Radiation Therapy and Sequential or Concurrent Combination Chemotherapy in Treating Patients with Early Stage Breast Cancer

This randomized phase II trial studies how well radiation therapy and sequential or concurrent combination chemotherapy works in treating patients with early stage breast cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether radiation therapy is more effective with sequential or concurrent combination chemotherapy in treating early stage breast cancer.

Inclusion Criteria

• Patient must have histologically confirmed (by routine hematoxylin and eosin [H&E] staining) invasive adenocarcinoma of the breast
• Primary tumor =< 4 cm and 0-3 positive axillary lymph nodes (T1-2, N0-1, M0)
• Margin negative surgery
• For subjects with two breasts, they must have had a bilateral mammogram prior to surgery
• Patient must have a medical oncology consult with the recommendation of chemotherapy; recommended regimens are as follows: cyclophosphamide and doxorubicin (AC); Taxotere, doxorubicin and cyclophosphamide (TAC); Taxotere and cyclophosphamide (TC); or Taxotere, carboplatin and trastuzumab (TCH) prior to registration; the use of additional chemotherapy, hormonal therapy or trastuzumab after the initial regimen is at the discretion of the medical oncologist; other primary regimens are possible but the principal investigator (PI) must be notified prior to enrollment
• Partial breast irradiation must be scheduled to begin less than 71 days from the last breast surgical procedure
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Women of child-bearing potential must have a negative (urine or blood) pregnancy test within 6 weeks prior to start of protocol therapy; women of child-bearing potential must also use effective non-hormonal contraception while undergoing radiation therapy
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have received neoadjuvant chemotherapy or neoadjuvant hormonal therapy for the current cancer
• Patients with squamous cell cancer or sarcomas of the breast
• Patients who have active local-regional disease prior to registration
• Patient with a prior malignancy from which the patient has been disease-free for less than 5 years; notable exceptions to this are adequately treated squamous or basal cell cancer of the skin and in-situ cervical cancer
• Patient is pregnant
• Patient has a serious medical or psychiatric illness which prevents informed consent or adherence with treatment
• Study team (PI, co-investigator [I], and/or research nurse) may deny enrollment if in the study team’s opinion, the candidate may not be adherent to the treatment protocol including scheduled follow-ups

PRIMARY OBJECTIVES:

I. Non-inferiority of partial breast irradiation (PBI) and concurrent compared to sequential chemotherapy with respect to acute grade 3-4 radiation toxicity.

SECONDARY OBJECTIVES:

I. Evaluate and compare any first tumor recurrence (local plus distant) between arms of the study.

II. Evaluate long term toxicity with concurrent chemotherapy and compare between arms of the study.

III. Evaluate and compare ipsilateral breast tumor reocurrence (IBTR), local recurrence, distant recurrence, and disease free survival.

IV. Give a description of the risks and benefits observed in each arm of the study over the duration of the trial.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo external beam radiation therapy (EBRT) on weekdays for a total of 15 fractions. After completion of EBRT, patients receive cyclophosphamide and doxorubicin hydrochloride; docetaxel, cyclophosphamide and doxorubicin hydrochloride; docetaxel and cyclophosphamide; or docetaxel, carboplatin, and trastuzumab at the discretion of the treating Medical Oncologist.

ARM II: Patients undergo EBRT as in Arm I. Within 7 days of the start of radiation therapy, patients also receive combination chemotherapy as in Arm I.

After completion of study treatment, patients are followed up at 1-2 weeks, 3-4 months, 6-7 months, and then every 6-12 months for 9 years.

Lead Organization
Indiana University / Melvin and Bren Simon Cancer Center

Principal Investigator
Richard C. Zellars