Proton Radiation for Stage II/III Breast Cancer

• ClinicalTrials.gov Identifier: NCT01758445
• Recruitment Status: Active, not recruiting
• First Posted: January 1, 2013
• Last Update Posted: July 12, 2019
• Sponsor: Proton Collaborative Group
• Information provided by (Responsible Party): Proton Collaborative Group

Tracking Information

• First Submitted Date: December 14, 2012
• First Posted Date: January 1, 2013
• Last Update Posted Date: July 12, 2019
• Study Start Date: February 2013
• Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Proton Radiation for Stage II/III Breast Cancer
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer
• Breast Neoplasm
• Breast Tumor
• Cancer of the Breast

Intervention

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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: December 11, 2014): 220
• Original Estimated Enrollment (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

Inclusion Criteria:

1. 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.
2. Must be > = 18 years of age.
3. Must have a life expectancy of at least 10 years based on age and comorbidities but excluding diagnosis of breast cancer.
4. Must have pathology proven breast cancer. Pathology must be invasive ductal or lobular
5. Must meet stage II - III group criteria per AJCC Staging manual 7th edition.
6. Must have had surgical treatment of the breast - either mastectomy or breast preserving surgery, such as lumpectomy. Re-excision of surgical margins is permitted.
7. Note: Multicentric breast cancer and Paget's disease of the nipple are permitted.

Exclusion Criteria:

1. Weight over 410 pounds.
2. Non-epithelial breast malignancies such as sarcoma or lymphoma.
3. 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).
4. 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.
5. 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.
6. Prior history of breast cancer.
7. Prior radiation to the breast or thorax.
8. Collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
9. 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).
10. Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
11. 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, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01758445
• Other Study ID Numbers: 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: Proton Collaborative Group
• Collaborators: Not Provided

Investigators

• Study Chair: Eugen Hug, MD; Proton Collaborative Group

• PRS Account: Proton Collaborative Group
• Verification Date: July 2019