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
18 Years
N/A
Female
Cervical Cancer
Trial Information
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
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.
Inclusion 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 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Disease-free survival
Outcome Time Frame:
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.
Safety Issue:
No
Principal Investigator
Anuja Jhingran, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Federal Government
Study ID:
RTOG 0724
NCT ID:
NCT00980954
Start Date:
September 2009
Completion Date:
Related Keywords:
- Cervical Cancer
- cervical adenocarcinoma
- cervical adenosquamous cell carcinoma
- cervical squamous cell carcinoma
- stage IA cervical cancer
- stage IB cervical cancer
- stage IIA cervical cancer
- Uterine Cervical Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Penrose Cancer Center at Penrose Hospital | Colorado Springs, Colorado 80933 |
| West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
| Case Comprehensive Cancer Center | Cleveland, Ohio 44106-5065 |
| Natalie Warren Bryant Cancer Center at St. Francis Hospital | Tulsa, Oklahoma 74136 |
| Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
| Medical College of Wisconsin Cancer Center | Milwaukee, Wisconsin 53226 |
| Rapid City Regional Hospital | Rapid City, South Dakota 57709 |
| St. Joseph's Hospital and Medical Center | Phoenix, Arizona 85001-2071 |
| Rush University Medical Center | Chicago, Illinois 60612-3824 |
| Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
| Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center | Milwaukee, Wisconsin 53201-2901 |
| Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
| Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
| Northside Hospital Cancer Center | Atlanta, Georgia 30342-1611 |
| Hulston Cancer Center at Cox Medical Center South | Springfield, Missouri 65807 |
| St. John's Regional Health Center | Springfield, Missouri 65804 |
| Carol G. Simon Cancer Center at Morristown Memorial Hospital | Morristown, New Jersey 07962 |
| UMDNJ University Hospital | Newark, New Jersey 07103 |
| SUNY Downstate Medical Center | Brooklyn, New York 11203 |
| McDowell Cancer Center at Akron General Medical Center | Akron, Ohio 44307 |
| Women and Infants Hospital of Rhode Island | Providence, Rhode Island 02905 |
| Baptist-South Miami Regional Cancer Program | Miami, Florida 33176 |
| Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
| Albert Einstein Cancer Center at Albert Einstein College of Medicine | Bronx, New York 10461 |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
| St. Vincent Hospital Regional Cancer Center | Green Bay, Wisconsin 54307-3508 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| David C. Pratt Cancer Center at St. John's Mercy | St. Louis, Missouri 63141 |
| Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore, Maryland 21201 |
| University of Mississippi Cancer Clinic | Jackson, Mississippi 39216-4505 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
| M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
| Methodist Estabrook Cancer Center | Omaha, Nebraska 68114-4199 |
| Huntsman Cancer Institute at University of Utah | Salt Lake City, Utah 84112 |
| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago, Illinois 60611 |
| Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton | Marlton, New Jersey 08053 |
| Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center | Boise, Idaho 83706 |
| OSF St. Francis Medical Center | Peoria, Illinois 61637 |
| Hickman Cancer Center at Bixby Medical Center | Adrian, Michigan 49221 |
| Cancer Institute of New Jersey at Cooper - Voorhees | Voorhees, New Jersey 08043 |
| Highland Hospital of Rochester | Rochester, New York 14620 |
| Providence Cancer Center at Providence Portland Medical Center | Portland, Oregon 97213-2967 |
| Providence St. Vincent Medical Center | Portland, Oregon 97225 |
| Dixie Regional Medical Center - East Campus | Saint George, Utah 84770 |
| Mercy Cancer Center at Mercy Medical Center - North Iowa | Mason City, Iowa 50401 |
| Cancer Treatment Center | Wooster, Ohio 44691 |
| University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami, Florida 33136 |
| Michiana Hematology-Oncology, PC - South Bend | Mishawaka, Indiana 46545-1470 |
| Greater Baltimore Medical Center Cancer Center | Baltimore, Maryland 21204 |
| Mercy Regional Cancer Center at Mercy Hospital | Port Huron, Michigan 48060 |
| Summa Center for Cancer Care at Akron City Hospital | Akron, Ohio 44309-2090 |
| Barberton Citizens Hospital | Barberton, Ohio 44203 |
| Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus, Ohio 43210-1240 |
| Flower Hospital Cancer Center | Sylvania, Ohio 43560 |
| McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center | Reading, Pennsylvania 19612-6052 |
| Jon and Karen Huntsman Cancer Center at Intermountain Medical Center | Murray, Utah 84157 |
| Val and Ann Browning Cancer Center at McKay-Dee Hospital Center | Ogden, Utah 84403 |
| Schiffler Cancer Center at Wheeling Hospital | Wheeling, West Virginia 26003 |
| Seattle Cancer Care Alliance | Seattle, Washington 98109 |
| St. Joseph Hospital Regional Cancer Center - Orange | Orange, California 92868-3849 |
| Radiological Associates of Sacramento Medical Group, Incorporated | Sacramento, California 95815 |
| Queen's Cancer Institute at Queen's Medical Center | Honolulu, Hawaii 96813 |
| Elliot Regional Cancer Center at Elliot Hospital | Manchester, New Hampshire 03103 |
| Mercy General Hospital | Sacramento, California 95819 |
| Cancer Care Center, Incorporated | Salem, Ohio 44460 |
| Saint John's Cancer Center at Saint John's Medical Center | Anderson, Indiana 46016 |
| UHHS Chagrin Highlands Medical Center | Orange Villager, Ohio 44122 |
| Saint Helena Hospital | Saint Helena, California 94574 |
| Arizona Center for Cancer Care - Peoria | Peoria, Arizona 85381 |
| Nebraska Medical Center | Omaha, Nebraska 68198 |
| Robinson Radiation Oncology | Ravenna, Ohio 44266 |
