Clinical trial NCT00980954: Chemotherapy and Pelvic Radiation Therapy With or Without Additional Chemotherapy in Treating Patients With High-Risk Early-Stage Cervical Cancer After Radical Hysterectomy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2009-09-21
Enrollment: 236
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease-free Survival (Percentage of Participants Alive Without Disease)
timeFrame: 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:
measure: Overall Survival (Percentage of Participants Alive)
timeFrame: 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.
measure: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) at 12 Months
timeFrame: Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
measure: Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) Diarrhea Subscore at 12 Months
timeFrame: Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
measure: Functional Assessment of Cancer Therapy - Cervix (FACT-Cx) Cervical Cancer Subscore at 12 Months
timeFrame: Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
measure: Number of Participants by Highest Grade Adverse Event Reported
timeFrame: From randomization to the date of last known follow-up. Maximum follow-up time was 12.8 years.
measure: Associations Between Tumor Molecular Signatures, From Fixed Tissue, and Outcomes Such as Adverse Events, Disease Free Survival and Overall Survival
timeFrame: From randomization to last follow-up
measure: Associations Between Secreted Factors From Serum and Plasma With Adverse Events or Outcome
timeFrame: From randomization to last follow-up.
measure: Associations Between Single Nucleotide Polymorphisms (SNPs) in Genes From Buffy Coat and a Genetic Predisposition to Tumor Formation Itself or a Response to Cytotoxic Therapy
timeFrame: From randomization to last follow-up.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: Providence Hospital
state: Alabama
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Peoria
country: United States
facility: Arizona Center for Cancer Care-Peoria
state: Arizona
city: Phoenix
country: United States
facility: Saint Joseph's Hospital and Medical Center
state: Arizona
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: Carmichael
country: United States
facility: Mercy San Juan Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Orange
country: United States
facility: Saint Joseph Hospital - Orange
state: California
city: Pomona
country: United States
facility: Pomona Valley Hospital Medical Center
state: California
city: Sacramento
country: United States
facility: Mercy Cancer Center
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital Radiation Oncology Center
state: California
city: Saint Helena
country: United States
facility: Saint Helena Hospital
state: California
city: San Diego
country: United States
facility: University of California At San Diego
state: California
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Deerfield Beach
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System - Joe DiMaggio Children's Hospital
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital-Holtz Children's Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Savannah
country: United States
facility: Saint Joseph's-Candler Health System
state: Georgia
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Boise
country: United States
facility: Saint Alphonsus Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Anderson
country: United States
facility: Saint Vincent Anderson Regional Hospital/Cancer Center
state: Indiana
city: Beech Grove
country: United States
facility: Saint Francis Hospital and Health Centers
state: Indiana
city: Hammond
country: United States
facility: Franciscan Saint Margaret Health-Hammond Campus
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan Saint Francis Health-Indianapolis
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology Oncology PC-Mishawaka
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Mason City
country: United States
facility: Mercy Medical Center - North Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Kansas City Cancer Centers-Southwest
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Columbia
country: United States
facility: Central Maryland Radiation Oncology in Howard County
state: Maryland
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Adrian
country: United States
facility: Hickman Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Port Huron
country: United States
facility: Saint Joseph Mercy Port Huron
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Cancer Center - South
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - North
state: Missouri
city: Lee's Summit
country: United States
facility: Kansas City Cancer Center-Lee's Summit
state: Missouri
city: Rolla
country: United States
facility: Phelps County Regional Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint John's Mercy Medical Center
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Omaha
country: United States
facility: The Nebraska Medical Center
state: Nebraska
city: Manchester
country: United States
facility: Elliot Hospital
state: New Hampshire
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Mount Holly
country: United States
facility: Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
state: New Jersey
city: Newark
country: United States
facility: UMDNJ - New Jersey Medical School
state: New Jersey
city: Voorhees
country: United States
facility: MD Anderson Cancer Center at Cooper-Voorhees
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center-Weiler Division
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: State University of New York Downstate Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: Highland Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: Summa Akron City Hospital/Cooper Cancer Center
state: Ohio
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Barberton
country: United States
facility: Summa Barberton Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
city: Medina
country: United States
facility: Summa Health Center at Lake Medina
state: Ohio
city: Orange Village
country: United States
facility: UHHS-Chagrin Highlands Medical Center
state: Ohio
city: Portsmouth
country: United States
facility: Southern Ohio Medical Center
state: Ohio
city: Ravenna
country: United States
facility: Robinson Radiation Oncology
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: Sandusky
country: United States
facility: Ireland Cancer Center at Firelands Regional Medical Center
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Westlake
country: United States
facility: UHHS-Westlake Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center-Oncology Clinic
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee - Knoxville
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Saint George
country: United States
facility: Dixie Medical Center Regional Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Wheeling
country: United States
facility: Wheeling Hospital
state: West Virginia
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: West Allis
country: United States
facility: Aurora West Allis Medical Center
state: Wisconsin
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Seongnam City
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Kyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea Cancer Center Hospital
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Anuja Jhingran, MD
role: PRINCIPAL_INVESTIGATOR
References: