Proton Radiation for Stage II/III Breast Cancer

Tracking Information
First Submitted Date ICMJE	December 14, 2012
First Posted Date ICMJE	January 1, 2013
Last Update Posted Date	January 18, 2018
Study Start Date ICMJE	February 2013
Estimated Primary Completion Date	January 2022 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 26, 2012)	Determination of the rates of acute and late toxicities (acute and late adverse events) resulting from proton therapy radiation treatment. [ Time Frame: 5 years ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01758445 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 26, 2012)	Compare dosimetrically the dose volume histogram (DVH) of the PT plans with conventional external beam plans (either photon/electron intensity modulated radiotherapy(IMRT)plans, 3D-photon plans, or Tomotherapy plans). [ Time Frame: On average at 9 weeks post start of treatment ]; Incidence rates of local control, regional control, metastatic status and disease free overall survival. [ Time Frame: 5 years ]; Compare the different DVH parameters for the targets (D2, Dmean, Dmin, D95, V95, V110) and different OARs (as described later) of the PT plans with the corresponding values of the 3D-conformal radiation therapy (CRT), IMRT and Tomotherapy plans. [ Time Frame: On average at 9 weeks post start of treatment ]; Determine dose distribution of proton therapy to coronary arteries, heart, ipsilateral and contralateral lung, and contralateral breast. [ Time Frame: On average at 9 weeks post start of treatment ]; Determine the incidence of clinically symptomatic coronary artery disease, cardiac morbidity and mortality in general and incidence of secondary malignancy, including contralateral breast cancer [ Time Frame: 5 years ]; Evaluate quality of life results. [ Time Frame: 5 years ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Proton Radiation for Stage II/III Breast Cancer
Official Title ICMJE	Phase II Study of Postoperative, Cardiac-Sparing Proton Radiotherapy for Patients With Stage II/III,Loco-Regional, Non-Metastatic Breast Cancer Requiring Whole Breast or Chest Wall Irradiation With Lymph Node Irradiation
Brief Summary	The purpose of this study is to look at the rates of acute and long term adverse events of postoperative proton radiotherapy for complex loco-regional irradiation in women with loco-regionally advanced breast cancer. This study specifically includes longitudinal follow up to assess the incidence of cardiac mortality and second malignant neoplasms at 10 and 15 years following proton therapy(PT).
Detailed Description	The proposed Phase II study is seeking to build clinical data as a continuation of the original dosimetric analysis published by Ares et al. performed at Paul-Scherrer Institute (PSI). That comparison demonstrated a benefit form proton planning for patients with non-metastatic breast cancer requiring complex, loco-regional, postoperative radiotherapy.1 The advantages of PT were improved target coverage compared to standard photon irradiation and reduced dose to heart, lungs and contralateral breast. The study goal is to demonstrate a "meaningful benefit" of proton therapy for women with loco-regionally advanced breast cancer. The main clinical endpoints of this trial are the reduction of cardiac morbidity and mortality (coronary artery disease, myocardial infarction, cardiac insufficiency) and the reduction of contralateral, second breast cancer. Both adverse events are presently associated with external beam photon therapy. Both goals require longitudinal follow-up of minimum 5-10 years. Despite the logistical challenges of long term follow-up, the effort is needed in view of the compelling preclinical evidence of dose avoidance or even absence of radiation dose to heart and contralateral breast uniquely accomplishable by protons only.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Breast Cancer; Breast Neoplasm; Breast Tumor; Cancer of the Breast
Intervention ICMJE	Radiation: Proton Radiotherapy; Radiation therapy will be given once a day. Minimum of 28 treatments and may receive 6-9 additional treatments as determined by protocol & physician.
Study Arms	Experimental: Proton Radiotherapy; Proton Radiotherapy; Intervention: Radiation: Proton Radiotherapy
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: December 11, 2014)	220
Original Estimated Enrollment ICMJE; (submitted: December 26, 2012)	500
Estimated Study Completion Date	January 2030
Estimated Primary Completion Date	January 2022 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Must sign study-specific, IRB approved informed consent form prior to study entry. Note consent by legally authorized representative is not allowed for this trial.; Must be > = 18 years of age.; Must have a life expectancy of at least 10 years based on age and comorbidities but excluding diagnosis of breast cancer.; Must have pathology proven breast cancer. Pathology must be invasive ductal or lobular; Must meet stage II - III group criteria per AJCC Staging manual 7th edition.; Must have had surgical treatment of the breast - either mastectomy or breast preserving surgery, such as lumpectomy. Re-excision of surgical margins is permitted.; Note: Multicentric breast cancer and Paget's disease of the nipple are permitted. Exclusion Criteria: Weight over 410 pounds.; Non-epithelial breast malignancies such as sarcoma or lymphoma.; Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re-excision, the patient is eligible).; Breast size exceeding the technical limitation of daily set-up reproducibility. This may be center-specific and will be assessed at the discretion of the treating center.; Women with post-surgical temporary breast expanders will require individual assessment. Depending on the manufacturing product and other treatment planning-specific details the patient may be eligible or may be deemed ineligible, as determined by treating investigator.; Prior history of breast cancer.; Prior radiation to the breast or thorax.; Collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.; Pregnancy or lactation at the time of proposed study entry. Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy such as an intrauterine device or condom with spermicide. (Note: Women of childbearing potential must have a negative serum pregnancy test within 3 weeks of study registration).; Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.; Prior history of non-breast malignancies unless they have been disease free for 5 or more years and are deemed by their physician to be at low risk for recurrence. Further, patients who have the following cancers treated within the prior 5 years are permitted: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, basal cell or squamous cell carcinoma of the skin.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Corey Woods, RN, MS, CCRC 630-836-8668 cwoods@pcgresearch.org
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01758445
Other Study ID Numbers ICMJE	BRE008-12
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Proton Collaborative Group
Study Sponsor ICMJE	Proton Collaborative Group
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Chair: Eugen Hug, MD Proton Collaborative Group
PRS Account	Proton Collaborative Group
Verification Date	January 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP