Testing Olaparib Either Alone or in Combination With Atezolizumab in BRCA Mutant Non-HER2-positive Breast Cancer
A Phase II Open-Label, Randomized Study of PARP Inhibition (Olaparib) Either Alone or in Combination With Anti-PD-L1 Therapy (Atezolizumab; MPDL3280A) in Homologous DNA Repair (HDR) Deficient, Locally Advanced or Metastatic Non-HER2-Positive Breast Cancer
9 other identifiers
interventional
81
1 country
58
Brief Summary
This randomized phase II trial studies how well olaparib with or without atezolizumab work in treating patients with non-HER2-positive breast cancer that has spread to nearby tissue or lymph nodes (locally advanced), that cannot be removed by surgery (unresectable), or that has spread from where it first started (primary site) to other places in the body (metastatic). Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. It is not known whether giving olaparib with or without atezolizumab will work better in patients with non-HER2-positive 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 Mar 2017
Longer than P75 for phase_2
58 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 27, 2016
CompletedFirst Posted
Study publicly available on registry
July 29, 2016
CompletedStudy Start
First participant enrolled
March 30, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2026
November 24, 2025
November 1, 2025
9.4 years
July 27, 2016
November 21, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
The study arms will be compared for duration of response survival with Kaplan-Meier estimates and log-rank tests. The Rothman confidence interval (CI), which is based on Greenwood's variance, Thomas and Grunkemeier CI, and the simultaneous confidence bands by Nair and Hall and Wellner, will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease of the PFS data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.
Time measured from randomization, assessed up to 7 years
Secondary Outcomes (2)
Overall response rate (ORR)
Up to 7 years
Duration of response (DoR)
Time from documentation of tumor response to disease progression, assessed up to 7 years
Other Outcomes (5)
Change in level of tumor infiltrating lymphocytes (TILs)
Baseline up to 7 years
Changes of biomarkers expression using deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)-sequencing
Baseline to up to 7 years
Changes in extent of mutational burden in BRCA1/2
Baseline to up to 7 years
- +2 more other outcomes
Study Arms (2)
Arm I (olaparib)
EXPERIMENTALPatients receive olaparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to Arm II. Patients undergo an x-ray, CT scan, MRI, bone scan, and/or PET scan as well as a biopsy and blood sample collection throughout the trial. Patients may also undergo a bone marrow aspiration and biopsy on study.
Arm II (olaparib, atezolizumab)
EXPERIMENTALPatients receive olaparib as in Arm I and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, bone scan, and/or PET scan as well as a biopsy and blood sample collection throughout the trial. Patients may also undergo a bone marrow aspiration and biopsy on study.
Interventions
Given IV
Undergo a biopsy
Undergo blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo a bone scan
Undergo a CT scan
Undergo MRI
Given PO
Undergo a PET scan
Undergo an x-ray
Eligibility Criteria
You may qualify if:
- Patients must have histologically documented unresectable locally advanced or metastatic non-HER2-positive breast cancer and a known BRCA 1/2 mutation present; both germline and somatic mutations are acceptable, however somatic mutations must be identified by either tumor sequencing of tumor tissue or ctDNA in plasma; patients with BRCA mutations of unknown significance are not allowed
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam
- Prior chemotherapy is allowed, including platinum therapy; patients must not have received chemotherapy for 4 weeks prior to the initiation of study treatment and must have recovery =\< grade 1 from any adverse events from any prior chemotherapy (other than alopecia); patients must not have had nitrosoureas or mitomycin C for 6 weeks prior to the initiation of study treatment
- Prior radiation therapy is allowed; patients must not have received minimal radiation therapy (=\< 5% of their total marrow volume) within 3 weeks prior to the initiation of study treatment; otherwise, patients must not have received radiation therapy (\> 5% of their total marrow volume) within 4 weeks prior to the initiation of study treatment; patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
- Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met: minimum of 12 weeks from the first dose of anti-CTLA-4 and \> 6 weeks from the last dose, and no history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] grade 3 and 4)
- Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) is allowed, provided the following is met: minimum of 2 weeks prior to cycle 1, day 1; patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled; the use of corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
- Prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) is allowed, provided the following is met: minimum of 4 weeks or 5 half-lives of the drug (whichever is longer) prior to cycle 1, day 1
- Patients taking bisphosphonate therapy for symptomatic hypercalcemia are NOT allowed; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
- Prior hormone therapy is allowed; patients must not have received hormone therapy for breast cancer for 2 weeks prior to the initiation of study treatment and must have recovery =\< grade 1 from any adverse events related to these therapies (other than alopecia)
- Prior experimental (non-Food and Drug Administration \[FDA\] approved) therapies and immunotherapies are allowed; patients must not have received these therapies for 4 weeks prior to the initiation of study treatment and must have recovery =\< grade 1 from any adverse events of these therapies (other than alopecia); prior treatment with any PARP inhibitor or any anti-PD-1/anti-PD-L1 antibody is NOT allowed
- Other therapies (e.g. targeted therapy such as cyclin-dependent kinase \[CDK\] inhibitors): patients should have recovered to =\< grade 1 drug related toxicity; they must have completed therapy for either a total of duration equivalent to 5 half-lives of the drug or 28 days, whichever is shorter
- Age \>= 18 years. No dosing or adverse event data are currently available on the use of olaparib in combination with atezolizumab in patients \< 18 years of age; hence, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 6 months
- Absolute neutrophil count \>= 1,500/mcL
- +18 more criteria
You may not qualify if:
- Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have:
- A stable regimen of highly active anti-retroviral therapy (HAART)
- No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
- A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based test
- Patients with prior allogeneic bone marrow transplantation, double umbilical cord blood transplantation (dUCBT) or prior solid organ transplantation
- Patients with known brain metastases should be excluded from this clinical trial except as those described below, because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
- Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
- Evaluable or measurable disease outside the CNS
- No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
- No history of intracranial hemorrhage unless it is confined within a lesion previously noted and secondary to gamma knife or another equivalent radiologic therapeutic
- No history of spinal cord hemorrhage
- No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
- No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1
- Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
- +32 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (58)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
Smilow Cancer Hospital-Orange Care Center
Orange, Connecticut, 06477, United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, 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
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123, United States
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, 37204, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Farmington Health Center
Farmington, Utah, 84025, United States
University of Utah Sugarhouse Health Center
Salt Lake City, Utah, 84106, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
South Jordan Health Center
South Jordan, Utah, 84009, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Patricia M LoRusso
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 27, 2016
First Posted
July 29, 2016
Study Start
March 30, 2017
Primary Completion (Estimated)
August 31, 2026
Study Completion (Estimated)
August 31, 2026
Last Updated
November 24, 2025
Record last verified: 2025-11