Olaparib & Radiation Therapy for Patients Triple Negative Breast Cancer (TNBC)

NCT03109080 | Completed Phase 1 DMC

• 2 other identifiers: IC 2016-01 RadioPARP2016-001837-28
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I of Olaparib with Radiation Therapy in Patients With Inflammatory, Loco-regionally Advanced or Metastatic TNBC (triple negative breast cancer) or Patient With Operated TNBC with Residual Disease.

Conditions

Breast Neoplasms, Triple-Negative; Breast Neoplasm Malignant Female; Radiotherapy Side Effect

Outcome Measures

Primary Outcomes (1)

• Determination of the Maximal Tolerated Dose of Olaparib administered with concurrent loco regional radiotherapy

  Incidence of early Dose Limited Toxicity (DLTs: early adverse effects related to Olaparib administered with concurrent radiotherapy) to determinate the Maximal Tolerated Dose (MTD) of Olaparib administered with concurrent loco regional radiotherapy in patients who have triple negative inflammatory, loco-regional advanced or metastatic breast cancer either inoperable after neoadjuvant chemotherapy or operated patient with residual disease (after neoadjuvant chemotherapy).

  2 years

Secondary Outcomes (15)

• Incidence of Serious Adverse Events (SAEs), graded according to NCI-CTCAE version 4.03 criteria to assess the safety profile of Olaparib administered with concurrent loco-regional radiotherapy.

  2 years

• Incidence and severity of Adverse Events (AEs), graded according to NCI-CTCAE version 4.03 criteria to assess the safety profile of Olaparib administered with concurrent loco-regional radiotherapy.

  2 years

• Incidence and severity of laboratory abnormalities, graded according to NCI-CTCAE version 4.03 criteria to assess the safety profile of Olaparib administered with concurrent loco-regional radiotherapy.

  2 years

• Incidence of acute toxicity 2 weeks and 6 weeks after the end of radiotherapy to assess the safety profile of Olaparib administered with concurrent loco-regional radiotherapy.

  2 years

• Incidence of late toxicity at 1 year and at 2 years as of initiation of radiation therapy to assess the safety profile of Olaparib administered with concurrent loco-regional radiotherapy.

  2 years

Study Arms (1)

Olaparib + radiation therapy

EXPERIMENTAL

One week of Olaparib alone followed by 5 weeks of Olaparib and concurrent loco-regional radiotherapy. Five levels of dose of Olaparib are expected.

Drug: Olaparib; Radiation: Radiation therapy

Interventions

Olaparib DRUG

five levels of dose, per os administration, twice daily each day

Also known as: PARP (Poly (Adenosine diphosphate [ADP]-Ribose) Polymerase) inhibitor, Lynparza, AZD-2281

Olaparib + radiation therapy

Radiation therapy RADIATION

3D conformal radiotherapy or intensity-modulated radiotherapy (IMRT), Simultaneous Integrated Boost (SIB), postoperative radiotherapy

Also known as: Radiotherapy

Olaparib + radiation therapy

Eligibility Criteria

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

You may qualify if:

• Woman aged \>18 years.
• Histologically confirmed triple negative breast cancer with loco-regional radiotherapy indication :
• Non-operated with either:
• Inflammatory breast cancer in progression during neoadjuvant chemotherapy or inoperable after neoadjuvant chemotherapy.
• Loco-regional advanced breast cancer in progression during neoadjuvant chemotherapy or inoperable after neoadjuvant chemotherapy (T ≥ 3 and/or N ≥ 1; with evaluable disease according to RECIST 1.1 criteria).
• Non operable metastatic breast cancer (all T, all N, M1; with evaluable disease according to RECIST 1.1 criteria) needing local and regional treatment in case of good metastatic control after chemotherapy.
• Or patient operated after neoadjuvant treatment and surgery with residual disease (non-pCR and/or pN+ disease).
• Neoadjuvant chemotherapy (containing anthracyclines or taxanes or the combination of both or containing platinum-based chemotherapy) willingness to discontinue any cytotoxic chemotherapeutic agents, immunotherapy, and targeted therapies at least two weeks prior to start of Olaparib.
• ECOG performance status \< 2.
• Life expectancy greater than 6 months.
• Adequate hematologic, renal and hepatic function (assessed within the two weeks prior to registration and within the month prior to the commencement of protocol treatment). For patients who have stopped chemotherapy two weeks prior to protocol treatment, hematologic function must be re-assessment 1 or 2 days before the first Olaparib intake:
• Haemoglobin ≥ 10.0 g/dL.
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.
• White Blood Cells (WBC) \> 3 x 109/L.
• Platelet count ≥ 100 x 109/L.

