Olaparib and Radiotherapy in Inoperable Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02227082
Recruitment Status : Recruiting
First Posted : August 27, 2014
Last Update Posted : March 13, 2018
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief 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 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.

Condition or disease Intervention/treatment Phase
Locally Advanced Malignant Neoplasm Inflammatory Breast Carcinoma Triple-Negative Invasive Breast Carcinoma Radiation: radiotherapy Drug: olaparib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Olaparib Dose Escalation in Combination With High Dose Radiotherapy to the Breast Andregional Lymph Nodes in Patients With Breast Cancer
Actual Study Start Date : October 21, 2013
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Olaparib

Arm Intervention/treatment
Experimental: radiotherapy and olaparib
radiotherapy: 61.18 Gy olaparib: dose escalating
Radiation: radiotherapy
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

Drug: olaparib
The pre-defined dose levels of olaparib are 25mg QD, 25, 50, 100, 200, 300 and 400 mg BID
Other Names:
  • AZD2281
  • KU-0059436

Primary Outcome Measures :
  1. The incidence of dose limiting toxicities. [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Acute toxicity [ Time Frame: 3 months after treatment ]
    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

  2. Late toxicity [ Time Frame: 3 months until 2 years after end of treatment ]
    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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • ≥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
  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02227082

Contact: Gabe Sonke, MD, PhD + 31 20 512 2951
Contact: Rosemarie de Haan, MD + 31 20 512 9085

The Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Gabe Sonke, MD, PhD    + 31 20 512 29251   
Contact: Rosemarie de Haan, MD    + 31 20 512 9085   
Principal Investigator: Gabe Sonke, MD, PhD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Principal Investigator: Gabe Sonke, MD, PhD The Netherlands Cancer Institute
Principal Investigator: Marcel verheij, MD, PhD The Netherlands Cancer Institute

Responsible Party: The Netherlands Cancer Institute Identifier: NCT02227082     History of Changes
Other Study ID Numbers: N13ORB
2011-001586-40 ( EudraCT Number )
First Posted: August 27, 2014    Key Record Dates
Last Update Posted: March 13, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The Netherlands Cancer Institute:
breast cancer
locally advanced breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Breast Diseases
Skin Diseases
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents