Olaparib and Radiotherapy in Inoperable Breast Cancer

NCT02227082 | Completed Phase 1

• 2 other identifiers: N13ORB2011-001586-40
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Locally Advanced Malignant Neoplasm; Inflammatory Breast Carcinoma; Triple-Negative Invasive Breast Carcinoma

Keywords

radiotherapy; olaparib; breast cancer; locally advanced breast cancer

Outcome Measures

Primary Outcomes (1)

• The incidence of dose limiting toxicities.

  1 year

Secondary Outcomes (2)

• Acute toxicity

  3 months after treatment

• Late toxicity

  3 months until 2 years after end of treatment

Study Arms (1)

radiotherapy and olaparib

EXPERIMENTAL

radiotherapy: 61.18 Gy olaparib: dose escalating

Radiation: radiotherapy; Drug: olaparib

Interventions

radiotherapy RADIATION

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

radiotherapy and olaparib

olaparib DRUG

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

Also known as: AZD2281, KU-0059436

radiotherapy and olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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:

You may not qualify if:

• 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:

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

The Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 31500595 DERIVED

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Breast Neoplasms

Interventions

Radiotherapy; olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Gabe Sonke, MD, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

• Marcel verheij, MD, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 27, 2014
• Study Start: October 21, 2013
• Primary Completion: September 1, 2019
• Study Completion: August 1, 2020
• Last Updated: August 4, 2021

Record last verified: 2021-08

Locations

NL (1)