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

Study ID
STU 122010-065

Study Sites

  • UT Southwestern Ambulatory Services

Contact
Annette Paulsen
214/648-2290
ANNETTE.PAULSEN@UTSouthwestern.edu

Principal Investigator
David Miller, M.D.

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

Brief Overview

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.

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