A Study of Olaparib With Concomitant Radiotherapy in Locally Advanced/Unresectable Soft-tissue Sarcoma

NCT02787642 | Completed Phase 1 Results DMC

• 2 other identifiers: IB 2015-052015-003722-13
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

Brief Summary

A phase Ib study of Olaparib with concomitant radiotherapy in locally advanced/unresectable soft-tissue sarcoma.

Conditions

Soft-tissue Sarcoma

Keywords

Advanced soft-tissue sarcoma; Unresectable Soft-tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  We reported in the following the number of Participants who experienced DLT. A DLT is defined as an adverse event (AE) or laboratory abnormality that fulfills all the criteria below: 1/ Occurs during the period of observation of DLTs defined as the period between the first day of treatment administration and up to 6 weeks after the end of radiotherapy. 2/ Is considered to be at least possibly related to the treatment strategy (radiotherapy or Olaparib).3/ Is unrelated to disease, disease progression, inter-current illness, or concomitant medications. 4/ Meets some criteria (see protocole), graded according to NCI CTCAEv4.0

  Until to six weeks after end of radiotherapy

• Maximum Tolerated Dose (MTD) of Olaparib in Association With Radiotherapy

  MTD was determined by testing increasing doses up 150mg twice a day on dose escalation cohorts 1 to 4 with 3 to 11 participants each. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined as any grade 3 or 4 adverse event according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0) that could be related to treatment (reported in the following primary outcome measure).

  Up to 6 weeks after end of radiotherapy for each dosing cohort

Secondary Outcomes (6)

• Percentage of Participants With Non-progression at 6 Months as Per RECIST 1.1

  up to 6-month after treatment onset

• Percentage of Participants With Objective Responses at 6 Months as Per RECIST 1.1

  up to 6-month after treatment onset

• Best Response Under Treatment as Per RECIST 1.1

  End of treatment, approximately 13.5 weeks atfer treatment onset

• Progression-free Survival (PFS) as Per RECIST 1.1

  1 year after treatment onset

• Overall Survival (OS)

  1 year after treatment onset

Study Arms (1)

Olaparib in association with concomitant radiotherapy

EXPERIMENTAL

Olaparib will be administered per os bi-daily, as appropriate assigned dose level, during 7.5 weeks (D1 to D52). Olaparib should be started one week before the start of radiotherapy and will be continued until the last day of radiotherapy. Beyond this period, Olaparib could be continued at the investigator's discretion and after sponsor authorization, until progression. Radiotherapy consists of fractionated focal irradiation at a dose of 1.8 Grays (Gy) per fraction given once daily five days per week (Monday through Friday) over a period of 6.5 weeks, for a total dose of 59.4 Gy. Radiotherapy starts at D8.

Drug: Olaparib; Radiation: Concomitant Radiotherapy

Interventions

Olaparib DRUG

Olaparib will be administered per os bidaily, as appropriate assigned dose level, during 7.5 weeks (D1 to D52). Olaparib should be started one week before the start of radiotherapy and will be continued until the last day of radiotherapy. Beyond this period, Olaparib could be continued at the investigator's discretion and after sponsor authorization, until progression.

Olaparib in association with concomitant radiotherapy

Concomitant Radiotherapy RADIATION

Radiotherapy consists of fractionated focal irradiation at a dose of 1.8 Grays (Gy) per fraction given once daily five days per week (Monday through Friday) over a period of 6.5 weeks, for a total dose of 59.4 Gy. Radiotherapy starts at D8.

Olaparib in association with concomitant radiotherapy

Eligibility Criteria

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

You may qualify if:

• Histology: patients with soft-tissue sarcoma histologically confirmed by central review (Pr Coindre team), except if the diagnosis was already confirmed by the RRePS Network,
• Upper/Lower limb or trunk wall soft-tissue sarcoma,
• Age ≥ 18 years,
• Locally advanced or locally recurrent primitive tumor, outside any previously irradiated field. Patients presenting operable locally Advanced or lacally recurrent tumor can be included. Patients with metastases can be included.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2,
• Life expectancy ≥ 6 months,
• At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements,
• Adequate hematological, renal, metabolic and hepatic function:
• Haemoglobin ≥ 9 g/dL and no blood transfusions in the 14 days prior to study entry
• Absolute neutrophil count (ANc) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x upper limit of normality (ULN),
• Alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) ≤ 2.5 x ULN,
• Serum creatinine ≤ 150 μmol/L or creatinine clearance ≥ 50 mL/min (according to local institution) in case of serum creatinine \> 150 μmol/L,
• TP, INR ≤ 1.5 x ULN

You may not qualify if:

• Any previous treatment with a PARP inhibitor, including Olaparib,
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication,
• Immunocompromised patients, e.g., 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) due to risk of transmitting the infection through blood or other body fluids,
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan or any psychiatric disorder that prohibits obtaining informed consent,
• Patients with uncontrolled seizures,
• Men or women of childbearing potential who are not using an effective method of contraception as previously describes; women who are pregnant or breast feeding,
• No prior or concurrent malignant disease diagnosed or treated in the last 2 years, except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
• Patients receiving any systemic chemotherapy within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used),
• Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir,
• Resting ECG with QTc \> 470msec 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 study start,
• Patients with myelodysplastic syndrome/acute myeloid leukaemia,
• Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery,
• Participation to a study involving a medical or therapeutic intervention in the last 30 days,

Sponsors & Collaborators

• Institut Bergonié: lead
• National Cancer Institute, France: collaborator

Study Sites (4)

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut du Cancer de Montpellier

Montpellier, 34298, France

Location

Institut Claudius Regaud - IUCT

Toulouse, 31052, France

Location

Related Publications (2)

• Sargos P, Sunyach MP, Ducassou A, Llacer C, Dinart D, Michot A, Valentin T, Firmin N, Blay JY, Gillon P, Bellera C, Italiano A. Results of a phase Ib study of olaparib with concomitant radiotherapy in soft-tissue sarcoma: a French sarcoma group study. Ann Oncol. 2025 May;36(5):592-600. doi: 10.1016/j.annonc.2025.01.016. Epub 2025 Jan 31.

  PMID: 39894354 RESULT

• Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

  PMID: 32827353 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Coordinating Investigator
• Organization: Institut Bergonie

p.sargos@bordeaux.unicancer.fr

05.56.33.33.33

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: May 2, 2016
• First Posted: June 1, 2016
• Study Start: January 1, 2016
• Primary Completion: October 1, 2021
• Study Completion: May 1, 2022
• Last Updated: February 25, 2026
• Results First Posted: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)