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
The purpose of this study is to compare the effects, good and/or bad, of giving additional chemotherapy to you after the usual treatment of chemotherapy and radiation for your cervical cancer. The standard treatment for your type of cervical cancer is cisplatin chemotherapy plus radiation. The study will determine whether adding chemotherapy with carboplatin and paclitaxel (experimental for your type of cervical cancer) to standard radiation and cisplatin chemotherapy improves survival without increasing side effects.
Disease Group: Cervix
Treatment Agent: Carboplatin,Cisplatin,Paclitaxel,Radiation
Treatment Location: Both at MD Anderson & Other Sites
Sponsor: NRG Oncology (NRG)
To determine if adjuvant systemic chemotherapy following chemoradiation therapy will improve disease-free survival compared to chemoradiation therapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after a radical hysterectomy. Secondary Objectives: To evaluate adverse events Overall survival Quality of life Chemotherapy-induced neuropathy To perform a post-hoc dose-volume evaluation between cases treated with standard radiation therapy (RT) and cases treated with Intensity-Modulated Radiation Therapy (IMRT) with respect to toxicity and local control To collect fixed tissue 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 to: Identify secreted factors from serum and plasma that may be associated with adverse events or outcome 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
IRB Review and Approval Date: 10/06/2010
Recruitment Status: Open
Projected Accrual: 30
1) Patients must have undergone radical hysterectomy (open,
laparoscopically or robotic) and staging including pelvic node sampling
or dissection for cervical carcinoma within 70 days prior to study
entry. [NOTE: 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
2) Patients with clinical stage IA2, IB or IIA squamous, adenosquamous, or adenocarcinoma of the cervix who have any/all of the following high-risk features after surgery: Positive pelvic nodes, Positive parametrium, Positive para-aortic nodes-completely resected, Positron Emission Tomography/Computerized Tomography (PET/CT) negative (PET only required if positive para-aortic nodes during surgery)
3) No distant metastases, based upon the following minimum diagnostic workup [NOTE: Patients with positive para-aortic nodes- completely resected, PET/CT negative are eligible]: A. History/physical examination within 56 days prior to study entry; B. Contrast-enhanced imaging of the abdomen and pelvis by either CT, Magnetic Resonance Imaging (MRI), or PET-CT (whole body) within 90 days prior to registration. (NOTE: whole body PET-CT is preferred); C. Chest x-ray (PA and lateral) or chest CT within 70 days prior to study entry (except for those who have had whole body PET-CT).
4) Zubrod performance status 0-1.
5) Age of greater than or equal to 18
6) Complete Blood Count (CBC)/differential obtained 14 days prior to study entry, with adequate bone marrow function defined as follows: A. Absolute neutrophil count (ANC) greater than or equal to 1,800 cells/mm^3; B. Platelets greater than or equal to 100,000 cells/mm^3; C. Hemoglobin greater than or equal to 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb greater than or equal to 10.0 g/dl is acceptable.); D. White blood cell count greater than or equal to 4000 cells/mm^3.
7) Adequate hepatic and renal function defined as follows: 1 Serum creatinine less than or equal to 1.5 mg/dL, 2 Bilirubin less than or equal to 1.5 times normal, 3 Alkaline phosphatase within upper limits of institutional normal, 4 ALT/SGPT and/or AST/SGOT within upper limits of institutional normal, 5 Patients with known HIV positive must have a CD4 cell count be greater than or equal to 350 cells/mm^3. All within 14 days prior to study entry (note, however, that HIV testing is not required for entry into this protocol.)
8) Patient must provide study-specific informed consent prior to study entry.
1) Prior invasive malignancy (except non-melanomatous skin cancer)
unless disease free for a minimum of 3 years (For example, carcinoma in
situ of the breast, oral cavity, or cervix are all permissible).
2) Patients can not have any neuroendocrine histology in pathology.
3) Prior systemic chemotherapy for the current cervical cancer; note that prior chemotherapy for a different cancer is allowable.
4) Prior radiation therapy to the pelvis that would result in overlap of radiation therapy fields.
5) Severe, active co-morbidity, defined as follows: A. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; B. Transmural myocardial infarction within the last 6 months; C. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry; D. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry; E. Coagulation defects; note, however, that coagulation parameters are not required for entry into this protocol.
6) Prior allergic reaction to carboplatin, paclitaxel, and/or cisplatin.
7) Patients who have gross residual disease or distant metastatic disease.
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