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Olaparib and Radiotherapy in Inoperable Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by The Netherlands Cancer Institute
Sponsor:
Information provided by (Responsible Party):
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT02227082
First received: August 26, 2014
Last updated: NA
Last verified: July 2013
History: No changes posted
  Purpose

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 Intervention Phase
Locally Advanced Malignant Neoplasm
Inflammatory Breast Carcinoma
Triple-Negative Invasive Breast Carcinoma
Radiation: radiotherapy
Drug: olaparib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Olaparib Dose Escalation in Combination With High Dose Radiotherapy to the Breast and Regional Lymph Nodes in Patients With Inoperable, Metastatic or Inflammatory Breast Cancer

Resource links provided by NLM:


Further study details as provided by The Netherlands Cancer Institute:

Primary Outcome Measures:
  • The incidence of dose limiting toxicities. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Acute toxicity [ Time Frame: 3 months after treatment ] [ Designated as safety issue: Yes ]
    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

  • Late toxicity [ Time Frame: 3 months until 2 years after end of treatment ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 36
Study Start Date: October 2013
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 LHRH agonists for cancer; biphosphonates for bone disease and corticosteroids.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02227082

Contacts
Contact: Gabe Sonke, MD, PhD + 31 20 512 2951 g.sonke@nki.nl
Contact: Rosemarie de Haan, MD + 31 20 512 9085 r.d.haan@nki.nl

Locations
Netherlands
The Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Gabe Sonke, MD, PhD    + 31 20 512 29251    g.sonke@nki.nl   
Contact: Rosemarie de Haan, MD    + 31 20 512 9085    r.d.haan@nki.nl   
Principal Investigator: Gabe Sonke, MD, PhD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Investigators
Principal Investigator: Gabe Sonke, MD, PhD The Netherlands Cancer Institute
  More Information

No publications provided

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02227082     History of Changes
Other Study ID Numbers: N13ORB, 2011-001586-40
Study First Received: August 26, 2014
Last Updated: August 26, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

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

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Inflammatory Breast Neoplasms
Neoplasms
Breast Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Skin Diseases

ClinicalTrials.gov processed this record on November 25, 2014