Study Evaluating the Efficacy of a Double Immunotherapy Combined With Olaparib in Patients With Solid Cancers and Carriers of Homologous Recombination Repair Genes After Olaparib Treatment

NCT04169841 | Active Not Recruiting Phase 2

• 1 other identifier: GUIDE2REPAIR
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 8

Brief Summary

The study propose to generate a clinical trial based on precision medicine to evaluate the use of immunotherapy in patients with altered homologous recombination repair genes and without progression after prior targeted therapy.

Conditions

Immunotherapy

Keywords

immunotherapy; olaparib; durvalumab; tremelimumab; genes mutation

Outcome Measures

Primary Outcomes (1)

• Safety Assessments: progression free survival

  progression free survival

  6 months after the initiation of immunotherapy for all cohorts excepted for ovarian cohort where PFS will be evaluated at 12 months.

Study Arms (1)

GUIDE2REPAIR patients

EXPERIMENTAL

olaparib + immunotherapy (durvalumab + tremelimumab) during 4 months followed by durvalumab alone as maintenance in patients with solid cancer and in response or stable after prior molecular target therapy by olaparib based on molecular sequencing.

Drug: olaparib, durvalumab, tremelimumab

Interventions

olaparib, durvalumab, tremelimumab DRUG

STEP 1: Olaparib 300 mg BID during 8 weeks. Olaparib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets can be taken with or without food STEP 2: Olaparib 300 mg during 4 months as per same requirement as below. Durvalumab 1500 mg plus tremelimumab 75 mg via IV infusion Q4W, starting on Week 0, for up to a maximum of 4 doses followed by durvalumab monotherapy 1500 mg via IV infusion Q4W, starting 4 weeks after the last infusion of the combination and in response or stable after prior molecular target therapy by olaparib based on molecular sequencing.

GUIDE2REPAIR patients

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent
• Exome sequencing of tumor and constitutive DNA should have been already performed
• Metastatic breast cancer:
• In second line
• third line and after
• Metastatic lung cancer:
• Non-small cell lung cancer
• Must have progressed after at least a first line with platinum based therapy
• Metastatic head and Neck cancer
• Must have progressed after at least a first line with platinum based therapy
• Metastatic endometrial cancer • Progression after 1 prior systemic, platinum-based chemotherapy regimen for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting. There is no restriction regarding prior hormonal therapy
• Metastatic clear cell renal cancer
• Must have progressed after at least a line with anti-angiogenic agent. Metastatic pancreatic cancer
• Must have progressed after at least a line with FOLFIRINOX regimen and/or Gemcitabin based chemotherapy
• Locally advanced or metastatic ovarian cancer

You may not qualify if:

• Involvement in the planning and/or conduct of the study
• Patient with mBRCA1 / 2 that are eligible for current marketing authorization for olaparib (ovarian cancer),and patient eligible for AstraZeneca registration clinical trials, particularly for the prostate cohort
• Metastatic breast cancer:
• Only for patient second line : patient with mBRCA1 / 2 that are eligible for current marketing authorization for Olaparib (ovarian cancer) and patient eligible for AstraZeneca registration clinical trials).
• Metastatic lung cancer
• Small cell cancer
• oncogenic addiction : EGFR mutation or BRAF mutation or ALK rearrangement or ROS1 mutation Locally advanced or metastatic ovarian cancer
• Patient with mBRCA1 / 2 that are eligible for current marketing authorization for Olaparib (ovarian cancer) and patient eligible for AstraZeneca registration clinical trials.
• Metastatic prostate cancer
• Untreated or first line patients
• Metastatic head and Neck cancer, Metastatic endometrial cancer, Metastatic clear cell renal cancer, Metastatic pancreatic cancer \& Metastatic urothelial cancer:
• None
• Participation in another clinical study with an investigational product during within 2 months of first administration of Olaparib.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Receipt of the last dose of anticancer therapy ≤21 days prior to the first dose of olaparib or 5 times its half-life, whichever is less.

Sponsors & Collaborators

• Centre Georges Francois Leclerc: lead
• AstraZeneca: collaborator

Study Sites (8)

CHU Amiens

Amiens, France

Location

CHRU Jean Minjoz

Besançon, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre Georges François Leclerc

Dijon, 21000, France

Location

CHU François Mitterrand

Dijon, France

Location

Institut Hospitalier Franco-Britannique

Levallois-Perret, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Leon Berard

Lyon, France

Location

Related Publications (1)

• Fumet JD, Limagne E, Thibaudin M, Truntzer C, Bertaut A, Rederstorff E, Ghiringhelli F. Precision medicine phase II study evaluating the efficacy of a double immunotherapy by durvalumab and tremelimumab combined with olaparib in patients with solid cancers and carriers of homologous recombination repair genes mutation in response or stable after olaparib treatment. BMC Cancer. 2020 Aug 10;20(1):748. doi: 10.1186/s12885-020-07253-x.

  PMID: 32778095 DERIVED

MeSH Terms

Interventions

olaparib; durvalumab; tremelimumab

Study Officials

• François GHIRINGHELLI

  Centre Georges Francois Leclerc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 20, 2019
• Study Start: February 10, 2020
• Primary Completion (Estimated): August 10, 2027
• Study Completion (Estimated): August 10, 2027
• Last Updated: February 13, 2024

Record last verified: 2024-02

Locations

FR (8)