An International Multicenter Phase II Trial of Durvalumab (MEDI4736) Plus OLAparib Plus Fulvestrant in Metastatic or Locally Advanced ER-positive, HER2-negative Breast Cancer Patients Selected Using Criteria That Predict Sensitivity to Olaparib

UNICANCER2 sites in 1 country172 target enrollmentAugust 26, 2019

ConditionsER-positive and HER2-negative Metastatic or Locally Advanced Breast Cancer a Germline or Somatic BRCA Mutation, or a Deleterious Alteration of Other Genes Involved in Homologous Recombination Repair (HRR) or in MSI Status

InterventionsDurvalumab Olaparib Fulvestrant

DrugsDurvalumab Olaparib Fulvestrant

Overview

Phase: Phase 2
Intervention: Durvalumab
Conditions: ER-positive and HER2-negative Metastatic or Locally Advanced Breast Cancer
Sponsor: UNICANCER
Enrollment: 172
Locations: 2
Primary Endpoint: Progression-free survival rate (PFSR)
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study evaluates the efficacy of the combination of olaparib, durvalumab, and fulvestrant for the treatment of patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer with BRCA gene alterations or alterations of genes involved in homologous recombination repair (HRR) or microsatellite instability (MSI) status.

Registry

clinicaltrials.gov

Start Date

August 26, 2019

End Date

August 2027

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

UNICANCER

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed ER-positive (≥10%), HER2-negative (0, 1+, 2+, and no HER2 gene amplification by ISH), metastatic or locally advanced breast cancer that is not amenable to resection or radiation with curative intent.
•Patients aged ≥18 years old (post-menopausal or pre/per-menopausal women and men).
•Documented personal germline alteration in BRCA1 or BRCA2 that is predicted to be deleterious. Testing may be performed at any time prior to inclusion.
•OR Deleterious germline or somatic alterations implicated in the HRR pathway (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCA, FAND2, FANCL, MRE11A, NBN, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D and RAD54L) or in MSI status all based on central tumor next generation DNA sequencing performed at screening visit.
•A tumor biopsy sample must be available: if obtaining an adequate metastatic tumor biopsy is impossible (including bone metastasis), analyses will be done on a biopsy from the primary breast tumor.
•Patients with a life expectancy ≥16 weeks.
•ECOG performance status 0-
•At least one evaluable lesion, either measurable or non-measurable that can be accurately assessed at baseline by CT-scan or MRI by RECIST v1.
•Patients could have received 1 line of endocrine therapy (including CDK4/6 inhibitor, but excluding fulvestrant or mTOR inhibitor) and/or 1 line of chemotherapy in the metastatic setting.
•Within 28 days prior to administration of study treatment, patients must have adequate organ and bone marrow functions:

Exclusion Criteria

•Patients without olaparib targetable genomic anomaly identified during the screening phase.
•Gene variants (class 1, 2, and 3) of unknown significant prognostic for olaparib sensitivity.
•Patients with history of other malignancy except non-melanoma skin cancer, in-situ cancer of the cervix, or solid tumors including lymphomas (without bone marrow involvement) curatively treated and with no evidence of disease for ≥5 years prior to study entry.
•Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome/acute myeloid leukemia.
•Patients with symptomatic uncontrolled brain metastases. In addition, treatment of the central nervous system disease must have finished (whole brain radiation, radiosurgery) at least 2 weeks before Cycle 1 Day
•Patients must not require \>10 mg of prednisone per day or an equivalent dose of other corticosteroids.
•Prior treatment with a PARP inhibitor (including olaparib) and/or PD-1 or PD-L1 inhibitor (including durvalumab).
•Patients having received anticancer chemotherapy or any other investigational therapy within 3 weeks prior of the study. Endocrine therapy must have been discontinued 7 or more days before Cycle 1 Day
•Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day
•Biphosphonates and denosumab are allowed.

Arms & Interventions

Study Arm

Intervention: Durvalumab

Study Arm

Intervention: Olaparib

Study Arm

Intervention: Fulvestrant

Outcomes

Primary Outcomes

Progression-free survival rate (PFSR)

Time Frame: 24 weeks

The progression-free survival rate at 24 weeks defined as the percentage of patients alive without disease progression at 24 weeks after inclusion. PFSR will be evaluated by local investigator using Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1). The death of a patient for any cause within 24 weeks will be considered as failure