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AzTrials

Anatomic Stage III Breast Cancer AJCC v8Phase 2NCT02849496

Testing Olaparib Either Alone or in Combination With Atezolizumab in BRCA Mutant Non-HER2-positive Breast Cancer

A Phase 2 study testing Atezolizumab, Biopsy Procedure and Biospecimen Collection in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by National Cancer Institute (NCI) at 58 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Biopsy Procedure and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
89 participants
Where
58 sitesUnited States
Study dates
30 Mar 2017to 26 Aug 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Leukocytes >= 3,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN) if no liver metastasis; =< 5 x upper ULN if liver metastasis present
  • Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN for patients with documented liver involvement or bone metastases)
  • Creatinine clearance >= 51 mL/min/1.73 m^2 by Cockcroft-Gault
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
  • No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) on peripheral blood smear when performed as clinically indicated
  • Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression)
  • Administration of atezolizumab and/or olaparib may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential and men must agree to use highly effective contraception prior to study entry, for the duration of study participation, and for at least 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use two highly effective forms of contraception in combination prior to the study, for the duration of study participation, and for at least 5 months (150 days) after completion of atezolizumab and/or olaparib administration; women of child-bearing potential: negative serum pregnancy test within 14 days of study treatment and confirmed prior to treatment on day 1; postmenopausal or evidence of non-childbearing status for women of childbearing potential; postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
  • Radiation-induced oophorectomy with last menses > 1 year ago
  • Chemotherapy-induced menopause with > 1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Ability to understand and the willingness to sign a written informed consent document
  • Subject is able to swallow and retain oral medication and does not have uncontrolled emesis or gastrointestinal disorders likely to interfere with absorption of the study medication
  • Patients crossing over from monotherapy to combination therapy do not have to be fully rescreened, as they would have just had tumor assessments and would already have had baseline electrocardiographies (ECGs), etc; however, they do need to meet performance status, organ function, and blood parameters and not meet any of the exclusion criteria
  • 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

Who cannot join

  • 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)
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  • 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:
  • Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
  • No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1
  • Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib and atezolizumab; patients with a known hypersensitivity to olaparib or any of the excipients of the product
  • Prior treatment with any PARP inhibitor or any anti-PD-1/anti-PD-L1 antibody
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, lichen sclerosis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
  • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted if recovered
  • Major surgical procedure within 28 days prior to cycle 1, day 1 and patients must have recovered from any effects of any major surgery; anticipation of need for a major surgical procedure during the course of the study
  • Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab
  • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks prior to cycle 1, day 1 or at any time during the study
  • Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection; examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression, superior vena cava syndrome, symptomatic congestive heart failure, unstable angina pectoris, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent and would limit compliance with study requirements
  • Pregnant women are excluded from this study because olaparib and atezolizumab have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib and atezolizumab, breastfeeding should be discontinued if the mother is treated with olaparib and atezolizumab
  • Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1
  • Patients with active seizures or a history of uncontrolled seizure disorder, including focal or generalized seizure within the past year
  • Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumab
  • Resting ECG with corrected QT (QTc) > 470 msec or family history of long QT syndrome
  • Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil); the required washout period prior to starting olaparib is 2 weeks; because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated drug information reference; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil); the required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents; because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated drug information reference; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study

Trial locations and contacts

58 sites in 1 country.

58 sites in 1 country

United States58 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Farmington Health Center

    Farmington, Utah, 84025

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Smilow Cancer Hospital-Orange Care Center

    Orange, Connecticut, 06477

  • University of Chicago Medicine-Orland Park

    Orland Park, Illinois, 60462

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • University of Utah Sugarhouse Health Center

    Salt Lake City, Utah, 84106

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • UC San Diego Medical Center - Hillcrest

    San Diego, California, 92103

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • South Jordan Health Center

    South Jordan, Utah, 84009

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Moffitt Cancer Center-International Plaza

    Tampa, Florida, 33607

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • Smilow Cancer Hospital-Torrington Care Center

    Torrington, Connecticut, 06790

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • Smilow Cancer Hospital-Waterbury Care Center

    Waterbury, Connecticut, 06708

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare the progression free survival (PFS) between two study arms, i.e., olaparib monotherapy (arm 1) and olaparib + atezolizumab in combination (arm 2) based on normal Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with locally advanced or metastatic non-HER2-positive breast cancer harboring homologous deoxyribonucleic acid (DNA) repair (HDR) through BRCA 1/2 mutation.

SECONDARY OBJECTIVES:

  1. To compare the progression free survival (PFS) between the two study arms based on immune response criteria.

II. To compare the time to treatment failure (TTF) between the two study arms based on immune response criteria and normal RECIST.

