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
Trial record 1 of 1 for:    Alliance A221505
Previous Study | Return to List | Next Study

Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

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: NCT03414970
Recruitment Status : Recruiting
First Posted : January 30, 2018
Last Update Posted : June 4, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Canadian Cancer Trials Group
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE January 17, 2018
First Posted Date  ICMJE January 30, 2018
Last Update Posted Date June 4, 2020
Actual Study Start Date  ICMJE February 1, 2018
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2018)
Rate of breast reconstruction complications [ Time Frame: At 24 months ]
Will be tested using a two-sample test of proportions. The test statistic will be calculated and interim analysis for futility will be performed. The primary analyses will be an intent-to-treat analysis where all patients randomized will be included in the analysis and will be analyzed based on the arm they were randomized to regardless of actual radiation schedule received. Due to the random treatment assignment with stratification for the timing of reconstruction and type of reconstruction, it is expected that the baseline patient characteristics, including the planned reconstruction procedures, are roughly balanced across the two treatment arms. A sensitivity analysis stratified by timing and type of reconstruction surgery will be conducted.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2018)
  • Incidence of acute and late radiation complications based on Common Terminology Criteria for Adverse Events 4.0 toxicity [ Time Frame: Up to 5 years ]
    The proportion of patients with acute or late radiation complications, will be estimated separately by treatment arm and will be compared across the two arms using two-sample test of proportions (Z test) with a two-sided alternative.
  • Local and local regional recurrence [ Time Frame: Up to 5 years ]
    The cumulative incidence of local and local regional recurrence will be estimated separately by treatment arm using the cumulative incidence function treating death as the competing risk and will be compared using Gray's test.
  • Local and local regional recurrence-free survival [ Time Frame: Up to 5 years ]
    Local and local regional recurrence free survival will be summarized for each arm using the Kaplan-Meier estimators, and will be compared using a log rank test.
  • Reconstruction complication rates based on reconstruction method (autologous +/- implant versus [vs.] implant only) and timing of reconstruction received (immediate vs. intent for delayed) [ Time Frame: Up to 5 years ]
    Between-arm differences in reconstruction complication rates will be assessed separately within each of the six subgroups based on type and timing of reconstruction. Between-arm differences in complication rates will also be assessed within the two broader subgroups of patients who receive implant only and those who receive autologous based reconstruction. Within each subgroup, the comparison will be done using a two-sample Z test of proportions with a two-sided alternative.
  • Reconstructed breast photographic cosmetic scores [ Time Frame: At 24 months ]
    Two year photographic cosmetic scores will be summarized by treatment arm and will be compared across the treatment arms using a Wilcoxon rank-sum test with a two-sided alternative. The proportions of patients with poor global cosmetic score (defined as a cosmetic score of 3: poor or large difference) at 24 months after radiation will be summarized separately by treatment arm and will be compared using a two-sample test of proportions with a two-sided alternative.
  • Reconstructed breast photographic cosmetic scores based on the method and timing of reconstruction received [ Time Frame: At 24 months ]
    Two year photographic cosmetic scores and the proportions of patients with poor global cosmetic score will be assessed separately by timing and method of reconstruction subgroups using similar method described above.
  • Incidence of arm lymphedema as measured by percent change in ipsilateral arm volume post-radiation from its pre-radiation volume [ Time Frame: Up to 5 years ]
    The proportions of patients with arm lymphedema (defined as a change of 10% or greater in ipsilateral arm volume from the pre-radiation therapy [RT] volume) at 2 year post radiation will be summarized and will be compared across the two treatment arms using a two-sample test of proportions (Z test) with a two-sided alternative. Change in ipsilateral arm volume at each of the following time-points: 6, 12, 24 and 60 months post-radiation (relative to pre-RT) will be compared using a two sample t-test with a two-sided alternative. The changes in arm volume at these time points will also be analyzed as a repeated measure using a linear mixed model with patient as the random effect.
  • Physical well-being, psychosocial well-being, sexual well-being, satisfaction with breast/nipples/abdomen, and satisfaction with overall outcome [ Time Frame: At to 24 months ]
    Change in Lymphedema and Breast Cancer Questionnaire and Breast Lymphedema scores at 24 months post-radiation (relative to pre-RT) and patient satisfaction scores as measured by the Breast Questionnaire overall outcome scale will be summarized and will be compared across the treatment arms using a two-sample t-test with a two-sided alternative. Linear mixed models will also be used to assess these scores longitudinally.
  • Patient satisfaction with trial participation by treatment arm as measured by the Was It Worth It Questionnaire [ Time Frame: At 24 months ]
    Was It Worth It questionnaire responses to each of the five questions at 24 months will be summarized and the will be compared across treatment arms using a chi-square tests with a two-sided alternative.
  • Economic analyses [ Time Frame: Up to 5 years ]
    Direct costs of medical care to each patient will be estimated using utilization information from the health care expense survey and the health care utilization survey, along with publicly available Medicare reimbursement rates. In particular, based on the reported number of outpatient visits to the radiation oncologist, medical oncologist, surgeon who performed mastectomy, plastic surgeon or physical therapist, and the number of visits to the emergency room, the number of hospital admissions, and the number of surgical procedures to breast reconstruction, Medicare reimbursement rates can be used to estimate what the direct cost to each patient would be if that patient were covered by Medicare. Generalized linear models will then be used to model these costs as a function of treatment, time on study, and all available baseline patient characteristics to assess the extent to which estimated direct cost is impacted by the type of radiation dosing.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
Official Title  ICMJE RT CHARM: Phase III Randomized Trial of Hypofractionated Post Mastectomy Radiation With Breast Reconstruction
Brief Summary This randomized phase III trial studies how well hypofractionated radiation therapy works in preventing recurrence in patients with stage IIa-IIIa cancer who have undergone mastectomy. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells that remain after surgery and have fewer side effects.
Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate whether the reconstruction complication rate at 24 months post radiation is non-inferior with hypofractionation.