You may not qualify if:

• Radiation therapy: prior history of radiation therapy to the ipsilateral breast and/or regional nodes (except prior radiation therapy to other sites).
• Patient with unresolved or unstable, NCI-CTCAE v4.03 (National Cancer Institute Common Toxicity Criteria for Adverse Events) Grade 3 or greater toxicity from prior administration of prior anti-cancer treatment.
• Patient with clinically and uncontrolled significant comorbidity: major cardiac, respiratory, renal, hepatic, gastrointestinal, hematologic or neurological/psychiatric disease or disorder, including but not limited to: active uncontrolled infection; symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia; any other illness condition(s) that could exacerbate potential toxicities, require excluded therapy for management, or limit compliance with study requirements.
• Patient with second primary cancer, except : adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years.
• Concomitant anti-cancer treatment during protocol treatment and/or not completed at least 2 weeks prior to Olaparib initiation, except bisphosphonates and RANK inhibitors without restriction even during protocol treatment as long as these where started at least 4 weeks prior to study treatment initiation.
• Any previous treatment with a PARP (Poly (Adenosine diphosphate \[ADP\]-Ribose) Polymerase) inhibitor, including Olaparib.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Olaparib.
• Patient being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itraconazole, Voriconazole, Ritonavir, Telithromycin) within the last 7 days before first Olaparib intake.
• Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• Blood transfusions within 14 days prior to treatment start.
• Patient with myelodysplastic syndrome / acute myeloid leukaemia.
• Pregnant or breastfeeding woman.
• Patient already included in another clinical trial with an investigational drug.
• Patient individually deprived of liberty or placed under the authority of a tutor.
• Patient with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Sponsors & Collaborators

• Institut Curie: lead
• AstraZeneca: collaborator

Study Sites (1)

Institut Curie

Paris, 75005, France

Location

Related Publications (2)

• Loap P, Loirat D, Berger F, Ricci F, Vincent-Salomon A, Ezzili C, Mosseri V, Fourquet A, Ezzalfani M, Kirova Y. Combination of Olaparib and Radiation Therapy for Triple Negative Breast Cancer: Preliminary Results of the RADIOPARP Phase 1 Trial. Int J Radiat Oncol Biol Phys. 2021 Feb 1;109(2):436-440. doi: 10.1016/j.ijrobp.2020.09.032. Epub 2020 Sep 21.

  PMID: 32971187 RESULT

• Loap P, Loirat D, Berger F, Rodrigues M, Bazire L, Pierga JY, Vincent-Salomon A, Laki F, Boudali L, Raizonville L, Mosseri V, Jochem A, Eeckhoutte A, Diallo M, Stern MH, Fourquet A, Kirova Y. Concurrent Olaparib and Radiotherapy in Patients With Triple-Negative Breast Cancer: The Phase 1 Olaparib and Radiation Therapy for Triple-Negative Breast Cancer Trial. JAMA Oncol. 2022 Dec 1;8(12):1802-1808. doi: 10.1001/jamaoncol.2022.5074.

  PMID: 36301572 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Radiation Injuries

Interventions

olaparib; Poly A; Adenosine Diphosphate; Adenosine Diphosphate Ribose; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Polyribonucleotides; Polynucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ribonucleotides; Adenosine Diphosphate Sugars; Nucleoside Diphosphate Sugars; Glycosides; Carbohydrates; Therapeutics

Study Officials

• Youlia KIROVA, MD

  Institut Curie

  STUDY DIRECTOR

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: March 2, 2017
• First Posted: April 12, 2017
• Study Start: July 24, 2017
• Primary Completion: February 17, 2020
• Study Completion: November 29, 2021
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (1)