Research & Trial Information

SCHEMA EA1131

Protocol#: ECOG – EA1131

Cancer Type: Breast Adjuvant Triple Neg. Following Neo-Adjuvant Chemotherapy

Patient Eligibility:

1. Age ≥ 18 years.
2. ECOG Performance Status 0 or 1 within 2 weeks prior to screening.

3. Female and male patients must have histologically confirmed invasive breast cancer.

4. Clinical stage II or III at diagnosis, based on initial evaluation by clinical examination and/or breast imaging; no metastatic disease allowed.
5. ER- and PR- and HER2 negative.

6. Patients must have completed neoadjuvant taxane +/- anthracycline. Patients must NOT have received cisplatin or carboplatin or capecitabine as part of their neoadjuvant therapy regimen.

7. Must have completed definitive resection of primary tumor.

8. Post neoadjuvant chemotherapy, patients must be found to have residual invasive cancer in the breast at the time of definitive surgery. Residual cancer is defined as a contiguous focus of residual invasive cancer, in the breast, measuring ≥ 1 cm in diameter, and with more than minimal cellularity, as per local pathologist determination. Please note that in patients that have multifocal or multicentric residual tumors these lesions cannot be added up; the biggest lesion has to measure ≥ 1 cm in diameter. This is required due to constraints in DNA extraction for PAM50 analysis.

9. Radiotherapy may be given before or after protocol treatment per standard of care guidelines. When radiotherapy is planned prior to protocol treatment administration, patients may be registered and screened while receiving radiation.

10. No history of TNBC invasive breast cancer within 5 years of enrollment, no concurrent malignancies of any sort.

11. No clinically significant infections as judged by the treating investigator.

12. Patients with active grade 2 neuropathy are ineligible.

13. Adjuvant chemotherapy after surgery other than that specified in this protocol is not allowed. LHRH agonists and adjuvant bisphosphonate or denosumab use is allowed.

14. Patients must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen from the residual disease on the definitive surgical specimen available for PAM50 analysis for stratification.

Research & Trial Information

SCHEMA S1418 BR006

Protocol#:  SWOG – S1418/BR006

Cancer Type: Breast Adjuvant

Patient Eligibility:

1. Patients must have histologically confirmed ER-, PR- and HER2-negative breast cancer (triple-negative, TNBC) or ER- and PR- weakly positive and/or HER2- equivocal status and must not have received and not be planning to receive adjuvant anti-HER2 or endocrine therapies after completion of neoadjuvant chemotherapy. Patients who are HER2-positive are ineligible. HER2-negative and HER2-equivocal cases that do not receive HER2-targeted therapy are eligible. Patients with weakly ER or PR positive disease, defined as ER and/or PR less than or equal to (≤) 5% by immunohistochemistry, are eligible if the treating physician considers the patient not eligible for adjuvant endocrine therapy. Residual disease must be ≥ 1 cm in greatest dimension, and/or have positive lymph nodes (ypN1mi, ypN1, ypN2, ypN3) observed on pathologic exam.
2. Patients must not have metastatic disease and/or locally recurrent disease.
3. It is preferred that axillary lymph node sampling is performed after completion of neoadjuvant chemotherapy to allow more accurate assessment of pathologic response. Patients must have a complete axillary lymph node dissection (ALND) after neoadjuvant chemotherapy.
4. Patients must have a minimum of five, available unstained formalin-fixed paraffin-embedded (FFPE) slides (4-5 micron thickness) from the residual (post-neoadjuvant) invasive tumor in primary site or lymph node.
5. Patients must have had neoadjuvant chemotherapy followed by surgery. The choice of neoadjuvant chemotherapy is determined by the treating physician. Patients who cannot complete all planned treatment cycles for any reason are considered high risk and therefore are eligible for the study if they have residual disease.
6. Patients may receive post-operative (adjuvant) chemotherapy for up to 24 weeks of duration (e.g. 8 cycles of capecitabine as in the CREATE-X trial) after completion of surgery at the discretion of the treating physician.
7. Patients must have completed their final breast surgery (rendering them free from disease) with clear resection margins for invasive cancer and DCIS.
8. Patients for whom radiation therapy (RT) to the affected breast or chest wall and regional nodal areas is clinically indicated as per NCCN treatment guidelines, should receive routine RT after randomization when possible, and receive MK-3475 (pembrolizumab) concurrent with RT, if randomized to the experimental arm.
9. Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs.
10. Patients must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol.
11. Patients must be ≥ 18 years of age.
12. Patients must have Zubrod Performance Status ≤ 2.
13. Patients must not have active autoimmune disease that has required systemic treatment in past 2 years.
14. Patients must not have received live vaccines within 30 days prior to registration.
15. No other prior invasive malignancy is allowed except for the following: adequately treated basal (or squamous cell) skin cancer, in situ breast or cervical cancer. Stage I or II invasive cancer treated with a curative intent without evidence of disease recurrence for at least five years.

