RT CHARM: Phase III Randomized Trial of Hypofractionated Post Mastectomy Radiation With Breast Reconstruction
Overview
- Phase
- Phase 3
- Intervention
- Radiation Therapy
- Conditions
- Ductal Breast Carcinoma
- Sponsor
- Alliance for Clinical Trials in Oncology
- Enrollment
- 898
- Locations
- 1716
- Primary Endpoint
- Proportion of Breast Reconstruction Complications
- Status
- Active, Not Recruiting
- Last Updated
- 2 months ago
Overview
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.
Investigators
Eligibility Criteria
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. N1mic patients are 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). Patients with DCIS at margin are eligible.
Exclusion Criteria
- Not provided
Arms & Interventions
Group I (radiation therapy)
Patients undergo radiation therapy daily on Monday-Friday for 5-6 weeks.
Intervention: Radiation Therapy
Group I (radiation therapy)
Patients undergo radiation therapy daily on Monday-Friday for 5-6 weeks.
Intervention: Questionnaire Administration
Group I (radiation therapy)
Patients undergo radiation therapy daily on Monday-Friday for 5-6 weeks.
Intervention: Quality-of-Life Assessment
Group I (radiation therapy)
Patients undergo radiation therapy daily on Monday-Friday for 5-6 weeks.
Intervention: Laboratory Biomarker Analysis
Group II (hypofractionated radiation therapy)
Patients undergo hypofractionated radiation therapy daily on Monday-Friday for 3-4 weeks.
Intervention: Questionnaire Administration
Group II (hypofractionated radiation therapy)
Patients undergo hypofractionated radiation therapy daily on Monday-Friday for 3-4 weeks.
Intervention: Quality-of-Life Assessment
Group II (hypofractionated radiation therapy)
Patients undergo hypofractionated radiation therapy daily on Monday-Friday for 3-4 weeks.
Intervention: Laboratory Biomarker Analysis
Group II (hypofractionated radiation therapy)
Patients undergo hypofractionated radiation therapy daily on Monday-Friday for 3-4 weeks.
Intervention: Hypofractionated Radiation Therapy
Outcomes
Primary Outcomes
Proportion of Breast Reconstruction Complications
Time Frame: 24 months
The primary endpoint of this trial is the rate of ipsilateral breast reconstruction complications defined (in the protocol in 10.0. Measurement of effect) as; Capsular contracture (Baker Grade III or IV only), Complete failure of the implant/skin flap, Unplanned admission for reconstruction related issue(s) including but not limited to infection, wound healing complication or pain, Unplanned return to the operating room for recon related issue including but not limited to infection, prosthesis exposure, failed reconstruction, implant removal, wound healing complications or contracture management. Note: Routine revisions such as dog-ear corrections, fat grafting, and contralateral breast revision will be recorded, but not counted towards the primary endpoint; ii) Complications related to the contralateral breast will be collected but will not count towards the assessment of the primary endpoint, ipsilateral breast complications will be counted towards the primary endpoint.
Secondary Outcomes
- Incidence of Acute and Late Radiation Complications Based on Common Terminology Criteria for Adverse Events 4.0 Toxicity(5 years)
- Local and Local Regional Recurrence(3 years)
- Local and Local Regional Recurrence-free Survival(3 years)
- Reconstruction Complication Rates Based on Reconstruction Method (Autologous +/- Implant Versus [vs.] Implant Only) and Timing of Reconstruction Received (Immediate vs. Intent for Delayed)(Up to 5 years)
- Reconstructed Breast Photographic Cosmetic Scores(At 24 months)
- Reconstructed Breast Photographic Cosmetic Scores Based on the Method and Timing of Reconstruction Received(At 24 months)
- Incidence of Arm Lymphedema as Measured by Percent Change in Ipsilateral Arm Volume Post-radiation From Its Pre-radiation Volume(Up to 5 years)
- Physical Well-being, Psychosocial Well-being, Sexual Well-being, Satisfaction With Breast/Nipples/Abdomen, and Satisfaction With Overall Outcome(At to 24 months)
- Patient Satisfaction With Trial Participation by Treatment Arm as Measured by the Was It Worth It Questionnaire(At 24 months)
- Economic Analyses(Up to 5 years)