Trials / Recruiting

RecruitingNCT06058377

Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer

Phase III Trial Of Neoadjuvant Durvalumab (NSC 778709) Plus Chemotherapy Versus Chemotherapy Alone For Adults With MammaPrint High 2 Risk (MP2) Hormone Receptor (HR) Positive / Human Epidermal Growth Factor Receptor (HER2) Negative Stage II-III Breast Cancer

Status: Recruiting
Phase: Phase 3
Study type: Interventional
Enrollment: 3,680 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase III trial compares the addition of an immunotherapy drug (durvalumab) to usual chemotherapy versus usual chemotherapy alone in treating patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as paclitaxel, doxorubicin, and cyclophosphamide 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. There is some evidence from previous clinical trials that people who have a MammaPrint High 2 Risk result may be more likely to respond to chemotherapy and immunotherapy. Adding durvalumab to usual chemotherapy may be able to prevent the cancer from returning for patients with MP2 stage II-III hormone receptor positive, HER2 negative breast cancer.

Detailed description

PRIMARY OBJECTIVE: I. To compare breast cancer event-free survival between participants randomized to standard of care neoadjuvant chemotherapy alone versus standard of care neoadjuvant chemotherapy concurrent with durvalumab. SECONDARY OBJECTIVES: I. To compare pathologic complete response rates (ypT0/is, ypN0) in participants randomized to standard of care chemotherapy alone versus (vs.) standard of care neoadjuvant chemotherapy concurrent with durvalumab. II. To compare residual cancer burden distribution between participants randomized to standard of care neoadjuvant chemotherapy vs. standard of care neoadjuvant chemotherapy concurrent with durvalumab. III. To compare distant relapse-free survival between participants randomized to standard of care neoadjuvant chemotherapy vs. standard of care neoadjuvant chemotherapy concurrent with durvalumab. IV. To compare overall survival between participants randomized to standard of care neoadjuvant chemotherapy vs. standard of care neoadjuvant chemotherapy concurrent with durvalumab. V. To compare the frequency and severity of toxicities between participants randomized to standard of care neoadjuvant chemotherapy vs. standard of care neoadjuvant chemotherapy concurrent with durvalumab among those who initiate the assigned treatment. PRIMARY QUALITY OF LIFE (QOL) OBJECTIVES: I. To compare the change in fatigue (Patient Reported Outcomes Measurement Information System \[PROMIS\] Fatigue) experienced by participants randomized to neoadjuvant durvalumab plus chemotherapy vs. participants randomized to chemotherapy alone at completion of active treatment (at 20 weeks from baseline). II. To compare the change in global physical health (PROMIS Global Health) experienced by participants randomized to neoadjuvant durvalumab plus chemotherapy vs participants randomized to chemotherapy alone at completion of active treatment (at 20 weeks from baseline). SECONDARY QOL OBJECTIVES: I. To compare the change in fatigue and global physical health experienced by participants randomized to neoadjuvant durvalumab plus chemotherapy vs participants randomized to chemotherapy alone during treatment (at 12 weeks from baseline). II. To compare the changes in global physical health and fatigue subsequent to treatment (at years 1 and 2) between the two randomized study arms. III. To compare the changes in global mental health (PROMIS Global Health) during active treatment (weeks 12, 20) and subsequent to treatment (at years 1 and 2) between the two randomized study arms. IV. To compare the severity and frequency of treatment-related symptoms using Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) items (diarrhea, nausea, cough, shortness of breath, rash, and musculoskeletal pain) over time experienced by participants receiving neoadjuvant durvalumab plus chemotherapy versus chemotherapy alone. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: STEP 1: Patients without a known MP2 score undergo MammaPrint testing on a previously-collected tissue sample. Patients with MP2 score proceed to STEP 2. STEP 2: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive paclitaxel intravenously (IV) 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 on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. 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 on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. All 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 standard of care (SOC) surgery and undergo collection of blood samples throughout the study. After completion of study treatment, patients are followed until death or 10 years, whichever occurs first.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo optional collection of tissue and/or blood
DRUG	Cyclophosphamide	Given IV
DRUG	Doxorubicin	Given IV
BIOLOGICAL	Durvalumab	Given IV
OTHER	Genetic Testing	Undergo MammaPrint testing
PROCEDURE	Mammography	Undergo mammography
DRUG	Paclitaxel	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies

Timeline

Start date: 2023-11-27
Primary completion: 2026-05-31
Completion: 2026-05-31
First posted: 2023-09-28
Last updated: 2026-04-16

Locations

532 sites across 2 countries: United States, Puerto Rico

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06058377. Inclusion in this directory is not an endorsement.