Research & Trial Information

SCHEMA NRG BR003

Protocol#: NRG – BR003

Cancer Type: Breast Adjuvant

Patient Eligibility:

1. The trial is open to female and male patients.
2. Age ≥ 18 years.
3. ECOG Performance Status of 0 or 1.
4. The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
5. All of the following staging criteria must be met: By pathologic evaluation, primary tumor must be pT1-3; By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN2b, pN3a, or pN3b.  If pN0, pathological tumor must be ≥ 3.0 cm.
6. The tumor must have been determined to be HER2-negative.
7. The tumor must have ER and PgR status assessed using current ASCO/CAP Guidelines. Patients are eligible if the tumor staining meets one of the following criteria:  ER-negative and PgR-negative by ASCO/CAP guidelines, OR  ER or PgR stains are positive in 1-9% of cells and neither is positive in ≥ 10% of cells.
8. The patient must have undergone either a mastectomy (total, skin-sparing, or nipple-sparing) or lumpectomy.
9. For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist.
10. For patients who undergo mastectomy, the margins must be free of residual gross tumor. (Patients with microscopic positive margins are eligible as long as post-mastectomy RT of the chest wall will be administered.)
11. The patient must have completed one of the procedures for evaluation of pathologic nodal status: • Sentinel lymphadenectomy alone:

    − If pathologic nodal staging based on sentinel lymphadenectomy is pN0 or pN1b;

    − If pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1a and the patient has undergone breast conserving surgery (with planned breast radiotherapy), the primary tumor must be T1 or T2 by pathologic evaluation and the nodal involvement must be limited to 1 or 2 positive nodes.

    • Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive; or

    • Axillary lymphadenectomy with or without SN isolation procedure.

12. The interval between the last surgery for breast cancer (including re-excision of margins) and randomization must be no more than 60 days.
13. No  T4 tumors including inflammatory breast cancer.
14. No definitive clinical or radiologic evidence of metastatic disease. Required imaging studies must have been performed within 90 days prior to randomization.
15. No synchronous or previous contralateral invasive breast cancer. (Patients with synchronous and/or previous contralateral DCIS or LCIS are eligible.)
16. No previous history of ipsilateral invasive breast cancer or ipsilateral DCIS. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
17.  No history of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization.
18.  No previous therapy with anthracyclines or taxanes for any malignancy.
19. No chemotherapy administered for the currently diagnosed breast cancer prior to randomization.
20. No uncontrolled hypertension.
21. No use of any investigational product within 4 weeks prior to randomization.

Research & Trial Information

SCHEMA A011502

Protocol#: A011502

Cancer Type: Breast – Adjuvant

Patient Eligibility:

1. Histologic documentation of women or men with HER2 negative breast carcinoma and free of recurrence.  If neoadjuvant therapy was received, either initial clinical stage (determined by physical and or radiologic examination) or post-operative pathologic stage can be used for eligibility purposes, with the higher stage determining eligibility. Histologic documentation of node positivity is required for ER/PR positive tumors. Bilateral or synchronous breast cancers are allowed, as long as both cancers are HER2 negative and at least one of the cancers meets eligibility.
2. If ER and PR negative, tumor must be node positive or >2 cm and node negative. Patients must be registered within 18 months of diagnosis. pN1mic is eligible. If ER and/or PR positive, tumor must be node positive and within 10 years of diagnosis. pN1mic is eligible.
3. Prior adjuvant treatment with chemotherapy and/or endocrine therapy, as determined by the treating physician, is allowed. The last dose of chemotherapy or radiation therapy must be at least 30 days prior to study registration. Concurrent hormonal therapy is allowed.
4. Regular NSAID/aspirin use at any dose (including baby aspirin) (defined as ≥ 5 days per week) is allowed if aspirin and/or NSAIDs are stopped for 30 days prior to study entry and throughout the study period. Participants will be encouraged to use acetaminophen for minor pain and fever.
5. Age > 18 and < 70 years of age.
6. ECOG performance status 0-2.
7. Patients with a prior history of gastric/duodenal ulcers documented on endoscopy can be enrolled as long as the ulcers did not causeNo history of GI bleeding requiring a blood transfusion, endoscopic or operative intervention.bleeding requiring a blood transfusion/major intervention.
8. No history of GI bleeding requiring a blood transfusion, endoscopic or operative intervention.
9. No history of any prior stroke (hemorrhagic or ischemic).
10. No concurrent anticoagulation with warfarin, heparin/heparin analogues, clopidogrel, direct thrombin inhibitors, or direct factor XA inhibitors.
11. No history of atrial fibrillation or myocardial infarction.
12. No history of grade 4 hypertension, defined as hypertension resulting in life-threatening consequences (e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis).
13. No chronic (duration >30 days) daily use of oral steroids. Inhaled or topical steroids are allowed.
14. No known allergy to aspirin.
15. No prior invasive malignancy of any type within the past 5 years except for current diagnosis of breast cancer, and any prior diagnosis of basal or squamous cell carcinoma of the skin.
16. Prior history of in situ carcinoma is allowed.
17. Concurrent enrollment on a non-chemotherapy treatment trial will be allowed, as long as that trial allows concurrent daily aspirin use.
18. No history of metastatic breast cancer.