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Locally Advanced Malignant NeoplasmPhase 1NCT02227082

Olaparib and Radiotherapy in Inoperable Breast Cancer

A Phase 1 study testing radiotherapy and olaparib in people with Locally Advanced Malignant Neoplasm and Inflammatory Breast Carcinoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Completed

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

Official record
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Trial summary

The majority of breast cancer patients receive radiotherapy as part of their treatment. Radiotherapy improves both locoregional control and overall survival. In most patients with breast cancer the locoregional recurrence rate (LRR) is low, however still high LRRs are found in certain patient groups, especially in… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
radiotherapy and olaparib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteNetherlands
Study dates
21 Oct 2013to Aug 2020
Phase
Phase 1
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

  • ≥18 years of age
  • Histological proven breast cancer or local recurrence of breast cancer which is inoperable or/and metastatic, including inflammatory breast cancer
  • No participation in trial with neoadjuvant systemic treatment, except for previous contralateral breast cancer
  • Tumor in breast accessible for biopsy
  • WHO performance 0-2
  • Life expectancy of at least 6 months
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  • Adequate hematological, renal and hepatic functions
  • Hemoglobin 6.2 mmol/l
  • Leucocytes 3.0 x 10E9/l
  • Absolute neutrophil count 1.5x10E9/l
  • Platelet count 100 x 10E9/l
  • Total bilirubin ≤ 1.5 x ULN
  • ASAT/ALAT ≤ 2.5 x ULN; or in the presence of liver metastases ≤ 5 x ULN
  • Creatinine clearance 50 ml/min; measured or calculated
  • Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 21 days of study treatment. Non-childbearing potential or postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • LH and FSH levels in post menopausal range for women under 50 years of age
  • Radiation-induced oophorectomy with last menses > 1 year ago
  • Chemotherapy-induced menopause with > 1 year interval since last menses
  • Surgical sterilisation (bilateral oophorectomy or hysterectomy)
  • Patients of reproductive potential must agree to practice two effective medically approved contraceptive method during the trial and 3 months afterwards
  • Signed written informed consent

Who cannot join

  • Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within 3 weeks prior to start of therapy (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin ornitrosourea). Patient may continue the use of tamoxifen, aromatase inhibitor and LHRH agonists for cancer; bisphosphonates for bone disease and corticosteroids. The use of denosumab for bone disease is not allowed.
  • Major surgery within two weeks of starting study treatment.
  • Participation in other trial with investigational drug or treatment modality
  • Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required.
  • Prior ipsilateral radiotherapy to the chest or breast.
  • Blood transfusion in the four weeks prior to study entry
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  • Persistent toxicities (CTC ≥ grade 2) with the exception of alopecia, caused by previous cancer therapy
  • QT-interval > 470 msec
  • Significant cardiovascular disease as defined by
  • History of congestive heart failure defined as NYHA class III
  • History of unstable angina pectoris or myocardial infarction up to 3 months prior to trial entry;
  • Presence of severe valvular heart disease
  • Presence of a ventricular arrhythmia requiring treatment;
  • Uncontrolled hypertension
  • Patients considered a poor medical risk due to:
  • non-malignant systemic disease
  • active, uncontrolled infection requiring parenteral antibiotics
  • a serious, uncontrolled medical disorder; examples include, but are not limited to:
  • uncontrolled major seizure disorder
  • unstable spinal cord compression
  • superior vena cava syndrome
  • extensive bilateral lung disease on HRCT scan
  • any psychiatric disorder that prohibits obtaining informed consent.
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  • Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
  • Patients with known active hepatic disease (i.e. Hepatitis B or C)
  • Patients with myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of MDS/AML on peripheral blood smear.
  • Gastrointestinal disorders that may interfere with absorption of the study drug or patients who are not able to take oral medication
  • Concomitant medications:
  • Any previous treatment with a PARP inhibitor, including Olaparib
  • Patients receiving the following classes of inhibitors of CYP3A4 (see Section 6.4.2 for guidelines and wash out periods)
  • Azole antifungals
  • Macrolide antibiotics
  • Protease inhibitors
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product
  • Breast-feeding women

