Olaparib Dose Escalation in Combination With High Dose Radiotherapy to the Breast Andregional Lymph Nodes in Patients With Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- radiotherapy
- Conditions
- Locally Advanced Malignant Neoplasm
- Sponsor
- The Netherlands Cancer Institute
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- The incidence of dose limiting toxicities.
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility 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
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
Arms & Interventions
radiotherapy and olaparib
radiotherapy: 61.18 Gy olaparib: dose escalating
Intervention: radiotherapy
radiotherapy and olaparib
radiotherapy: 61.18 Gy olaparib: dose escalating
Intervention: olaparib
Outcomes
Primary Outcomes
The incidence of dose limiting toxicities.
Time Frame: 1 year
Secondary Outcomes
- Acute toxicity(3 months after treatment)
- Late toxicity(3 months until 2 years after end of treatment)