III. To compare the overall response rate (ORR) between the two study arms based on immune response criteria and normal RECIST.

IV. To compare the duration of response (DoR) between the two study arms based on immune response criteria and normal RECIST.

  1. Determine the changes in extent of mutational burden in BRCA 1/2 mutated tumors at baseline and at progression.

VI. Evaluate and characterize changes in the extent of PD-L1 expression and tumor immune infiltrates.

VII. Retrospectively evaluate tumors with limited immune infiltrate (e.g. "non-inflamed") to determine if PARPi increased immune infiltration.

VIII. Determine the immune-related best overall response (irBOR) of olaparib in combination with atezolizumab in locally advanced or metastatic non-HER2+ breast cancer harboring HDR through BRCA 1/2 mutation.

EXPLORATORY OBJECTIVES:

  1. Evaluate changes in candidate neoantigen profiles and immune/inflammation signatures using DNA and ribonucleic acid (RNA)-sequencing in serial tumor biopsies.

II. Evaluate and characterize circulating tumor DNA (ctDNA) and immune parameters in blood.

III. Test the hypothesis that DNA repair status affects the tumor-immune interaction.

IV. Characterize mechanism of action of the PARP inhibitor olaparib. V. To explore the inclusion of patient reported symptomatic adverse events. VI. To use anti-Kynurenine antibodies for immunohistochemistry (IHC) as well as unbiased metabolome studies on plasma to understand the metabolic consequences of PARP-inhibition and their effects on immune infiltrates.

VII. To explore pharmacodynamic transcriptional changes induced by treatment in different immune cell populations and with high resolution in single cell RNA sequencing of peripheral blood mononuclear cell (PBMC) preparations. This will also be used to study changes in specific T-cell clonotypes.

VIII. To examine increased mitotic errors during response that are surveilled by the innate immune system.

IX. To test whether mutations or expression changes in genes tied to DNA repair regulation arise during acquired resistance and can be discerned by comparative genomics of pre- and at- progression biopsies.

  1. To examine whether biomarker development tied to mitotic errors will be of future utility in predicting PARPi response.

XI. To test DNA methylation relationship to resistance mechanism and RNA sequencing (seq).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive olaparib orally (PO) twice daily (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, computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan, and/or positron emission tomography (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: Patients receive olaparib as in Arm I and atezolizumab intravenously (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.

After completion of study treatment, patients are followed up at 30 days. Patients who come off treatment for reasons other than disease progression are followed every 4-8 weeks.

Being tested
Atezolizumab, Biopsy Procedure, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo a biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo a bone scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo a CT scan

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • OlaparibDrug

    Also called AZD 2281, AZD-2281, AZD2281, KU 0059436

    Given PO

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo a PET scan

  • Questionnaire AdministrationOther

    Ancillary studies

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs

    Undergo an x-ray

Study groups in NCT02849496
Study groupRoleWhat they receive
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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Olaparib; Procedure: Positron Emission Tomography; Other: Questionnaire Administration; Procedure: X-Ray Imaging
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.
Receives: Drug: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Olaparib; Procedure: Positron Emission Tomography; Other: Questionnaire Administration; Procedure: X-Ray Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Time measured from randomization, assessed up to 7 years

Secondary outcomes (2)

  1. Overall response rate (ORR)

    Evaluated by immune response criteria and normal Response Evaluation Criteria in Solid Tumors criteria. The ORR will be estimated using the 95% CI based on Wilson's method. The Fisher's exact test will be applied to examine the difference between two arms. The Wilcoxon rank sum test and Fisher's exact test will be applied to study the association between the response status and the continuous and categorical variables, respectively. The generalized non-linear model and logistic regression will be applied for multivariable data analysis. The adjusted p-value and 95% CI of the odds ratios (OR) will be reported.

    Measured: Up to 7 years

  2. Duration of response (DoR)

    The study arms will be compared for duration of response survival with Kaplan-Meier estimates and log-rank tests. The Rothman 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 DoR data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.

    Measured: Time from documentation of tumor response to disease progression, assessed up to 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2016 (estimated)
  2. Study start30 Mar 2017
  3. Primary completion10 Jun 2026
  4. Study completion26 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02849496
Sponsor's protocol ID
NCI-2016-01130
Other IDs
NCI-2016-01130, 1608018258, 10020, 10020, UM1CA186644, UM1CA186686, UM1CA186688, UM1CA186689
Status last verified
Aug 2026
First submitted
27 Jul 2016
Last updated
28 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Biopsy Procedure and Biospecimen Collection in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by National Cancer Institute (NCI) at 58 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: Time measured from randomization, assessed up to 7 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02849496.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.

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