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • The Netherlands Cancer Institute

    Amsterdam, 1066 CX

Other trials in Netherlands

About this study

Official title: Olaparib Dose Escalation in Combination With High Dose Radiotherapy to the Breast Andregional Lymph Nodes in Patients With Breast Cancer

The majority of breast cancer patients receive radiotherapy as part of their treatment. Radiotherapy improves both locoregional control and overall survival. In most patients with breast cancer the locoregional recurrence rate (LRR) is low, however still high LRRs are found in certain patient groups, especially in locally advanced, inflammatory and triple negative breast cancer. Olaparib is a potent PARP inhibitor developed as an anti-cancer drug for homologous recombination (HR) defected tumors and as a dose intensifier for chemo- and radiotherapy. The combination of olaparib and radiotherapy is expected to improve locoregional control and thereby overall survival in both breast cancer patients with a high probability of locoregional recurrence and patients with HR deficient tumors. However, this combination treatment has never been tested in humans before. The purpose of this study is to determine the safety and tolerability of radiotherapy to the breast and regional lymph nodes with concurrent olaparib.

Being tested
radiotherapy, olaparib
Keywords
radiotherapy, olaparib, breast cancer, locally advanced breast cancer
Medical subject headings
Inflammatory Breast Neoplasms, Breast Neoplasms

What participants receive

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

  • radiotherapyRadiation

    The whole breast and regional lymph nodes will receive 23 x 2.03 Gy per fraction (total 46.69 Gy) At the macroscopic tumor a added SIB will be given of 23 x 0.63Gy . Total dose: 61.18 Gy

  • olaparibDrug

    Also called AZD2281, KU-0059436

    The pre-defined dose levels of olaparib are 25mg QD, 25, 50, 100, 200, 300 and 400 mg BID

Study groups in NCT02227082
Study groupRoleWhat they receive
radiotherapy and olaparibExperimentalradiotherapy: 61.18 Gy olaparib: dose escalating
Receives: Radiation: radiotherapy; Drug: olaparib

What is being measured

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

  1. The incidence of dose limiting toxicities.

    Measured: 1 year

Secondary outcomes (2)

  1. Acute toxicity

    severity, duration and relation with treatment of all adverse events according to CTCAE version 4.03 occurring from start of treatment until 3 months after end of treatment

    Measured: 3 months after treatment

  2. Late toxicity

    severity, duration and relation with treatment of all adverse events that are possibly, probably or definitely related to the combination treatment according to CTCAE version 4.03

    Measured: 3 months until 2 years after end of treatment

Timeline

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

  1. First posted27 Aug 2014 (estimated)
  2. Study start21 Oct 2013
  3. Primary completionSep 2019
  4. Study completionAug 2020

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02227082
Sponsor's protocol ID
N13ORB
Other IDs
2011-001586-40
Status last verified
Aug 2021
First submitted
26 Aug 2014
Last updated
4 Aug 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • de Haan R, van Werkhoven E, van den Heuvel MM, Peulen HMU, Sonke GS, Elkhuizen P, van den Brekel MWM, Tesselaar MET, Vens C, Schellens JHM, van Triest B, Verheij M. Study protocols of three parallel phase 1 trials combining radical radiotherapy with the PARP inhibitor olaparib. BMC Cancer. 2019 Sep 10;19(1):901. doi: 10.1186/s12885-019-6121-3.

    PubMed 31500595

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing radiotherapy and olaparib in people with Locally Advanced Malignant Neoplasm and Inflammatory Breast Carcinoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

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 22 inclusion and 36 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 4 Aug 2021. 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 Netherlands. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The incidence of dose limiting toxicities. (time frame: 1 year). 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 NCT02227082, 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 4 Aug 2021.

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