Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, HER2-Negative Breast Carcinoma
About this trial
This is an interventional treatment trial for Anatomic Stage II Breast Cancer AJCC v8
Eligibility Criteria
Inclusion Criteria: STEP 1: REGISTRATION (SCREENING): Participants must have histologically confirmed estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (hormone receptor positive) and HER2 negative breast cancer, as per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines NOTE: Participants with HER2 positive disease by ASCO CAP guidelines are ineligible. HER2 negative and HER2 low or equivocal cases as per ASCO CAP guidelines that do not receive HER2 targeted therapy are eligible STEP 1: REGISTRATION (SCREENING): Participants must have clinical stage II or III breast cancer NOTE: Participants with inflammatory breast cancer are eligible STEP 1: REGISTRATION (SCREENING): Participants must not have metastatic disease (i.e., must be clinically M0 or Mx) Systemic staging studies with imaging should follow routine practice as per National Comprehensive Cancer Network (NCCN) and ASCO guidelines STEP 1: REGISTRATION (SCREENING): Participants must not have locally recurrent breast cancer STEP 1: REGISTRATION (SCREENING): Participants with multifocal disease or synchronous primary tumors are eligible, however, all tumors must be hormone receptor positive and HER2 negative per ASCO CAP guidelines. It is sufficient to have MP2 status on at least one of the lesions Participants must have either adequate tissue available to submit on-study or a prior known MammaPrint Index Score that is MP2 status Submitting tissue for on-study MammaPrint testing: Participants must have a minimum of ten, unstained formalin-fixed paraffin-embedded (FFPE) slides (4-5 micron thickness) available from initial tumor biopsy for MammaPrint assessment NOTE: Participants must agree to have this tissue submitted to Agendia for MammaPrint Index Scoring and to have subsequent results disclosed to SWOG Cancer Research Network OR Submitting prior known MammaPrint Index Score: If a MammaPrint Index Score report from within the last 12 weeks is already known and is MP2 status, the participant must be registered to Step 2 immediately following Step 1 registration provided they meet all other criteria. MP2 status is defined as a MammaPrint Index score between negative 1.0 and negative 0.57 (-1.0 to -0.57, including negative 0.57) tested from initial tumor biopsy NOTE: Participants must agree to have their commercial MammaPrint Index Score disclosed to Southwest Oncology Group (SWOG) Cancer Research Network NOTE: Participants with prior known MammaPrint result that is not MP2 status should not be enrolled to either step of this study STEP 1: REGISTRATION (SCREENING): Participants must not have received any prior treatment for their current breast cancer, including chemotherapy, immunotherapy, biologic or hormonal therapy, and must be candidates for doxorubicin, paclitaxel, and durvalumab therapy STEP 1: REGISTRATION (SCREENING): Participants must be >= 18 years old at the time of registration STEP 1: REGISTRATION (SCREENING): Participants must have a complete medical history and physical exam within 28 days prior to Step 1 Registration STEP 1: REGISTRATION (SCREENING): Participants must have body weight > 30 kg STEP 1: REGISTRATION (SCREENING): Participants must have Zubrod Performance Status of 0-2 STEP 1: REGISTRATION (SCREENING): Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial STEP 1: REGISTRATION (SCREENING): Participant must not have medical contraindications to receiving immunotherapy, including history of non-infectious pneumonitis that required steroids or active autoimmune disease that has required systemic treatment with disease modifying agents, corticosteroids or immunosuppressive drugs in the past two years. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intra-articular steroid injections are allowed STEP 1: REGISTRATION (SCREENING): NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations STEP 2: RANDOMIZATION: Participants must have met all eligibility criteria for Step 1 Registration STEP 2: RANDOMIZATION: Participants must have MP2 MammaPrint result For participants submitting tissue for on-study MammaPrint testing: Participants must be registered to Step 2: Randomization within 84 calendar days (12 weeks) after receiving an MP2 status from the MammaPrint Index score. MP2 status is defined as a MammaPrint Index score between negative 1.0 and negative 0.57 (-1.0 to -0.57, including negative 0.57) from initial tumor biopsy OR