SECONDARY OBJECTIVES:

I. To evaluate the incidence of acute and late radiation complications, based on Common Terminology Criteria for Adverse Events (CTCAE) 4.0 toxicity.

II. To evaluate the local and local regional recurrence rate. III. To compare reconstruction complication rates based on reconstruction method (autologous +/- implant versus [vs] implant only) and timing of reconstruction received (immediate vs. intent for delayed).

TERTIARY OBJECTIVES:

I. To evaluate reconstructed breast photographic cosmetic scores with hypofractionated radiation compared to standard fractionation 24 months after radiation.

II. To evaluate reconstructed breast photographic cosmetic scores 24 months after radiation based on the method and timing of reconstruction received.

III. To estimate the incidence of arm lymphedema by treatment arm. IV. To compare physical well-being, psychosocial well-being, sexual well-being, satisfaction with breast/nipples/abdomen, and satisfaction with overall outcome between the treatment arms at 24 months after radiation.

V. To estimate patient satisfaction with trial participation by treatment arm as measured by the Was It Worth It Questionnaire at 24 months after radiation.

VI. To compare the direct and indirect patient costs for radiation therapy by treatment arm.

VII. To compare patient reported total health care service utilization 12 months after the completion of radiation.

VIII. To compare the economic impact of treatment. IX. To analyze polymorphisms in MDM2 and in genes including TP53, ATM, TGFB1, IL4, IL6, and IL10 and determine correlations with a higher likelihood of adverse radiation reactions (radiation sensitivity) and with toxicities.

X. To analyze polymorphisms in MDM2 and in genes including TP53, ATM, TGFB1, IL4, IL6, and IL10 to determine correlations with secondary endpoints such as local-regional control.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients undergo radiation therapy daily on Monday-Friday for 5-6 weeks.

GROUP II: Patients undergo hypofractionated radiation therapy daily on Monday-Friday for 3-4 weeks.

After completion of study, patients are followed up for 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Ductal Breast Carcinoma
  • Invasive Breast Carcinoma
  • Lobular Breast Carcinoma
  • Medullary Breast Carcinoma
  • Stage II Breast Cancer
  • Stage IIA Breast Cancer
  • Stage IIB Breast Cancer
  • Stage IIIA Breast Cancer
  • Tubular Breast Carcinoma
Intervention  ICMJE
  • Radiation: Radiation Therapy
    Undergo RT
  • Other: Questionnaire Administration
    Ancillary studies
  • Other: Quality-of-Life Assessment
    Ancillary studies
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Radiation: Hypofractionated Radiation Therapy
    Undergo hypofractionated RT
Study Arms  ICMJE
  • Active Comparator: Group I (radiation therapy)
    Patients undergo radiation therapy daily on Monday-Friday for 5-6 weeks.
    Interventions:
    • Radiation: Radiation Therapy
    • Other: Questionnaire Administration
    • Other: Quality-of-Life Assessment
    • Other: Laboratory Biomarker Analysis
  • Experimental: Group II (hypofractionated radiation therapy)
    Patients undergo hypofractionated radiation therapy daily on Monday-Friday for 3-4 weeks.
    Interventions:
    • Other: Questionnaire Administration
    • Other: Quality-of-Life Assessment
    • Other: Laboratory Biomarker Analysis
    • Radiation: Hypofractionated Radiation Therapy
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: January 23, 2018)
880
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2035
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed invasive carcinoma of the breast of any of the following histologies (ductal, lobular, mammary, medullary, or tubular); patients with metaplastic breast cancer are not eligible
  • Patients will be staged according to the TNM staging system

