disease-free survival compared to chemoradiotherapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after radical hysterectomy.

Secondary

• To evaluate adverse events.

• To evaluate overall survival.

• To evaluate quality of life.

• To evaluate chemotherapy-induced neuropathy.

• To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy (IMRT) with respect to toxicity and local control.

• To collect fixed tissue samples to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival.

• To collect blood samples to identify secreted factors from serum and plasma that may be associated with adverse events or outcome and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to planned use of brachytherapy (no vs. yes), radiotherapy modality - [standard external beam radiotherapy (EBRT) vs. intensity-modulated radiotherapy (IMRT)], and radiotherapy dose (45 Gy vs. 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.

NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy.

• Arm II: Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed by the Functional Assessment of Cancer Therapy - Gynecologic Oncology Group (FACT-GOG/NTX4), FACT-Cx, and FACIT-D questionnaires at baseline; at the completion of chemoradiotherapy; and then at 6, 12, and 24 months after completion of chemoradiotherapy.

Blood and tissue samples may be collected for gene expression analysis by immuno-histochemistry (IHC) and for biomarker and polymorphism studies.

After completion of study treatment, patients are followed up very 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 238
• Est. completion date: August 31, 2028
• Est. primary completion date: December 14, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 PET/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

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• carboplatin
Given IV
• cisplatin
Given IV
• paclitaxel
Given IV

Locations

Country	Name	City	State
Canada	McGill University Department of Oncology	Montreal	Quebec
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam City	Kyeonggi-do
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea Cancer Center Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
United States	Hickman Cancer Center	Adrian	Michigan
United States	Akron General Medical Center	Akron	Ohio
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana
United States	Grady Health System	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Saint Francis Hospital and Health Centers	Beech Grove	Indiana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Montefiore Medical Center	Bronx	New York
United States	Montefiore Medical Center-Weiler Division	Bronx	New York
United States	State University of New York Downstate Medical Center	Brooklyn	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Medical Center	Duarte	California
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Franciscan Saint Margaret Health-Hammond Campus	Hammond	Indiana
United States	Hartford Hospital	Hartford	Connecticut
United States	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Queen's Medical Center	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kansas City Cancer Center - South	Kansas City	Missouri
United States	Kansas City Cancer Centers - North	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Kansas City Cancer Center-Lee's Summit	Lee's Summit	Missouri
United States	Elliot Hospital	Manchester	New Hampshire
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Summa Health Center at Lake Medina	Medina	Ohio
United States	Baptist Hospital of Miami	Miami	Florida
United States	Jackson Memorial Hospital-Holtz Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Providence Hospital	Mobile	Alabama
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	UMDNJ - New Jersey Medical School	Newark	New Jersey
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	The Nebraska Medical Center	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	UHHS-Chagrin Highlands Medical Center	Orange Village	Ohio
United States	Florida Hospital	Orlando	Florida
United States	Kansas City Cancer Centers-Southwest	Overland Park	Kansas
United States	Arizona Center for Cancer Care-Peoria	Peoria	Arizona
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Pomona Valley Hospital Medical Center	Pomona	California
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Robinson Radiation Oncology	Ravenna	Ohio
United States	Highland Hospital	Rochester	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Phelps County Regional Medical Center	Rolla	Missouri
United States	Mercy Cancer Center	Sacramento	California
United States	Mercy General Hospital Radiation Oncology Center	Sacramento	California
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Saint Helena Hospital	Saint Helena	California
United States	Saint John's Mercy Medical Center	Saint Louis	Missouri
United States	Cancer Care Center, Incorporated	Salem	Ohio
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of California At San Diego	San Diego	California
United States	Ireland Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Saint Joseph's-Candler Health System	Savannah	Georgia
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Flower Hospital	Sylvania	Ohio
United States	University of Toledo	Toledo	Ohio
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Reading Hospital	West Reading	Pennsylvania
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Wheeling Hospital	Wheeling	West Virginia
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Treatment Center	Wooster	Ohio
United States	Lankenau Hospital	Wynnewood	Pennsylvania
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival		From randomization to date of first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Analysis occurs after 43 disease-free survival failure events on Cisplatin/RT Arm.
Secondary	Overall survival		From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.
Secondary	Chemotherapy-induced neuropathy as measured by FACT-GOG/NTX4		From completion of concurrent chemoradiation to 12 months.
Secondary	Quality of life as measured by FACT-Cx and FACIT-D		From completion of concurrent chemoradiation to 12 months.