Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00980954
Recruitment Status : Recruiting
First Posted : September 21, 2009
Last Update Posted : March 21, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Tracking Information
First Submitted Date  ICMJE September 18, 2009
First Posted Date  ICMJE September 21, 2009
Last Update Posted Date March 21, 2019
Study Start Date  ICMJE September 2009
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2013)
Disease-free survival [ 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. ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2009)
Disease-free survival
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2013)
  • Overall survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years. ]
  • Chemotherapy-induced neuropathy as measured by FACT-GOG/NTX4 [ Time Frame: From completion of concurrent chemoradiation to 12 months. ]
  • Quality of life as measured by FACT-Cx and FACIT-D [ Time Frame: From completion of concurrent chemoradiation to 12 months. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2009)
  • Adverse events
  • Overall survival
  • Chemotherapy-induced neuropathy as measured by FACT-GOG/NTX4
  • Quality of life as measured by FACT-Cx and FACIT-D
  • Associations between tumor molecular signatures from fixed tissue samples and outcomes, such as adverse events, disease-free survival, and overall survival
  • Associations between secreted factors from serum and plasma samples and adverse events or outcome
  • Associations between SNPs in genes from buffy coat and a genetic predisposition to tumor formation itself or a response to cytotoxic therapy
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cervical Cancer
Intervention  ICMJE
  • Drug: carboplatin
    Given IV
  • Drug: cisplatin
    Given IV
  • Drug: paclitaxel
    Given IV
Study Arms  ICMJE
  • Experimental: Arm I: Cisplatin/Radiation Therapy
    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.
    Intervention: Drug: cisplatin
  • Experimental: Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel
    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.
    Interventions:
    • Drug: carboplatin
    • Drug: cisplatin
    • Drug: paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 18, 2009)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2026
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Canada,   Hong Kong,   Korea, Republic of,   United States
Removed Location Countries China
 
Administrative Information
NCT Number  ICMJE NCT00980954
Other Study ID Numbers  ICMJE RTOG-0724
CDR0000654709
NCI-2011-01973 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RTOG 0724/GOG-0724 ( Other Identifier: NRG Oncology )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Radiation Therapy Oncology Group
Study Sponsor  ICMJE Radiation Therapy Oncology Group
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • NRG Oncology
Investigators  ICMJE
Principal Investigator: Anuja Jhingran, MD M.D. Anderson Cancer Center
PRS Account Radiation Therapy Oncology Group
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP