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Breast CancerPhase 2NOBROLANCT03367689

A Two-stage Simon Design Phase II Study for Non-BRCA MBC Patients With HRD Treated With Olaparib Single Agent

A Phase 2 study testing Olaparib in people with Breast Cancer, run by MedSIR at 5 sites in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an international, multi-centre, non-controlled, open-label, single arm, two-stage Simon Design phase II study for non-BRCA metastatic breast cancer (MBC) patients with homologous recombination deficiency treated with Olaparib single agent. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Olaparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
5 sitesSpain
Study dates
17 Apr 2018to 31 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

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

Who may be able to join

  • Patients are eligible for inclusion only if they meet ALL the following criteria:
  • Female patients ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) score lower or equal to 1.
  • Life expectancy greater or equal to 16 weeks.
  • Confirmed TN locally advanced or metastatic breast cancer in the first stage. For the second stage, luminal-like patients (RH-positive HER2-negative) will be allowed.
  • Wild type BRCA1 and BRCA2 (germline). Variants with unknown significance are eligible.
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  • Tumors must exhibit a HRD signature according to Foundation Medicine's Foundation One assay. Formalin fixed, paraffin embedded (FFPE) tumor sample from the metastatic cancer must be available for central testing. If there is not written confirmation of the availability of an archived tumor sample prior to enrolment the patient is not eligible for the study.
  • No more than three (and at least one) previous lines for the metastatic disease. Previous treatment must include taxanes (neo/adjuvant scenario is also possible) if not formally contraindicated.
  • Patient must have measurable disease according to RECIST 1.1 criteria. 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 > or equal 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
  • Patients must have normal organ and bone marrow function measured within 35 days prior to administration of study treatment as defined below:
  • Hematological: White blood cell (WBC) count >3.0 x 109/L, absolute neutrophil count (ANC) > or equal 1.5 x 109/L, platelet count ≥100.0 x109/L, and hemoglobin >10.0 g/dL (>6.2 mmol/L) with no blood transfusion in the past 35 days.
  • Hepatic: bilirubin ≤ 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) < or equal 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be < or equal 5x ULN.
  • Renal: creatinine clearance estimated using the Cockcroft-Gault equation of > or equal 51 mL/min
  • Patient has been informed about the nature of study, and has agreed to participate, and signed the Informed Consent form (ICF) prior to participation in any study-related activities
  • No other malignancies within the past five years except adequate treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCICTCAE version 4.03 Grade < or equal 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days prior to administration of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments; Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50; Radiation-induced oophorectomy with last menses >1 year ago; Chemotherapy-induced menopause with >1 year interval since last menses; Surgical sterilization (bilateral oophorectomy or hysterectomy).

Who cannot join

  • Patients will be excluded from the study if they meet ANY of the following criteria:
  • RH-positive (based on local laboratory results) or unknown for the first stage. In the second stage, luminal-like HER2-negative patients will be allowed.
  • HER2-positive (based on local laboratory results [performed by immunohistochemistry/fluorescence in situ hybridization (FISH)] or unknown.
  • Locally advanced breast cancer candidate for a radical treatment.
  • Has deleterious germline BRCA1 or BRCA2 mutation as determined by local test.
  • Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 35 days.
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  • Patients with symptomatic visceral disease are not eligible.
  • 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.
  • Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
  • Have had a major surgery (defined as requiring general anesthesia) or significant traumatic injury within 2 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study.
  • Resting ECG with QTc > 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome.
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
  • Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors. The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong or moderate CYP3A inducers. 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.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Patients with known active hepatitis (i.e. Hepatitis B or C).
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
  • Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable, for timing refer to inclusion criteria no.9).
  • Are unable to swallow orally administered medication.
  • Patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent (excluding inhaled steroids), except for prophylaxis use.
  • Female patients who are pregnant or breastfeeding, or adults of reproductive potential who are not using effective birth control methods.
  • Patients unwilling to or unable to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  • Patients that have previously receive any PARP inhibitor for any reason, including olaparib.
  • Known hypersensitivity to olaparib excipients or any of the excipients of the product.
  • Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site).
  • Previous enrolment in the present study.
  • Participation in another clinical study with an investigational product during the last 3 weeks.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Spain5 sites

