Olaparib In Metastatic Breast Cancer

NCT03344965 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 17-428
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 20

Brief Summary

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.

Conditions

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

Keywords

Metastatic Breast Cancer; Invasive Breast Cancer; Somatic Mutation Breast Cancer (BRCA1); Somatic Mutation Breast Cancer (BRCA2)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  RECIST 1.1 criteria will be reported with a two-sided 90% confidence interval using the method from Atkinson and Brown to account for the two-stage design

  21 Days

Secondary Outcomes (5)

• Clinical Benefit Rate

  16 weeks

• Progression Free Survival

  36 Months

• Stable Disease

  36 Months

• Number of Participants with Severe Adverse Events

  after the first dose of study treatment and ends 30 days following the last administration of study treatment or study discontinuation/termination,

• Mutant Allele Frequency

  36 months

Study Arms (4)

OLAPARIB QD GERMLINE MUTATION

EXPERIMENTAL

After the screening procedures confirm eligibility to participate in the research study: * Olaparib: Each study treatment cycle lasts 21 days (3 weeks), taking 2 times per day, 12 hours apart. * Tumor measurement q6 weeks x 24 weeks, then q 12 weeks

Drug: Olaparib

OLAPARIB QD GERMLINE MUTATION - EXPANSION

EXPERIMENTAL

After the screening procedures confirm eligibility to participate in the research study: * Olaparib: Each study treatment cycle lasts 21 days (3 weeks), taking 2 times per day, 12 hours apart. * Tumor measurement q6 weeks x 24 weeks, then q 12 weeks

Drug: Olaparib

OLAPARIB QD SOMATIC MUTATION

EXPERIMENTAL

After the screening procedures confirm eligibility to participate in the research study: * Olaparib: Each study treatment cycle lasts 21 days (3 weeks), taking 2 times per day, 12 hours apart. * Tumor measurements q6 weeks x 24 weeks, then q 12 weeks

Drug: Olaparib

OLAPARIB QD SOMATIC MUTATION - EXPANSION

EXPERIMENTAL

After the screening procedures confirm eligibility to participate in the research study: * Olaparib: Each study treatment cycle lasts 21 days (3 weeks), taking 2 times per day, 12 hours apart. * Tumor measurements q6 weeks x 24 weeks, then q 12 weeks

Drug: Olaparib

Interventions

Olaparib DRUG

olaparib tablets bid daily continuously on a 21 day cycle until progression, intolerable toxicity, consent withdrawn, patient noncompliance or death.

Also known as: AZD2281, KU-0059436

OLAPARIB QD GERMLINE MUTATION; OLAPARIB QD GERMLINE MUTATION - EXPANSION; OLAPARIB QD SOMATIC MUTATION; OLAPARIB QD SOMATIC MUTATION - EXPANSION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Johns Hopkins University: collaborator
• AstraZeneca: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21218, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center Westchester

East White Plains, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center Nassau

Uniondale, New York, 11553, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

UPMC Hillman Cancer Center - Erie

Erie, Pennsylvania, 16505, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

University of Washington Fred Hutchinson Cancer Care

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• Tung NM, Robson ME, Li T, Nanda R, Shah PD, Khoury K, Kimmick G, Santa-Maria C, Brufsky A, DeMeo M, Vieira JP, Carey LA, Wulf G, Domchek S, Krop IE, Wolff AC, Winer EP, Garber JE; Translational Breast Cancer Research Consortium (TBCRC). TBCRC 048 (Olaparib Expanded) Expansion Cohorts: Phase II Study of Olaparib Monotherapy for Patients With Metastatic Breast Cancer With Germline Mutations in PALB2 or Somatic Mutations in BRCA1 or BRCA2. J Clin Oncol. 2026 Mar 10;44(8):653-661. doi: 10.1200/JCO-25-02075. Epub 2026 Jan 28.

  PMID: 41604601 DERIVED

• Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. J Clin Oncol. 2020 Dec 20;38(36):4274-4282. doi: 10.1200/JCO.20.02151. Epub 2020 Oct 29.

  PMID: 33119476 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Fanconi Anemia, Complementation Group D1

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Nadine Tung, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 17, 2017
• Study Start: April 1, 2018
• Primary Completion: July 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)