Chemotherapy and Pelvic Radiation Therapy With or Without Additional Chemotherapy in Treating Patients With High-Risk Early-Stage Cervical Cancer After Radical Hysterectomy
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Cervical Cancer |
Drug: carboplatin Drug: cisplatin Drug: paclitaxel |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Primary Purpose: Treatment |
| 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 |
- Disease-free survival [ Designated as safety issue: No ]
- Adverse events [ Designated as safety issue: Yes ]
- Overall survival [ Designated as safety issue: No ]
- Chemotherapy-induced neuropathy as measured by FACT-GOG/NTX4 [ Designated as safety issue: No ]
- Quality of life as measured by FACT-Cx and FACIT-D [ Designated as safety issue: No ]
- Associations between tumor molecular signatures from fixed tissue samples and outcomes, such as adverse events, disease-free survival, and overall survival [ Designated as safety issue: No ]
- Associations between secreted factors from serum and plasma samples and adverse events or outcome [ Designated as safety issue: No ]
- Associations between SNPs in genes from buffy coat and a genetic predisposition to tumor formation itself or a response to cytotoxic therapy [ Designated as safety issue: No ]
| Estimated Enrollment: | 400 |
| Study Start Date: | September 2009 |
| Estimated Primary Completion Date: | August 2021 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Drug: cisplatin
Given IV
|
|
Experimental: 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.
|
Drug: carboplatin
Given IV
Drug: cisplatin
Given IV
Drug: paclitaxel
Given IV
|
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 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 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 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 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| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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 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
- ANC ≥ 1,800/mm³
- Platelets ≥ 100,000/mm³
- 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
- ALT and/or AST normal
- Alkaline phosphatase normal
- Known HIV positivity allowed provided 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
Contacts and Locations
Show 76 Study Locations| Principal Investigator: | Anuja Jhingran, MD | M.D. Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | Walter John Curran, Jr, Radiation Therapy Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00980954 History of Changes |
| Other Study ID Numbers: | CDR0000654709, RTOG-0724 |
| Study First Received: | September 18, 2009 |
| Last Updated: | September 16, 2012 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
cervical adenocarcinoma cervical adenosquamous cell carcinoma cervical squamous cell carcinoma |
stage IA cervical cancer stage IB cervical cancer stage IIA cervical cancer |
Additional relevant MeSH terms:
|
Uterine Cervical Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Neoplasms Uterine Cervical Diseases Uterine Diseases Genital Diseases, Female Cisplatin Carboplatin |
Paclitaxel Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic |
ClinicalTrials.gov processed this record on May 21, 2013