Submitting commercial MammaPrint Index Score: If a MammaPrint Index Score report from within the last 12 weeks is already known and is MP2 status, the participant must be registered to Step 2 immediately following Step 1 registration provided they meet all other criteria. MP2 status is defined as a MammaPrint Index score between negative 1.0 and negative 0.57 (-1.0 to -0.57, including negative 0.57) tested from initial tumor biopsy STEP 2: RANDOMIZATION: Participants must not have received live vaccines within 28 days prior to study Step 2: Randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines and coronavirus disease 2019 (COVID-19) vaccines are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed STEP 2: RANDOMIZATION: Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study STEP 2: RANDOMIZATION: Participant must have Zubrod Performance Status of 0-2 STEP 2: RANDOMIZATION: Participants must not have a history of (non-infectious) pneumonitis that required steroids or evidence of active pneumonitis within two years prior to Step 2: Randomization STEP 2: RANDOMIZATION: Participants must not have active autoimmune disease that has required systemic treatment in the past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) prior to Step 2: Randomization. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intra-articular steroid injections are allowed STEP 2: RANDOMIZATION: Participant must have a complete medical history and physical exam within 28 days prior to Step 2: Randomization STEP 2: RANDOMIZATION: Leukocytes >= 3 x 10^3/uL (within 28 days prior to Step 2: Randomization) STEP 2: RANDOMIZATION: Absolute neutrophil count >=1.5 x 10^3/uL (within 28 days prior to Step 2: Randomization) STEP 2: RANDOMIZATION: Platelets >= 100 x 10^3/uL (within 28 days prior to Step 2: Randomization) STEP 2: RANDOMIZATION: Total bilirubin =< institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to Step 2: Randomization) STEP 2: RANDOMIZATION: AST/ALT =< 3 × institutional ULN (within 28 days prior to Step 2: Randomization) STEP 2: RANDOMIZATION: Participants must have a serum creatinine =< the institutional ULN (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to Step 2: Randomization STEP 2: RANDOMIZATION: Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better STEP 2: RANDOMIZATION: Participants must not have uncontrolled diabetes in the opinion of the treating investigator within 28 days prior to Step 2: Randomization STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have an undetectable viral load on the most recent test results obtained within 6 months prior to Step 2: Randomization STEP 2: RANDOMIZATION: Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on the most recent test results obtained while on suppressive therapy within 6 months prior to Step 2: Randomization, if indicated STEP 2: RANDOMIZATION: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load on the most recent test results obtained within 6 months prior to Step 2: Randomization, if indicated STEP 2: RANDOMIZATION: Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process and must have a negative pregnancy test at screening. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen STEP 2: RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System STEP 2: RANDOMIZATION: Participants who can complete questionnaires in English, or Spanish must be offered the opportunity to participate in the Quality of Life study STEP 2: RANDOMIZATION: NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system STEP 2: RANDOMIZATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
Sites / Locations
- SWOG
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Active Comparator
Experimental
Step 1 (MammaPrint testing)
Step 2, Arm 1 (chemotherapy)
Step 2, Arm 2 (chemotherapy, durvalumab)
Patients without a known MP2 score undergo MammaPrint testing on a previously-collected tissue sample. Patients with MP2 score proceed to STEP 2.
Patients receive paclitaxel IV over 30-60 minutes on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery, and undergo collection of blood samples prior to STEP 2 treatment, after cycle one of chemotherapy, and one month post-SOC surgery.
Patients receive paclitaxel IV over 30-60 minutes on days 1 and 8 of every cycle and durvalumab IV over 60 minutes on day 1 of every other cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of every other cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery, and undergo collection of blood samples prior to STEP 2 treatment, after cycle one of chemotherapy, and one month post-SOC surgery.