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Triple Negative Breast CancerPhase 2DORANCT03167619

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

A Phase 2 study testing Olaparib Oral Product and Olaparib Oral Product in combination with Durvalumab in people with Triple Negative Breast Cancer, run by Duke University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 21 years and older, women only
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
Olaparib Oral Product and Olaparib Oral Product in combination with Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
4 Oct 2018to 30 Jun 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Hemoglobin ≥ 9.0 g/dL and no blood transfusions in the 28 days prior to study entry. Absolute neutrophil count ≥1,500/mm3. Platelet count ≥100 x 10^9/L.
  • Total bilirubin <1.5 x the upper limit of normal (ULN) with the following exception: subjects with known Gilbert's disease who have serum bilirubin <3 x ULN may be enrolled.
  • Aspartate transaminase (AST) and alanine transaminase (ALT) <2.5 x ULN with the following exceptions: subjects with documented liver or bone metastases may have AST and ALT <5 x ULN.
  • Alkaline phosphatase (ALP) <2 x ULN (<5 x ULN in subjects with known liver involvement and <7 ULN in subjects with known bone involvement).
  • Serum creatinine <1.5 x ULN or creatinine clearance >51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
  • For subjects of childbearing potential, agreement (by both subject and partner) to use two effective forms of contraception, including surgical sterilization, reliable barrier method, birth control pills, contraceptive hormone implants, or true abstinence and to continue its use for the duration of the study and for 3 months after last dose of study treatment.
  • Subjects of childbearing potential should have a negative urine or serum pregnancy test during their screening visit. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Subjects willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examination.
  • For inclusion in genetic research, subjects must provide informed consent for genetic research collection of specimens to be stored at repository for future research.

Who cannot join

  • 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.
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  • 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.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ.
  • Major surgery within 2 weeks of starting the study, and subjects must have recovered from any effects of any major surgery.
  • Receipt of radiation therapy within 4 weeks prior to starting study drug(s). Limited field of radiation for palliation within 2 weeks of the first dose of study treatment is allowed provided:
  • The lung is not in the radiation field
  • Irradiated lesion(s) cannot be used as target lesions
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, active bleeding diatheses including any subjects known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness / social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
  • Subjects unable to swallow orally administered medication, and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Subjects requiring treatment with potent inhibitors or inducers of CYP3A4.
  • Pregnant or breast-feeding women. If breastfeeding can be stopped prior to study enrollment until 1 month after the last study dose, then the patient could be allowed to enter the study.
  • Immunodeficient subjects, eg, subjects who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Received a live vaccine within 30 days of planned start of study therapy.
  • Subjects with a known hypersensitivity to olaparib or durvalumab, or any of the excipients of the product.
  • Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
  • History of allogeneic organ transplant
  • Active bleeding diatheses
  • Patients with known active hepatic disease (ie, Hepatitis B or C)
  • Known history of previous clinical diagnosis of tuberculosis.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University

    Durham, North Carolina, 27705

Other trials in United States

About this study

Official title: Phase II Multicenter Study of Durvalumab and Olaparib in Platinum tReated Advanced Triple Negative Breast Cancer

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.

Read the detailed description

Subjects suitable for enrollment into this trial are adult subjects with histologically documented triple negative adenocarcinoma of the breast that is inoperable, locally advanced, or metastatic, and is not amenable to resection with curative intent, and who have received at least 4 cycles of platinum-based chemotherapy in the 1st or 2nd line setting AND derived clinical benefit (CR / PR / SD) per RECIST 1.1 with platinum-based therapy as determined by the treating physician.

Eligible subjects will be randomized to either olaparib or olaparib in combination with durvalumab. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Upon treatment discontinuation, subjects will be followed every 2 months for survival.

Although randomization will be used to allocate subjects to either the olaparib or olaparib in combination with durvalumab arm, no comparisons between treatment regimens are planned. The purpose of randomization was to reduce bias due to subject selection into either treatment arm.

Being tested
Olaparib Oral Product, Olaparib Oral Product in combination with Durvalumab
Keywords
Metastatic, Platinum Sensitive, Advanced, PARP inhibitor
Medical subject headings
Triple Negative Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Olaparib Oral ProductDrug

    olaparib 300mg twice daily

  • Olaparib Oral Product in combination with DurvalumabDrug

    olaparib 300mg twice daily plus intravenous durvalumab every 28 days

Study groups in NCT03167619
Study groupRoleWhat they receive
A - olaparib aloneExperimentalTwice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Receives: Drug: Olaparib Oral Product
B - olaparib plus durvalumabExperimentalTwice 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.
Receives: Drug: Olaparib Oral Product in combination with Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (6)

  1. Overall Survival (Olaparib Alone)

    To determine the efficacy of maintenance olaparib following platinum based chemotherapy as assessed by overall survival (OS).

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

  2. Overall Survival (Olaparib in Combination With Durvalumab)

    To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum based chemotherapy as assessed by overall survival (OS).

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

  3. 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)

    To determine the efficacy of maintenance olaparib following platinum-based chemotherapy as assessed by overall response rate (ORR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

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

  4. 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)

    To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum-based chemotherapy as assessed by overall response rate (ORR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

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

  5. 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)

    To determine the efficacy of maintenance olaparib following platinum-based chemotherapy as assessed by clinical benefit rate (CBR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD); Clinical Benefit (CB) = CR + PR + SD for >= 24 weeks.

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

  6. 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 in Combination With Durvalumab)

    To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum-based chemotherapy as assessed by clinical benefit rate (CBR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD); Clinical Benefit (CB) = CR + PR + SD for >= 24 weeks.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2017
  2. Study start4 Oct 2018
  3. Primary completion30 Jun 2021
  4. Study completion30 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03167619
Sponsor's protocol ID
Pro00080769
Acronym
DORA
Status last verified
Jun 2022
First submitted
23 May 2017
Last updated
13 Sep 2022
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38236575

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaparib Oral Product and Olaparib Oral Product in combination with Durvalumab in people with Triple Negative Breast Cancer, run by Duke University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of Olaparib Alone as Assessed by PFS (Progression-free Survival) Reported as Events Per Month (time frame: From date of randomization until the date of documented progression or date of death, whichever came first, approximately 1 year.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03167619, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2022.

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