Olaparib In Metastatic Breast Cancer

Running, not enrolling · Phase 2

Conditions studied: Metastatic Breast Cancer, Invasive Breast Cancer, Somatic Mutation Breast Cancer (BRCA1), Somatic Mutation Breast Cancer (BRCA2), CHEK2 Gene Mutation, ATM Gene Mutation, PALB2 Gene Mutation, RAD51 Gene Mutation, BRIP1 Gene Mutation, NBN Gene Mutation

In brief

This research study is for patients with metastatic breast cancer. * Metastatic means that the cancer has spread beyond the breast. In addition, through genetic testing of the blood or tumor, an altered gene has been found that suggests the tumor may not be able to repair its genetic material (DNA) when it becomes damaged. * This aspect of the cancer may cause it to be more sensitive - that is, more effectively killed by certain types of drugs such as the study agent being evaluated in this trial, Olaparib. * Olaparib is a type of drug known as a PARP inhibitor. Some types of breast cancer and ovarian cancer share some basic features that make them sensitive to similar treatments. Information from those other research studies suggests that this drug may help to treat metastatic breast cancer. * This study will evaluate whether olaparib is effective in breast cancer patients whose tumor has a mutation in one of the other genes that function with BRCA1 and BRCA2 to repair damaged DNA .This mutation may have been inherited from a parent, or may have developed only in the tumor. * This study will also evaluate whether olaparib is effective in breast cancer patients whose tumor has a mutation in BRCA1 or BRCA2 that was acquired by the tumor, but not inherited.

Key facts

Study ID

NCT03344965

Run by

Beth Israel Deaconess Medical Center

People needed

114

Starts

2018-04-01

Expected to finish

2026-06-30

Last updated by the study team

2026-01-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically confirmed invasive breast cancer with stage IV disease, either biopsy proven or with unequivocal evidence of metastatic disease by physical examination or radiological study.
• Cohorts 1 and 2: Documented germline (Cohort 1) or somatic mutation or homozygous deletion (Cohort 2) in one of the DNA repair genes listed below that is deleterious or suspected to be deleterious, and no germline BRCA1 or BRCA2 mutation. The mutation may be identified through any CLIA approved NGS panel.
• ATM, ATR, BARD1, BRIP1 (FANCJ), CHEK2 , FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN, PALB2, RAD50, RAD51C, RAD51D, plus other HR-related genes at the discretion of Dr. Tung with the key study collaborators (see details below in italics). (Cohorts 1 or 2)
• -- OR
• Documented somatic mutation (deleterious or suspected deleterious) in BRCA1 or BRCA2 through any CLIA approved lab only if in addition to the lack of a germline BRCA1/2 mutation is demonstrated through a CLIA approved lab. Patients with germline mutations in BRCA1/2 are NOT eligible for this study. (Cohort 2 only)
• Cohort 1a: germline PALB2 mutation
• - The mutation must be identified through a CLIA-approved NGS panel. Mutations must be reviewed and confirmed by Dr. Tung to meet eligibility prior to registration.
• Cohort 2a: somatic mutation of BRCA 1 or BRCA 2
• - The mutation must be identified through a CLIA-approved NGS panel. Mutations must be reviewed and confirmed by Dr. Tung to meet eligibility prior to registration. Documentation of absence of germline mutation in BRCA 1/2 is required.
• All deep (homozygous) deletions, frameshift mutations and truncating mutations in the genes listed above are eligible as well as missense variants in these genes that have previously been reported as pathogenic or likely pathogenic. If there is a discrepancy between two labs regarding the pathogenicity of a particular variant, the final decision regarding eligibility will be determined by the study steering committee.
• At least one measurable lesion that can be accurately assessed at baseline by CT (MRI where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1.
• - NOTE: If the only site of measurable of disease has been previously irradiated, there must be evidence of post-radiation progression. For a lesion to be considered as measurable, it must be one that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements
• Patients may not have progressed on more than two chemotherapy regimens in the metastatic setting.
• The following will NOT be counted as a prior line of cytotoxic chemotherapy:
• If a patient discontinued a cytotoxic regimen due to toxicity (e.g., hypersensitivity or neuropathy) but had not progressed on that regimen, or if a prior chemotherapy regimen was discontinued after response achieved, it will not be counted in the number of prior chemotherapy regimens allowed.
• Prior hormonal therapy and non-hormonal targeted therapy; including the combination of an aromatase inhibitor and everolimus.
• Targeted and biologic therapies.
• The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as this was started at least 5 days prior to study treatment.
• The most recent cytotoxic, biologic or targeted therapy received must have been completed at least 21 days prior to study treatment; hormonal therapy must have been completed at least 7 days prior, unless otherwise noted.
• Prior therapy is allowed as follows:
• Platinum chemotherapy in the adjuvant setting is allowed, if the last platinum dose was > 12 months before identification of metastatic disease. Platinum-based chemotherapy in the metastatic setting is not permitted.
• History of prior anthracycline (e.g. doxorubicin, epirubicin) and taxane-based (e.g. paclitaxel, docetaxel) chemotherapy in the neo-adjuvant / adjuvant or metastatic setting is preferred, but not required.
• Patients with hormone receptor-positive (estrogen and/or progesterone receptor-positive) disease must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy. Endocrine therapy must have been completed at least 7 days before study treatment.
• Prior radiation is allowed; radiation therapy must have been completed at least 21 days before study treatment.
• Prior treatment with FDA approved or investigational biologics (other than PARP inhibitors) and novel molecularly targeted therapies, including oral or IV formulations, shall not exclude patients from participation.

You may not qualify if…

• Any previous treatment with a PARP inhibitor, including olaparib.
• Germline BRCA1 or BRCA2 mutation
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) and grapefruit, grapefruit juice or any product containing grapefruit,or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• 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.
• 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, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
• Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy, excluding alopecia
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Patients with prior myelodysplastic syndrome or acute myeloid leukemia.
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer; curatively treated in situ cancer of the cervix; ductal carcinoma in situ (DCIS); Stage 1, grade 1 endometrial carcinoma; or, other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years
• Resting EKG with QTc > 470 msec or family history of long QT syndrome. If EKG demonstrates QTc >470 msec, patient will be eligible only if repeat EKG demonstrates QTc ≤470 msec.
• Pregnant or breast feeding women.
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
• Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
• Patients with known active hepatitis (i.e., Hepatitis B or C)
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable).
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication

Where it is running

• University of Alabama at Birmingham — Birmingham, Alabama, United States
• University of California, San Francisco — San Francisco, California, United States
• University of Chicago — Chicago, Illinois, United States
• Indiana University — Indianapolis, Indiana, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Brigham and Women's Hospital — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Memorial Sloan Kettering Cancer Center Basking Ridge — Basking Ridge, New Jersey, United States
• Memorial Sloan Kettering Cancer Center Monmouth — Middletown, New Jersey, United States
• Memorial Sloan Kettering Cancer Center Bergen — Montvale, New Jersey, United States
• Memorial Sloan Kettering Cancer Center Commack — Commack, New York, United States
• Memorial Sloan Kettering Cancer Center Westchester — East White Plains, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Memorial Sloan Kettering Cancer Center Nassau — Uniondale, New York, United States
• Duke University — Durham, North Carolina, United States
• UPMC Hillman Cancer Center - Erie — Erie, Pennsylvania, United States
• University of Pennsylvania — Philadelphia, Pennsylvania, United States
• University of Pittsburgh — Pittsburgh, Pennsylvania, United States
• University of Washington Fred Hutchinson Cancer Care — Seattle, Washington, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.