Clinical trial NCT01758445: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Breast Neoplasm
Breast Tumor
Cancer of the Breast
Keywords: Breast
Cancer
Radiation
Proton
Lead sponsor: Proton Collaborative Group
Sponsor class: NETWORK
First posted: 2013-01-01
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Determination of the rates of acute and late toxicities (acute and late adverse events) resulting from proton therapy radiation treatment.
timeFrame: 5 years
Secondary outcomes:
measure: 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).
timeFrame: On average at 9 weeks post start of treatment
measure: Incidence rates of local control, regional control, metastatic status and disease free overall survival.
timeFrame: 5 years
measure: 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.
timeFrame: On average at 9 weeks post start of treatment
measure: Determine dose distribution of proton therapy to coronary arteries, heart, ipsilateral and contralateral lung, and contralateral breast.
timeFrame: On average at 9 weeks post start of treatment
measure: Determine the incidence of clinically symptomatic coronary artery disease, cardiac morbidity and mortality in general and incidence of secondary malignancy, including contralateral breast cancer
timeFrame: 5 years
measure: Evaluate quality of life results.
timeFrame: 5 years
Other outcomes:
Locations:
city: Warrenville
country: United States
facility: Northwestern Medicine Chicago Proton Center
state: Illinois
city: Baltimore
country: United States
facility: Maryland Proton Treatment Center
state: Maryland
city: Somerset
country: United States
facility: Princeton ProCure Managment LLC
state: New Jersey
city: Oklahoma City
country: United States
facility: Oklahoma Proton Center
state: Oklahoma
city: Hampton
country: United States
facility: Hampton University Proton Therapy Institute
state: Virginia
Study officials:
affiliation: Proton Collaborative Group
name: Eugen Hug, MD
role: STUDY_CHAIR
References: