RTOG 9804 - PHASE III TRIAL OF OBSERVATION +/- TAMOXIFEN VS. RT +/- TAMOXIFEN FOR GOOD RISK DUCT CARCINOMA IN-SITU (DCIS) OF THE FEMALE BREAST
UTSW IRB# 062004-003
Principal Investigator: Dan Garwood, MD
Coordinator: Jennifer Sheppard
Contact Number: (214) 648-5536

OBJECTIVES: Radiation therapy, a form of cancer treatment using high-energy x-rays, may decrease the chance of early stage breast cancer coming back. The anti-estrogen hormone tamoxifen also may be appropriate for this condition after a surgeon has carefully removed this small cancer. It has recently been shown that tamoxifen reduces the risk of this cancer returning. Your physician and you will decide if your treatment will include tamoxifen. In this study, observation with or without tamoxifen will be compared to breast radiation therapy with or without tamoxifen.  Number of Participants:   National: 1790 -- Local: 20

KEY ELIGIBILITY CRITERIA:

• Patients must be women.
• The DCIS must be detected by mammogram and must be unicentric.
• Lesions < 2.5 cm. in greatest dimension on mammogram.
• Must be classified as low (NG1) or intermediate (NG2) nuclear grade DCIS, using the Philadelphia Consensus Conference Guidelines (Appendix VII).
• Margins as assessed by the India ink method will be 3 mm or greater.
• A post-operative mammogram will be taken within 12 weeks after the final surgery. It will include magnification views of the study breast and must show no suspicious areas.
• Clinically node negative.
• Patients must be > 26 years of age to avoid the increased potential in the young patient for radiation to induce breast cancer later in life.
• If assigned to Arm 2, radiation must begin within 12 weeks after the final surgery.
• Patients must sign a study-specific consent form prior to randomization.

KEY INELIGIBILITY CRITERIA:

• Patients whose DCIS is palpable at the time of diagnosis, or multi-centric.
• Lesions measuring > 2.5 cm in greatest dimension on mammogram.
• High-grade lesions (NG3) as classified by the Philadelphia Consensus Conference Guidelines.
• Final pathology margins measuring < 3 mm. If the patient undergoes a further re-excision and then meets selective criteria, she may be randomized to this study.
• Pregnant or lactating women because of the potential risk to the fetus or child from breast irradiation.
• Active connective tissue disorders, such as lupus or scleroderma.
• Prior history of any malignancy, except basal or squamous cell skin cancers or in situ carcinoma of the cervix, unless disease-free > 5 years.
• Any prior irradiation or chemotherapy.
• Patients whose post-operative mammogram shows findings for DCIS. If the patient undergoes a further re-excision and has a subsequent negative mammogram, she may be randomized to this study.
• Other hormone therapy at the time of study entry, including raloxifene, hormone-replacement therapy, or birth control pills.
• Tamoxifen begun > 4 weeks prior to diagnosis of DCIS.

SCHEMA (1/15/02)(4/7/04)
The physician specifies tamoxifen use:

*RT Dose: 1.8 Gy per fraction x 28 fractions, for a total dose of 50.0 Gy; OR 2.656 Gy per fraction x 16 fractions, for a total dose of 50.0 Gy; OR 2.656 Gy per fraction x 16 fractions

RTOG 0413 - A RANDOMIZED PHASE II STUDY OF CONVENTIONAL WHOLE BREAST IRRADIATION (WBI) VERSUS PARTIAL BREAST IRRADIATION (PBI) FOR WOMEN WITH STAGE 0, I, or II BREAST CANCER 
UTSW IRB# 052005-007
Principal Investigator: Ann Spangler, MD
Coordinator: Allison Rodarte
Contact Number: (214) 648-5536

OBJECTIVE:To determine whether partial breast irradiation (PBI) limited to the region of the tumor bed following lumpectomy provides equivalent local tumor control in the breast compared to conventional whole breast irradiation (WBI) in the local management of early stage breast cancer. Number of Participants:    National: 3000 -- Local: 36