  • Hospital del Mar

    Barcelona

  • Onkologikoa

    Donostia / San Sebastian

  • Institut Català d' Oncologia L'Hospitalet (ICO)

    L'Hospitalet de Llobregat

  • Hospital Ramón y Cajal

    Madrid

  • Hospital Arnau de Vilanova de Valencia

    Valencia

Other trials in Spain

About this study

Official title: A Two-stage Simon Design Phase II Study for NOn-BRCA Metastatic BReast Cancer (MBC) Patients With Homologous Recombination Deficiency Treated With OLAparib Single Agent

This is an international, multi-centre, non-controlled, open-label, single arm, two-stage Simon Design phase II study for non-BRCA metastatic breast cancer (MBC) patients with homologous recombination deficiency treated with Olaparib single agent.

The main objective is to assess the efficacy of olaparib single agent as determined by Clinical Benefit Rate (CBR) using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Read more

In the first stage Triple negative (TN) non-BRCA, metastatic breast cancer (MBC) patients whose tumours exhibited any characteristic related to homologous recombination deficiency (HRD). In the second stage, luminal patients (RH positive HER2 negative) will be allowed in the same conditions that TN.

Patients whose tumours are identified as Homologous Recombination Deficient by deleterious HRR gene mutations (according to Foundation Medicine's Foundation One assay) will receive olaparib 300 mg (two tablets of 150mg) orally twice daily (bid) on days 1-28 each 28 days.

Study commitment is 39 patients: 17 patients will be enrolled at first stage and 22 at the second stage.

The total duration of the study period is 34 months.

Read the detailed description

This is an international, multi-centre, non-controlled, open-label, single arm, two-stage Simon Design phase II study for non-BRCA metastatic breast cancer (MBC) patients with homologous recombination deficiency treated with Olaparib single agent.

The main objective is to assess the efficacy of olaparib single agent as determined by Clinical Benefit Rate (CBR) using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Triple negative non-BRCA metastatic breast cancer women (for the first stage) age ≥ 18 years that had previously received at least one (and no more than three) line for their metastatic disease. Patients must have previously received taxanes either in the early or in the metastatic scenario. To be included in the trial, tumours must be considered homologous recombination deficient (HRD) according to Foundation Medicine's Foundation One assay. Evidence of measurable metastatic disease is required.

In the second stage, luminal patients (RH positive HER2 negative) will be allowed to participate in the same conditions that TN patients.

Patients whose tumours are identified as Homologous Recombination Deficient by deleterious HRR gene mutations (according to Foundation Medicine's Foundation One assay) will receive olaparib 300 mg (two tablets of 150mg) orally twice daily (bid) on days 1-28 each 28 days.

Study commitment is 39 patients: 17 patients will be enrolled at first stage and 22 at the second stage.

During the period between the end of the first stage and the beginning of the second, an interim analysis will be conducted to assess the viability of the second part of the trial.

The total duration of the study period is 34 months.

Stage I:

  • Recruitment period: 10 months
  • Follow-up period: Up to 6 months after last patient included in the study

Stage II:

  • Recruitment period: 12 months
  • Follow-up period: up to 6 months after last patient included in the study
Conditions
Breast Cancer
Being tested
Olaparib
Medical subject headings
Breast Neoplasms

What participants receive

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

  • OlaparibDrug

    Also called Lynparza, AZD2281

    Olaparib 300 mg twice a day (orally) beginning on Day 1 and continuing through Day 28 of every 28-day cycle.

