UTOLA: UTerin OLAparib

NCT03745950 | Completed Phase 2 DMC

• 1 other identifier: GINECO-EN-104b
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 36

Brief Summary

This is a phase IIB, national, randomized, double-blinded, comparative, multi-center study, to assess the efficacy of Olaparib as maintenance after a platinum based chemotherapy in patients with Advanced or metastatic endometrial cancer

Conditions

Endometrial Carcinoma

Keywords

Maintenance therapy; Olaparib; Randomized, double blinded; P53 and MMR Immunohistochemistry; Phase II; progression-free survival

Outcome Measures

Primary Outcomes (1)

• Efficacy: Progression free survival (PFS1) according to modified Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) of Olaparib maintenance after a platinum based chemotherapy in patients with advanced or metastatic endometrial cancer

  An average of 36 months

Secondary Outcomes (14)

• To determine time from randomization until death from any cause

  To be assessed around 73 months

• To determine time from randomization to efficacy by progression free survival

  To be assessed around 36 months

• To determine time from response rate according to IHC P53, MMR, NGS BRCA/HRD, MSI

  To be assessed around 36 months

• To determine the overall response rate ORR

  To be assessed around 30 months

• To determine time from randomization to first and second subsequent therapy (TFST, TSST)

  To be assessed around 36 months

Study Arms (2)

Olaparib

EXPERIMENTAL

The Olaparib arm : Patients will be administrated the randomized study treatment tablets orally at a dose of 300 mg twice daily until objective radiological disease progression as per RECIST (Response evaluation criteria in solid tumors) as assessed by the investigator, or unacceptable toxicity

Drug: Olaparib Oral Capsule

Placebo

PLACEBO COMPARATOR

The placebo arm : Patients will be administrated the randomized study treatment tablets orally at a dose of 300 mg twice daily until objective radiological disease progression as per RECIST as assessed by the investigator, or unacceptable toxicity

Drug: Placebo oral capsule

Interventions

Olaparib Oral Capsule DRUG

\- Olaparib will be administrated by oral at dose of 300 mg twice daily during the induction period and in maintenance

Olaparib

Placebo oral capsule DRUG

\- Placebo will be administrated by oral at dose of 300 mg twice daily during the induction period and in maintenance

Placebo

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female Patient ≥18 years at the day of consenting to the study
• Provision of informed consent prior to any study specific procedures
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Patient with advanced/metastatic endometrial cancer not candidate to a curative treatment with surgery or radiotherapy
• Patients who have completed prior to randomization one Platine based chemotherapy for advanced disease after 6 cycles of chemotherapy (at least 4 cycles of platine). Patients must have a measurable disease according RECIST 1-1 at the initiation of the chemotherapy (cf. appendix 3)
• Patients must be prior to randomization without evidence of disease (NED) or in complete response (CR) or partial response (PR) or stable disease from the chemotherapy
• Patient should have been tested biolology for IHC : P53 and MMR within two weeks before the randomisation and (NGS; BRCA/HRD) within 3 months after the randomisation
• Patients could have been previously treated with Hormone-therapy
• Adjuvant chemotherapy or local radio-chemotherapy is allowed (with a delay of at least of 12 months). First recurrence at least 12 months after a loco-regional treatment.
• Patients pay have received external beam +/- vaginal brachytherapy
• All histologic and molecular subtypes of endometrial carcinoma will be included (including mixte histology), except carcinosarcoma, neuro-endocrine and small cells carcinoma.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥10.0 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelet count ≥100 x 109/L

You may not qualify if:

• Patients with carcinosarcoma, neuro-endocrine and small cells histologies
• Patients who have previously received more than 1 line of chemotherapy for advanced/metastatic endometrial cancer
• Patients with a localized advanced disease that could be treated by surgery
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS)
• Patients with myelodysplastic syndrome/acute myeloid leukemia history or with features suggestive of MDS/AML.
• Patients receiving radiotherapy within 6 weeks prior to study treatment.
• Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• Any previous treatment with PARP inhibitor, including olaparib.
• Clinically significant (e.g. active) cardiovascular disease, uncontrolled high blood pressure
• Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.
• History or evidence of hemorrhagic disorders within 6 months prior to randomization
• Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead

Study Sites (36)

ICO Paul Papin

Angers, France

Location

Institut du cancer Avignon-Provence

Avignon, France

Location

CHRU Jean Minjoz

Besançon, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, France

Location

Chu Dijon

Dijon, 21000, France

Location

Centre Georges François Leclerc

Dijon, France

Location

Institut Daniel Hollard - GHM de Grenoble

Grenoble, France

Location

Institut inter-régionaL de Cancérologie - Centre Jean Bernard - Clinique Victor Hugo

Le Mans, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Hôpital Saint-Joseph

Marseille, France

Location

Centre Hospitalier de Mont-De-Marsan

Mont-de-Marsan, France

Location

ICM Val d'Aurelle

Montpellier, France

Location

Centre Azuréen de Cancérologie

Mougins, France

Location

Centre d'Oncologie de Gentilly

Nancy, France

Location

Hôpital Privé du Confluent SAS

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut de Cancérologie du Gard - CHU de Nîmes

Nîmes, France

Location

CHR d'Orléans

Orléans, France

Location

Groupe Hospitalier Diaconesses Croix Saint-Simon

Paris, France

Location

Hôpital Cochin

Paris, France

Location

Institut Curie - Hopital Claudius Régaud

Paris, France

Location

Polyclinique Francheville

Périgueux, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Centre CARIO - HPCA

Plérin, France

Location

CHU de Poitiers - Hôpital de la Milétrie

Poitiers, France

Location

Centre Henri Becquerel

Rouen, France

Location

ICO Centre René Gauducheau

Saint-Herblain, France

Location

CHU Saint Etienne - Pôle de Cancérologie

Saint-Priest-en-Jarez, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, France

Location

Institut Claudius Régaud

Toulouse, France

Location

Institut de Cancérologie de Lorraine - Centre Alexis Vautrin

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Florence JOLY

  GINECO - Centre François Baclesse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Olaparib vs placebo

Study Record Dates

• First Submitted: October 31, 2018
• First Posted: November 19, 2018
• Study Start: February 1, 2019
• Primary Completion: May 22, 2023
• Study Completion: September 24, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-12

Locations

FR (36)