Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer
Randomized Phase 2 Clinical Trial of Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab + Neoantigen Vaccine Vs. Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer
3 other identifiers
interventional
70
1 country
30
Brief Summary
This phase II trial studies how well nab-paclitaxel, durvalumab, and tremelimumab with or without personalized synthetic long peptide vaccine (neoantigen vaccine) works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as nab-paclitaxel, 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. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving nab-paclitaxel, durvalumab, and tremelimumab with or without neoantigen vaccine will work better in treating patients with triple negative breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2021
Longer than P75 for phase_2
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 30, 2018
CompletedFirst Posted
Study publicly available on registry
July 31, 2018
CompletedStudy Start
First participant enrolled
April 13, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 30, 2026
June 12, 2026
April 1, 2026
5.7 years
July 30, 2018
June 11, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
The median PFS in each arm and their 80% confidence intervals will be assessed using Kaplan-Meier product limit methods and compared by log-rank test.
From initiation of Part B to progression or death, assessed at 6 and 12 months
Secondary Outcomes (4)
Incidence of adverse events
Up to day 22
Clinical response rate
Up to 52 weeks
Clinical benefit rate (complete response, partial response, stable disease)
Up to 52 weeks
Overall survival (OS)
Up to 52 weeks
Other Outcomes (1)
Immune response
Up to 52 weeks
Study Arms (2)
Arm I (neoantigen vaccine, durvalumab, nab-paclitaxel)
EXPERIMENTALSee Detailed Description.
Arm II (durvalumab, nab-paclitaxel)
ACTIVE COMPARATORSee Detailed Description.
Interventions
Undergo tumor biopsy
Undergo blood and urine sample collection
Given IV
Given IV
Given IV
Undergo CT scan
Given IV
Given SC
Undergo MRI
Given SC
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have a histologically confirmed diagnosis of metastatic invasive triple negative breast cancer. Patients with clinical and/or radiologic suspicion of metastatic TNBC can be consented prior to this confirmation.
- Estrogen receptor (ER) and progesterone receptor (PR) less than Allred score of 3 OR less than 1% positive staining cells in the invasive component of the tumor.
- HER2 negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+.
- PD-L1 negative by a Clinical Laboratory Improvement Act (CLIA) approved laboratory using compatible assays appropriate for treatment decisions.
- Patients may have measurable or evaluable disease.
- Patients must be willing to undergo biopsy and have accessible lesions for a new biopsy, or they must have sufficient tissue available from a biopsy performed for standard of care (specifications below). If patient does not have enough archived tissue available, a new biopsy is required. A tumor specimen obtained from relapsed primary, metastatic, or locally advanced sites of disease (if applicable) must be submitted. Acceptable samples include core needle biopsies for deep tumor tissue (minimum 4 cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. Formalin-fixed, paraffin-embedded (FFPE) tumor specimens in paraffin blocks are preferred; FFPE tumor tissue sections on slides may be provided if sufficient material (15 x 10μ, unstained) is available. Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable.
- No prior therapy for metastatic TNBC. Patients who have received taxane-based adjuvant therapy are required to have a disease-free interval of at least 12 months after completion of taxane therapy.
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of durvalumab (MEDI4736) and tremelimumab in combination with neoantigen vaccine in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 60%).
- Body weight \> 30 kg.
- Must have a life expectancy of at least 12 weeks.
- Absolute neutrophil count \>= 1,500/mcL.
- Platelets \>= 100,000/mcL.
- Hemoglobin \>= 9.0 g/dL.
- Serum bilirubin =\< 1.5 x institutional upper limit of normal.
- +9 more criteria
You may not qualify if:
- Patients who are not considered to be candidates for carboplatin + gemcitabine for first line therapy of their metastatic triple negative breast cancer are not eligible.
- Patients who have had chemotherapy, radiotherapy (to more than 30% of the bone marrow), or biologic therapy within 30 days (42 days for nitrosoureas or mitomycin C) prior to entering the study.
- Patients who have received prior immunotherapy for metastatic disease.
- Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.
- Patients with grade \>= 2 endocrinological adverse events (AEs), (e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or diabetes mellitus), must have been on a stable dose of supplemental therapy for at least 2 weeks before screening to be eligible for this study, and the endocrinological AE must be stable in the opinion of the treating physician.
- Patients who are receiving any other investigational agents or who have received an investigational agent within the last 30 days.
- Receipt of live attenuated vaccination within 6 months prior to study entry or within 30 days of receiving durvalumab (MEDI4736) and tremelimumab.
- Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment.
- Major surgical procedure within 28 days prior to the first dose of durvalumab (MEDI4736) and tremelimumab. Local surgery of isolated lesions for palliative intent is acceptable.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab (MEDI4736) or tremelimumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids or local steroid injections (e.g. intra-articular injection)
- Systemic corticosteroids at physiological doses which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid
- Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
- Steroids for symptoms from brain metastases as defined.
- Spinal cord compression or active brain metastases and/or carcinomatous meningitis. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to registration are eligible if they meet all of the following criteria:
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Yale University
New Haven, Connecticut, 06520, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607, United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Moffitt Cancer Center at Wesley Chapel
Wesley Chapel, Florida, 33544, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
Wake Forest University at Clemmons
Clemmons, North Carolina, 27012, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Texas Medical Branch
Galveston, Texas, 77555-0565, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
William E Gillanders
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Masking Details
- Treating physicians and patients will be blinded to the results of randomization until the start of Part B.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 30, 2018
First Posted
July 31, 2018
Study Start
April 13, 2021
Primary Completion (Estimated)
December 30, 2026
Study Completion (Estimated)
December 30, 2026
Last Updated
June 12, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.