Study groups in NCT03367689
Study groupRoleWhat they receive
Olaparib 300 mgExperimentalPatients whose tumours are identified as Homologous Recombination Deficient, will receive olaparib 300 mg (two tablets of 150mg) orally twice daily (bid) on days 1-28 each 28 days.
Receives: Drug: Olaparib

What is being measured

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

  1. To assess the efficacy of olaparib single agent in non-BRCA MBC patients whose tumours exhibit an homologous recombination deficiency (HRD) signature, as determined by Clinical Benefit Rate (CBR) using RECIST 1.1 criteria

    The CBR as best response, defined as the percentage of patients who experience a complete response, partial response or stable disease for at least 24 weeks and assessed by modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria

    Measured: Baseline up to 24 weeks

Secondary outcomes (6)

  1. To assess the accuracy of Foundation One's HRR assay in predicting the proportion of patients with response to olaparib.

    The positive predictive value (PPV) of the signature to predict patients that achieved objective response and clinical benefit.

    Measured: Baseline up to 34 months

  2. To assess incidence of Treatment-Emergent Adverse Events (Safety profile) of olaparib in this population

    This study will consider the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v4.03 criteria) grade 3 and 4 events (AEs) and serious AEs (SAEs) in order to assess the safety and tolerability objectives.

    Measured: Baseline up to 34 months

  3. To investigate the prevalence of HRD signature within triple negative and luminal non-BRCA patients' cohorts

    The percentage of patients with HRD according to the Foundation Medicine's Foundation One assay within triple negative and luminal (in the second stage) non-BRCA patients' cohorts

    Measured: Baseline up to 34 months

  4. To explore the efficacy of olaparib in terms of Progression-free survival (PFS)

    The PFS defined as the time from the first dose of study drugs until objective tumour progression or death, as assessed by the investigator per RECIST v1.1.

    Measured: Baseline up to 34 months

  5. To explore the efficacy of olaparib in terms of objective response rate (ORR)

    The ORR defined as the proportion of patients with best objective response of confirmed complete response (CR) or partial response (PR) according to RECIST criteria guidelines (version 1.1).

    Measured: Baseline up to 34 months

  6. To explore the efficacy of olaparib in terms of overall survival (OS)

    The OS defined as the time from the first dose of study drugs until death from any cause or the last date the patient was known to be alive.

    Measured: Baseline up to 34 months

Timeline

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

  1. First posted11 Dec 2017
  2. Study start17 Apr 2018
  3. Primary completion31 Jul 2021
  4. Study completion31 Dec 2021

Why it stopped: Very slow recruitment due to subject profile

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
Not applicable
Intervention model
Single group
Model description
This is an international, multi-centre, non-controlled, open-label, single arm, two-stage Simon Design phase II study.
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03367689
Sponsor's protocol ID
MedOPP100
Other IDs
2016-002892-80, 2016
Acronym
NOBROLA
Status last verified
Jun 2022
First submitted
24 Nov 2017
Last updated
22 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Cortes A, Lopez-Miranda E, Fernandez-Ortega A, Caranana V, Servitja S, Urruticoechea A, Lema-Roso L, Marquez A, Lazaris A, Alcala-Lopez D, Mina L, Gener P, Rodriguez-Morato J, Antonarelli G, Llombart-Cussac A, Perez-Garcia J, Cortes J. Olaparib monotherapy in advanced triple-negative breast cancer patients with homologous recombination deficiency and without germline mutations in BRCA1/2: The NOBROLA phase 2 study. Breast. 2024 Dec;78:103834. doi: 10.1016/j.breast.2024.103834. Epub 2024 Nov 3.

    PubMed 39520738

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaparib in people with Breast Cancer, run by MedSIR at 5 sites in Spain.

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 18 inclusion and 29 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: stopped early, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Spain. 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?

The study was stopped early (reason given: Very slow recruitment due to subject profile). Results are not available in the source record.

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?

To assess the efficacy of olaparib single agent in non-BRCA MBC patients whose tumours exhibit an homologous recombination deficiency (HRD) signature, as determined by Clinical Benefit Rate (CBR) using RECIST 1.1 criteria (time frame: Baseline up to 24 weeks). 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 NCT03367689, 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 22 Feb 2023.

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NOBROLA Clinical Trial NCT03367689 | AzTrials