• The patient must consent to be in the study and must have signed an approved consent form conforming with federal and institutional guidelines.
• Patients must be > 18 years old.
• The patient should have a life expectancy of at least 10 years, excluding her diagnosis of breast cancer.   (Comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer).
• The patient must have stage 0, I, or II breast cancer.  If stage II, the tumor size must be 3 cm or less.
• On histological examination, the tumor must be DCIS or invasive adenocarcinoma of the breast.
• Surgical treatment of the breast must have been lumpectomy.  The margins of the resected specimen must be histologically free of tumor (DCIS and invasive). Re-excision of surgical margins is permitted.
• Gross disease must be unifocal with pathologic (invasive and/or DCIS) tumor size 3 cm or less. (Patients with microscopic multifocality are eligible as long as total pathologic tumor size is 3 cm or less).
• Patients with invasive breast cancer are required to have axillary staging which can include sentinel node biopsy alone (if sentinel node is negative), sentinel node biopsy followed by axillary dissection or sampling with a minimum total of 6 axillary nodes (if sentinel node is positive), or axillary dissection alone (with a minimum of 6 axillary nodes).  (Axillary staging is not required for patients with DCIS).
• The patient must be randomized within 42 days following the last surgery for breast cancer (lumpectomy, re-excision of margins, or axillary staging procedure).
• Patients must have an estrogen receptor (ER) analysis performed on the primary tumor prior to randomization.  If ER analysis is negative, then progesterone receptor (PgR) analysis must be performed.  If ER analysis is positive, PgR analysis is desired but not mandatory. (“Marginal” or “borderline” results [i.e., those not definitively negative] will be considered positive regardless of the methodology used.)
• The target lumpectomy cavity must be clearly delineated and the target lumpectomy cavity/whole breast reference volume must be < 30% based on the postoperative/pre-randomization CT scan.
• Patients are eligible if, based on the postoperative/pre-randomization CT scan, PBI is judged to be technically deliverable by a technique for which the radiation oncology facility has been credentialed.
• At the time of randomization, patients must have had an H & P within 4 months and bilateral mammogram within 6 months.
• Patients with a history of non-breast malignancies are eligible if they have been disease-free for 5 or more years prior to randomization and are deemed by their physician to be at low risk for recurrence.  Patients with the following cancers are eligible if diagnosed and treated within the past 5 years; carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
• Spanish-speaking subjects will be eligible to participate in the study.

KEY INELIGIBILITY CRITERIA:

• T2 (>3.0 cm), T3, stage III, or stage IV breast cancer.
• More than 3 histologically positive axillary nodes.
• Axillary nodes with definite evidence of microscopic or macroscopic extracapsular extension.
• One or more positive non-axillary sentinel node(s). (Note that intramammary nodes are staged as axillary nodes).
• Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters.
• Paget’s disease of the nipple.
• Synchronous bilateral invasive or non-invasive breast cancer.
• History of invasive breast cancer or DCIS. (Patients with a history of LCIS treated by surgery alone are eligible).
• 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).
• Clear delineation of the extent of the target lumpectomy cavity not possible.
• Treatment plan that includes regional nodal irradiation.
• Any treatment with radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to randomization. The only exception is hormonal therapy, which may have been given for no more than total of 28 days anytime after diagnosis and before randomization. For patients who will be receiving chemotherapy, hormonal therapy must stop at or before randomization and resume following completion of chemotherapy. For patients who will not be receiving chemotherapy, hormonal therapy may continue.
• Current therapy with any hormonal agents such as raloxifene (Evista), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Patents are eligible only if these medications are discontinued prior to randomization).
• Breast implants. (Patients who have had implants removed are eligible).
• Prior breast or thoracic RT for any condition.
• Collagen vascular disease, specifically dermatomyositis with CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
• Pregnancy or lactation at the time of proposed randomization. Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy.
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.

SCHEMA