A Study to Evaluate the Use of Durvalumab in Combination With Platinum-based Chemotherapy Followed by Durvalumab With Olaparib as First-line Treatment in Advanced or Recurrent Endometrial Cancer in Spain

NCT06746116 | Active Not Recruiting Phase 3

• 1 other identifier: D9311L00001
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 24

Brief Summary

This is a phase IIIb, interventional, single arm, multicentre study assessing the safety profile of durvalumab in combination with carboplatin-paclitaxel chemotherapy followed by durvalumab with olaparib as first-line treatment for patients with pMMR aEC as the primary endpoint. The study will include approximately 85 patients distributed in approximately 20 sites in Spain. The planned duration of patient recruitment is approximately 12 months. Each patient will be followed up from screening for 36 months, until end of study period, death, withdrawal from study or loss to follow-up; whichever occurs first. Enrolment will be opened to all eligible patients treated with durvalumab in combination with carboplatin-paclitaxel chemotherapy followed by durvalumab with olaparib as first-line treatment for patients with pMMR aEC. In addition, adequate tumour tissue before study entry, stool and blood sample collected will be required for central analysis to monitor the status of relevant biomarkers.

Conditions

Advanced or Recurrent Endometrial Cancer

Keywords

Durvalumab; Olaparib; pMMR; Endometrial cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients with Adverse Events

  Safety and tolerability will be evaluated in terms of Adverse Events (AEs), Serious AEs (SAEs), and immune-mediated AEs (imAEs)

  Time from enrollment up to at least 90 days after last dose of study treatment

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)

• Objective Response Rate (ORR)

  From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)

• Duration of Response (DoR)

  From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)

• Overall Survival (OS)

  From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)

• Change in EORTC QLQ-C30 score

  From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)

Study Arms (1)

Single Arm

EXPERIMENTAL

Durvalumab + Chemotherapy (chemotherapy phase) plus Durvalumab + Olaparib (maintenence phase)

Drug: Durvalumab + Chemotherapy phase; Drug: Durvalumab + Olaparib phase

Interventions

Durvalumab + Chemotherapy phase DRUG

Durvalumab (IV) with SoC (carboplatin + paclitaxel chemotherapy: patients should receive at least 4, but preferably 6 cycles) every three weeks.

Also known as: Chemotherapy phase

Single Arm

Durvalumab + Olaparib phase DRUG

durvalumab (IV) with olaparib (tablets) every four weeks until progression.

Also known as: Maintenance phase

Single Arm

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease characteristics 3. Histologically confirmed diagnosis of endometrial carcinoma (all histologies, including carcinosarcoma) with archival or recent biopsy available to send at study entry.
• \. Only patients with pMMR tumors are allowed (mismatch repair status determined locally per current clinical practice).
• \. Patients must have endometrial cancer in one of the following categories:
• Newly diagnosed Stage III disease classified by FIGO 2023 with mesurable disease per RECIST 1.1 following surgery or diagnostic biopsy.
• Newly diagnosed Stage IV disease classified by FIGO 2023. Patients with primary cytoreduction without residual disease are allowed.
• Recurrence of disease where the potential for cure by surgery alone or in combination is poor.
• \. Naïve to first-line systemic anti-cancer treatment. For patients with recurrent disease, prior systemic anti-cancer treatment is allowed only if it was administered in the adjuvant setting (for patients with FIGO 2023 stage II, III or IVA) and there is at least 6 months from date of last dose of adjuvant systemic treatment to date of subsequent relapse.
• At least one, but ideally two FFPE tumour sample block must be available and must be suitable for NGS and IHC evaluation by central lab. Preferably from primary endometrial tumor, but also from metastatic site will be allowed if there is no primary tumor block available. Tumor tissue has to have no less than 30% tumoral cell and tumoral area size has to be no less than 0,5cm2.
• Eastern Cooperative Oncology Group (ECOG)/ World Health Organisation (WHO) performance status ≤ 2 at enrolment.
• Note: not more than 20% of patients with ECOG PS2 will be allowed; once this limit is met, additional enrolled patients must have PS \<2.
• Reproductive status 9.Postmenopausal or evidence of nonchildbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of Cycle 1 Day 1 and confirmed prior to treatment on Cycle 1 Day 1. Women will be considered post- menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments, and if they have LH and FSH levels in the post- menopausal range for the institution.
• Women ≥50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago.
• Women who are surgically sterile (ie, bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) are eligible.
• Organ function 10.Adequate organ and bone marrow function, defined as:

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Medical history
• Patients with Grade ≥2 neuropathy may be included only after consultation with the study physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or olaparib may be included only after consultation with the study physician.
• Uterine sarcomas will not be allowed.
• Major surgical procedure (as defined by the investigator) within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. Note: Local surgery of isolated lesions for palliative intent is acceptable or diagnostic staging.
• History of allogenic organ transplantation.
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
• Patients with coeliac disease controlled by diet alone.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (systolic blood pressure \>160 mmHg; diastolic blood pressure \>100 mmHg), unstable angina pectoris, cardiac arrhythmia, interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

Sponsors & Collaborators

• AstraZeneca: lead
• Apices Soluciones S.L.: collaborator

Study Sites (24)

Research Site

A Coruña, 15006, Spain

Location

Research Site

Alicante, 03010, Spain

Location

Research Site

Barakaldo, 48903, Spain

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Córdoba, 14004, Spain

Location

Research Site

El Palmar, 30120, Spain

Location

Research Site

Girona, 17007, Spain

Location

Research Site

L'Hospitalet de Llobregat, 08908, Spain

Location

Research Site

Las Palmas de Gran Canaria, 35016, Spain

Location

Research Site

Madrid, 28034, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Madrid, 28046, Spain

Location

Research Site

Madrid, 28807, Spain

Location

Research Site

Málaga, 29010, Spain

Location

Research Site

Pamplona, 31008, Spain

Location

Research Site

Salamanca, 37007, Spain

Location

Research Site

San Sebastián, 20014, Spain

Location

Research Site

Santander, 39008, Spain

Location

Research Site

Seville, 41013, Spain

Location

Research Site

Valencia, 46009, Spain

Location

Research Site

Valencia, 46010, Spain

Location

Research Site

Valencia, 46026, Spain

Location

Research Site

Vigo, 36312, Spain

Location

Research Site

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

durvalumab

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 Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase IIIb, interventional, single arm, multicentre study.

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: December 24, 2024
• Study Start: December 30, 2024
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

ES (24)