Partial Breast Irradiation With Chemotherapy

Phase I/II Partial Breast Irradiation With Concurrent Chemotherapy

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with cyclophosphamide and doxorubicin after surgery may kill any tumor cells that remain.

PURPOSE: This phase I/II trial is studying the side effects of radiation therapy when given together with cyclophosphamide and doxorubicin and to see how well they work in treating women with stage I or stage II breast cancer who have undergone surgery.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: Doxorubicin; Radiation: radiation

Detailed Description

OBJECTIVES:

• Assess the potential acute and late skin and subcutaneous toxicities in women with resected stage I or II breast cancer treated with partial breast irradiation (PBI) and concurrent cyclophosphamide/doxorubicin (AC) chemotherapy.
• Assess the cosmetic effects of partial breast irradiation/chemotherapy (PBIC) in these patients.
• Assess the local control rate in patients treated with this regimen.

OUTLINE: Patients undergo partial breast radiotherapy once daily, 5 days a week, for 3 weeks. Patients also receive doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment with doxorubicin and cyclophosphamide repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for approximately 10 years.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast by routine hematoxylin and eosin (H&E) staining

  • Primary tumor ≤ 4 cm and 0-3 positive axillary lymph nodes (pathologic T1-2, pathologic N0-N1, M0)

    • Patients with lymph nodes positive only by cytokeratin staining (i.e., H&E negative) are eligible
• No squamous cell carcinoma or sarcoma of the breast

• Patients must have undergone a segmental mastectomy (SM) with a level I and ll axillary dissection or sentinel lymph node biopsy within the past 14 weeks

  • Surgical margins at the time of SM must be negative (> 3 mm) for both invasive carcinoma and for non-invasive ductal carcinoma
• No active local-regional disease
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Sex: female
• Menopausal status not specified
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective non-hormonal contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other serious or poorly controlled medical or psychiatric condition that could be exacerbated by, or complicate compliance with study treatment

PRIOR CONCURRENT THERAPY:

• No prior radiation therapy to the breast
• No prior trastuzumab (Herceptin ®)
• No other concurrent chemotherapy

• No concurrent hormonal therapy except the following:

  • Steroids given for adrenal failure
  • Hormones administered for non-disease-related conditions (e.g., insulin for diabetes, synthroid for hypothyroidism)
  • Intermittent dexamethasone as an antiemetic or premedication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PBI with Concurrent Chemotherapy; Phase I Single Arm study of PBI with concurrent chemotherapy. Primary endpoint is radiation toxicity. The intervention is partial breast radiation with doxorubicin and cyclophosphamide.	Drug: cyclophosphamide; chemotherapy; Other Names: adriamycin; Drug: Doxorubicin; doxorubicin; Other Names: cytoxan; Radiation: radiation; radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Acute, Late Skin, and Subcutaneous Toxicity	Number of participants with Grade 4 toxicity as defined by the following criteria: Acute Skin Toxicity: 0=No change, 1= Follicular, faint, or dull erythema/epilation/dry/desquamation/decreased swelling, 2= Tender or bright erythemal patchy moist desquamation/moderate edema, 3= Confluent moist desquamation other than skin folds, piting edema, 4= Ulceration, hemorrahage, necrosis, Late Skin Toxicity: 0= None, 1= Slight Atrophy, Pigmentation change, some hair loss, 2= Patch atrophy, moderate telangectasias, total hair loss, 3= Marked atrophy, gross telangectasias, 4= Ulceration; Subcutaneous Tissue Toxicity: 0= None, 1= Slight induration (fibrosis) and loss of subcutaneous fat, 2= Moderate fibrosis but asymptomatic; slight field contracture; <10% linear reduction, 3= Severe induration and loss subcutaneous tissue; field contracture >10% linear reduction; 4= Necrosis	up to 5 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Richard C. Zellars, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications and helpful links

General Publications

• Zellars RC, Frassica D, Stearns V, et al.: Phase I/II trial of partial breast irradiation with concurrent dose-dense doxorubicin and cyclophosphamide (ddAC) chemotherapy in early stage breast cancer: report of skin toxicity and cosmetic outcome. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-44, S26, 2007.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 16, 2006
• First Submitted That Met QC Criteria: January 16, 2006
• First Posted (Estimate): January 18, 2006

Study Record Updates

• Last Update Posted (Actual): February 19, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage I breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Doxorubicin
• Other Study ID Numbers: J0381; P30CA006973 (U.S. NIH Grant/Contract); CDR0000446085; 04-03-22-01 (Other Identifier: JHM IRB)