Olaparib Maintenance Therapy in Metastatic Breast Cancer

NCT05629429 | Unknown Phase 2

• 1 other identifier: 202202045MIPA
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

Brief Summary

Olaparib, a PARP inhibitor, is proven as an effective therapy for germline BRCA1/2-mutated breast cancer; however, the therapeutic efficacy for somatic mutation in BRCA1/2 or genes of homologous recombination DNA repair is unclear. Maintenance of Oalaprib can delay the disease progression in patients with BRCA1/2 mutated advanced ovarian cancer after treatment with platinum based chemotherapy. The investigators design a phase 2 study to evaluate the efficacy of maintenance of Olaparib in patients with metastatic breast cancer. The investigators enroll patients with metastatic ER(+)Her2(-) or triple-negative breast cancer. Patients who are chemotherapy-naïve or prior 1-line chemotherapy are eligible for screening. All eligible patients will receive 4 cycles of platinum based chemotherapy. Gene test will be performed on their breast tumor. If patients have mutation of HR genes and at least stable disease after platinum based chemotherapy, they will be randomized to treatment arm (Olaparib maintenance) or control arm (continuation of chemotherapy). The primary end-point is progression-free survival, and the secondary end-point is to assess the response rate, overall survival and quality of life.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• CT or MRI assessment

  Progression-free survival

  3 years

Secondary Outcomes (3)

• Survive or death

  3 years

• CT or MRI assessment

  3 years

• Questionnaire

  3 years

Study Arms (2)

Arm 1: olaparib treatment

EXPERIMENTAL

Olaparib 300mg BID PO

Drug: Olaparib

Arm2: continuation of the chemotherapy

ACTIVE COMPARATOR

continuation of the current platinum based chemotherapy

Drug: Chemotherapy drug

Interventions

Olaparib DRUG

Olaparib 300mg BID PO

Arm 1: olaparib treatment

Chemotherapy drug DRUG

Continue platinum based chemotherapy

Arm2: continuation of the chemotherapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a life expectancy ≥ 16 weeks.
• Provision of informed consent prior to any study specific procedures
• years of age or older; gender includes female and male
• ECOG 0-1
• Patients should be diagnosed as metastatic breast cancer ER(+)Her2(-) or TNBC, diagnosis could be by local hospital
• HER2 negative \[IHC 0, 1+ or IHC 2+ with corresponding ISH non-amplified of ratio less than 2.0 or ISH nonamplified ratio less than 2.0\] as per ASCO-CAP HER2 guideline recommendations 2013 (ASCO-CAP).
• At least one lesion, not previously irradiated, 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)
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined at least one of the followings: (a) Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments; (b) Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50; (c) radiation- induced oophorectomy with last menses \>1 year ago; (d) chemotherapy-induced menopause with \>1 year interval since last menses; (f) surgical sterilisation (bilateral oophorectomy or hysterectomy)
• Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception (\[see appendix H for acceptable methods\]) if they are of childbearing potential
• No more than previous 0-1 line of chemotherapy after metastasis confirmed
• For ER(+) breast cancer, patients should fail at least 1-line of hormone therapy (either in adjuvant setting or in metastatic cancer) before entering this study
• Patients should undergo 4-cycles of platinum-based chemotherapy and have a CR, PS or SD prior to randomisation.
• At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging \[MRI\] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1.
• Patients must have normal organ and bone marrow function measured within 28 days prior to randomisation as defined below:
• Haemoglobin (Hb) ≥10.0 g/dL

You may not qualify if:

• Cytotoxic chemotherapy, hormonal or non hormonal targeted therapy within 21 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 21 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 5 days prior to study treatment.
• More than 2 prior lines of cytotoxic chemotherapy for metastatic disease.
• Prior treatments with hormonal therapy and non hormonal targeted therapy are allowed and not counted as a prior line of cytotoxic chemotherapy.
• For the purposes of this protocol, the combination of "an aromatase inhibitor and everolimus" or "a hormonal therapy and CDK4/6 inhibitor" is not considered cytotoxic chemotherapy.
• Treatment with biologics will not be considered as prior line of therapy.
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• Previous treatment with a PARP inhibitor (including olaparib)
• The minimum washout period for immune checkpoint blockade therapy shall be 21 days.
• Patients with MDS/AML or with features suggestive of MDS/AML.
• Patients with second primary cancer, EXCEPTIONS: 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 tumours curatively treated with no evidence of disease for ≥ 5 years prior to study entry (including lymphomas \[without bone marrow involvement\]).
• Mean resting corrected QTc interval using the Fridericia formula (QTcF) \>470 msec/female patients and \>450 msec for male patients (as calculated per institutional standards) obtained from 3 ECGs performed 2-5 minutes apart at study entry, or congenital long QT syndrome.
• Any of the following cardiac diseases currently or within the last 6 months
• Unstable angina pectoris
• Congestive heart failure ≥ Class 2 as defined by the New York Heart Association
• Acute myocardial infarction

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• AstraZeneca: collaborator

Study Sites (3)

National Taiwan University Hospital

Taipei, Please Select, 100, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, Please Select, Taiwan

NOT YET RECRUITING

National Taiwan University Hospital Yunlin branch

Yuanlin, Taiwan

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Po-Han Lin

CONTACT

886972653807; pohanlin01@gmail.com

Yu-Ting Chiu

CONTACT

886981020813; candy987466@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: November 29, 2022
• Study Start: February 7, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 17, 2024

Record last verified: 2024-01

Locations

TW (3)