Phase II Multicenter Study of Durvalumab and Olaparib in Platinum tReated Advanced Triple Negative Breast Cancer (DORA)

NCT03167619 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pro00080769
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, international, multicenter, Phase II study designed to explore the efficacy of olaparib or olaparib in combination with durvalumab in platinum-treated mTNBC. The primary objectives are to explore olaparib or olaparib in combination with durvalumab as maintenance therapy following clinical benefit with platinum-based therapy in subjects with mTNBC.

Conditions

Triple Negative Breast Cancer

Keywords

Metastatic; Platinum Sensitive; Advanced; PARP inhibitor

Outcome Measures

Primary Outcomes (2)

• Efficacy of Olaparib Alone as Assessed by PFS (Progression-free Survival) Reported as Events Per Month

  PFS, defined as the time from randomization to the first occurrence of disease progression or death from any cause on study for olaparib alone. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Death on study is defined as death from any cause within 30 days of the last dose of study treatment regimen. Reported as events (disease progression or death) per month.

  From date of randomization until the date of documented progression or date of death, whichever came first, approximately 1 year.

• Efficacy of Olaparib in Combination With Durvalumab as Assessed by PFS (Progression-free Survival)

  PFS, as defined as the time from randomization to the first occurrence of disease progression (as determined using RECIST v1.1 criteria and assessed by the investigator) or death from any cause on study for olaparib in combination with durvalumab. Death on study is defined as death from any cause within 30 days of the last dose of study treatment regimen. Reported as (disease progression or death) events per month.

  From date of randomization until the date of documented progression or date of death, whichever came first, approximately 1 year.

Secondary Outcomes (6)

• Overall Survival (Olaparib Alone)

  From date of randomization until death or last patient contact, approximately 2 years

• Overall Survival (Olaparib in Combination With Durvalumab)

  From date of randomization until death or last patient contact, approximately 2 years

• Overall Response Rate (ORR) as Measured by Number of Participants Achieving Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1 (Olaparib Alone)

  Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year

• Overall Response Rate (ORR) as Measured by Number of Participants Achieving Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1 (Olaparib in Combination With Durvalumab)

  Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year

• Clinical Benefit Rate (CBR) as Measured by the Number of Participants Achieving Complete Response (CR), Partial Response (PR) or Stable Disease for ≥ 24 Weeks (SD) as Defined by RECIST 1.1. (Olaparib Alone)

  Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year

Study Arms (2)

A - olaparib alone

EXPERIMENTAL

Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Drug: Olaparib Oral Product

B - olaparib plus durvalumab

EXPERIMENTAL

Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Drug: Olaparib Oral Product in combination with Durvalumab

Interventions

Olaparib Oral Product DRUG

olaparib 300mg twice daily

A - olaparib alone

Olaparib Oral Product in combination with Durvalumab DRUG

olaparib 300mg twice daily plus intravenous durvalumab every 28 days

B - olaparib plus durvalumab

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 21 years of age
• ECOG performance status 0-2
• Inoperable locally advanced or metastatic breast cancer not amenable to resection with curative intent and histologically confirmed to be estrogen receptor (ER) negative, progesterone receptor (PR) negative, and HER2 negative:
• ER negative status is defined as \< 1% tumor cells positive for ER by immunohistochemistry (IHC), irrespective of staining intensity
• PR negative status is defined as \< 1% tumor cells positive for PR by IHC, irrespective of staining intensity
• NOTE: Enrollment is permitted for ER/PR low-expression subjects (defined as ≤ 10%) who are expected to benefit from this trial at the investigator's discretion.
• HER2 negative status is determined by:
• IHC 1+, as defined by incomplete membrane staining that is faint/barely perceptible and within \> 10% of invasive tumor cells, or
• IHC 0, as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within ≤ 10% of the invasive tumor cells, or
• FISH negative based on:
• Single-probe average HER2 copy number \< 4.0 signals / cell, or
• Dual-probe HER2/CEP17 ratio \< 2.0 with an average HER2 copy number \< 4.0 signals / cell
• Minimum six 1-weekly doses or three 3-weekly doses of platinum chemotherapy (monotherapy or combination therapy at investigator's discretion) with stable disease (SD), partial response (PR) or complete response (CR) to the platinum therapy as assessed by investigator.
• Has received no more than 2 prior chemotherapy regimens for metastatic breast cancer including current platinum based chemotherapy.
• Able to provide a representative formalin-fixed, paraffin embedded tumour specimen archival or fresh tissue for correlative studies and biomarker analysis.

You may not qualify if:

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of first dose of treatment. Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device.
• Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
• Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, or similar treatment) is not considered a form of systemic treatment.
• Is taking chronic systemic steroids in doses \> 10mg of prednisolone or equivalent within 7 days prior to the first dose of trial treatment.
• Previous treatment with PARP inhibitors including olaparib.
• Patients that have required discontinuation of treatment due to treatment-related toxicities from prior therapy with PD-1, PDL-1 or CTLA-4 inhibitors or previous history of immune-related grade 3 or 4 adverse event.
• Known active central nervous system metastasis and / or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they have:
• Stable brain metastases \[without evidence of progression by imaging (confirmed by computerized tomography {CT} scan if CT used at prior imaging) for at least four weeks prior to the first dose of trial treatment\*\*,
• No evidence of new or enlarging brain metastases; any neurologic symptoms should have returned to baseline,
• Not used steroids for brain metastases in the 7 days prior to trial initiation. Taking chronic systemic steroids in doses ≤ 10mg of prednisolone is allowed.
• This exception does not include carcinomatous meningitis, as subjects with carcinomatous meningitis are excluded regardless of clinical stability.
• History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan.
• Patients with suspected or confirmed myelodysplastic syndrome/acute myeloid leukemia.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence.

Sponsors & Collaborators

• Duke University: lead
• AstraZeneca: collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27705, United States

Location

Related Publications (1)

• Tan TJ, Sammons S, Im YH, She L, Mundy K, Bigelow R, Traina TA, Anders C, Yeong J, Renzulli E, Kim SB, Dent R. Phase II DORA Study of Olaparib with or without Durvalumab as a Chemotherapy-Free Maintenance Strategy in Platinum-Pretreated Advanced Triple-Negative Breast Cancer. Clin Cancer Res. 2024 Apr 1;30(7):1240-1247. doi: 10.1158/1078-0432.CCR-23-2513.

  PMID: 38236575 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Biostatistician
• Organization: Duke Clinical Research Institute

lilin.she@duke.edu

919-668-8052

Study Officials

• Sarah Sammons, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 30, 2017
• Study Start: October 4, 2018
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2022
• Last Updated: September 13, 2022
• Results First Posted: September 13, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)