    • For patients not receiving neoadjuvant chemotherapy, pathologic staging must be T0N1-2a, T1N1-2a, T2N1-2a, T3N0-2a, and all M0 status
    • For patients receiving neoadjuvant chemotherapy, clinical pre-chemo staging and post mastectomy pathological staging is required for all patients; patients who have received neoadjuvant chemotherapy and are pathologically cT0-2 and N0 are only eligible if biopsy-proven clinically N1 or N2 disease is documented prior to the start of neoadjuvant chemotherapy; cT3N0 patients or ypT3N0 patients who receive neoadjuvant chemotherapy may be eligible based on clinical or pathological T stage, and do not require pathologically positive lymph nodes
    • Note: Higher of the clinical or pathological T and N stage are used for final staging, if receiving neoadjuvant chemotherapy; all patients with clinical, radiographic or pathological T4, N3 or involved internal mammary disease (N1b, N1c, and N2b) are not eligible
  • No prior therapeutic radiation therapy to the chest, neck or axilla; prior radioactive oral iodine is permitted
  • No prior history of ipsilateral breast cancer (invasive disease or ductal breast carcinoma in situ [DCIS]); lobular carcinoma in situ (LCIS) and benign breast disease is allowed
  • No history of prior or concurrent contralateral invasive breast cancer; benign breast disease, LCIS or DCIS of contralateral breast is allowed
  • No active collagen vascular diseases, such as: systemic lupus erythematous, scleroderma, or dermatomyositis
  • Negative inked histologic margins from mastectomy pathology (no invasive cells at margin)
  • No significant post mastectomy complications in the ipsilateral breast requiring an unplanned re-operation or admission for intravenous (IV) antibiotics; re-operation for margins evaluation, nodal completion and routine reconstruction is acceptable
  • Radiation oncologist intends to treat all target volumes and respect all normal tissues in accordance with the dosimetric constraints described (simulation before registration recommended)
  • Radiation oncologist is planning to treat regional lymph nodes including internal mammary nodes and meet acceptable protocol dosimetric requirements
  • Radiation oncologist is NOT planning to utilize a chest wall/scar boost
  • Patient must have undergone immediate reconstruction at the time of mastectomy or be planning to undergo reconstruction within 18 months after radiation
  • If a tissue expander is utilized it needs to be a fluid filled expander, NO air expander (unless completely deflated) during radiation therapy
  • For patients with diabetes, hemoglobin A1C test must have been performed =< 90 days prior to registration
  • No co-existing medical conditions with life expectancy < 5 years
  • No other malignancy within 5 years of registration with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix
  • Negative serum or urine beta-human chorionic gonadotropin (HCG) in women of child-bearing potential =< 7 days prior to registration; a female of childbearing potential is a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 12 consecutive months
  • Women of child-bearing potential must agree to utilize a form of birth control or agree to undergo sexual abstinence during radiation therapy
  • Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
  • Patients must be able to read and comprehend English, in order to be able to complete study questionnaires; however, patients participating through Canadian Cancer Trials Group (CCTG) institutions who can read and comprehend French are eligible
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Matthew Poppe, MD 801-581-8793 Matthew.Poppe@hci.utah.edu
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03414970
Other Study ID Numbers  ICMJE A221505
NCI-2017-00817 ( Registry Identifier: NCI Clinical Trial Reporting Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Canadian Cancer Trials Group
Investigators  ICMJE
Study Chair: Matthew Poppe, MD Huntsman Cancer Hospital, University of Utah
PRS Account Alliance for Clinical Trials in Oncology
Verification Date June 2020

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