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Durvalumab Treatment in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer Patients.

NCT03737643

Description:

This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.

Related Conditions:
  • Fallopian Tube Carcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Malignant Ovarian Clear Cell Tumor
  • Ovarian Carcinosarcoma
  • Ovarian Endometrioid Tumor
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab Treatment in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer Patients.
  • Official Title: A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).

Clinical Trial IDs

  • ORG STUDY ID: D081RC00001
  • SECONDARY ID: 2017-004632-11
  • NCT ID: NCT03737643

Conditions

  • Advanced Ovarian Cancer

Interventions

DrugSynonymsArms
BevacizumabArm 1
DurvalumabArm 2
OlaparibArm 3
Placebo olaparibArm 1
Durvalumab placeboArm 1
Carboplatin+PaclitaxelArm 1

Purpose

This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.

Detailed Description

      Eligible patients will be those patients with newly diagnosed, histologically confirmed
      advanced (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] Stage III-IV)
      ovarian, primary peritoneal cancer and/or fallopian-tube cancer. All patients should be
      candidates for cytoreductive surgery which could be conducted as immediate upfront primary
      surgery following diagnosis or can be conducted after initiation of platinum based
      neoadjuvant chemotherapy. All patients should be eligible to start first line platinum based
      chemotherapy in combination with bevacizumab.

      The study aims to evaluate the efficacy and safety of standard of care (SoC) platinum-based
      chemotherapy and bevacizumab followed by maintenance bevacizumab either as monotherapy, or in
      combination with durvalumab, or in combination with durvalumab and olaparib. Therefore, this
      study aims to see which combination allows patients to live longer without the cancer coming
      back or getting worse. The study is also looking to see which combination makes patients live
      longer and how the treatment and the cancer affects their quality of life.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1Active ComparatorPlatinum-based chemotherapy in combination with bevacizumab and durvalumab placebo (saline IV infusion) followed by maintenance bevacizumab, durvalumab placebo (saline IV infusion) and olaparib placebo (tablets).
  • Bevacizumab
  • Placebo olaparib
  • Durvalumab placebo
  • Carboplatin+Paclitaxel
Arm 2ExperimentalPlatinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo.
  • Bevacizumab
  • Durvalumab
  • Placebo olaparib
  • Carboplatin+Paclitaxel
Arm 3ExperimentalPlatinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib.
  • Bevacizumab
  • Durvalumab
  • Olaparib
  • Carboplatin+Paclitaxel
tBRCAm cohortExperimentalPlatinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib. Bevacizumab is optional according to local practice.
  • Bevacizumab
  • Durvalumab
  • Olaparib
  • Carboplatin+Paclitaxel

Eligibility Criteria

        Key Inclusion Criteria:

        Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV)
        high grade epithelial ovarian cancer including high grade serious, high grade endometriod,
        clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or
        fallopian-tube cancer

          -  Patients must be aged ≥18 years of age. For patients enrolled in Japan that are aged
             <20 year

          -  All patients should be candidates for cytoreductive surgery either: upfront primary
             surgery OR plan to undergo chemotherapy with interval debulking surgery

          -  Evidence of presence or absence of BRCA1/2 mutation in tumour tissue

          -  Mandatory provision of tumour sample for centralised tBRCA testing

          -  ECOG performance status 0-1

          -  Patients must have preserved organ and bone marrow function

          -  Postmenopausal or evidence of non-childbearing status for women of childbearing
             potential: negative urine or serum pregnancy test

        Key Exclusion Criteria:

        Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous
        histology

          -  Prior systemic anti-cancer therapy for ovarian cancer

          -  Inability to determine the presence or absence of a deleterious or suspected
             deleterious BRCA mutation

          -  Prior treatment with PARP inhibitor or immune mediated therapy

          -  Planned intraperitoneal cytotoxic chemotherapy

          -  Active or prior documented autoimmune or inflammatory disorders

          -  Patients considered a poor medical risk due to a serious, uncontrolled intercurrent
             illness

          -  Clinically significant cardiovascular disease

          -  Patients with known brain metastases

          -  History of another primary malignancy except for:

               -  Malignancy treated with curative intent and with no known active disease ≥5 years
                  before the first dose of study treatment and of low potential risk for recurrence
                  (patients who have received prior adjuvant chemotherapy for early stage breast
                  cancer may be eligible, provided that it was completed ≥3 years prior to
                  registration, and that the patient remains free of recurrent or metastatic
                  disease)

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease

               -  Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2

          -  Persistent toxicities CTCAE Grade >2 caused by previous cancer therapy

          -  Patients with a known hypersensitivity to olaparib, durvalumab or any of the
             excipients of these products and to the combination/comparator agents

          -  Breast feeding women
      
Maximum Eligible Age:150 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) - in non-tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:Defined as time from randomisation to first progression by investigator assessment using modified RECIST 1.1 or death (by any cause in the absence of progression)

Secondary Outcome Measures

Measure:Overall Survival (OS) - in non-tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:Defined as the time from randomisation to death due to any cause
Measure:Second Progression (PFS2) - in non-tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:Defined as time from randomisation to second progression by investigator assessment of radiological progression, symptomatic progression or death (by any cause in the absence of progression)
Measure:Health-related quality of life - in non-tBRCAm patients
Time Frame:Approximately 3 years
Safety Issue:
Description:Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30
Measure:pathological Complete Response (pCR) - in non-tBRCAm patients
Time Frame:Approximately 3 months after randomisation
Safety Issue:
Description:Defined as the proportion of patients with pCR in patients undergoing IDS
Measure:The pharmacokinetics (PK) and immunogenicity of durvalumab and olaparib as determined by peak concentration - in non-tBRCAm patients
Time Frame:Approximately 18 months
Safety Issue:
Description:Determination of durvalumab concentration in serum and olaparib concentration in plasma in a subset of patients
Measure:Objective Response Rate (ORR) - in non-tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:Defined as the number (%) of patients with at least one investigator-assessed visit response of CR or PR as per RECIST 1.1
Measure:Duration of response (DoR) - in non-tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:Defined as the time form the date of first documented response (CR/PR) until the first progression or death in the absence of disease progression
Measure:Time to first subsequent therapy (TFST) - in non-tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:Time elapsed from randomisation to first subsequent therapy or death
Measure:Time to second subsequent therapy (TSST) - in non-tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:Time elapsed from randomisation to second subsequent therapy or death
Measure:Time to discontinuation or death (TDT) - in non-tBRCAm patients
Time Frame:Approximately 30 months
Safety Issue:
Description:Time elapsed from randomisation to study treatment discontinuation or death
Measure:PFS - in tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Measure:PFS2 - in tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Measure:ORR - in tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Measure:ORR pre-surgery in IDS group - in tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Measure:duration of response (DoR) - in tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Measure:Time to first subsequent therapy (TFST) - in tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Measure:Time to second subsequent therapy (TSST) - in tBRCAm patients
Time Frame:Approximately 6 years
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Measure:Time to discontinuation or death (TDT) - in tBRCAm patients
Time Frame:Approximately 30 months
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients
Measure:Health-related quality of life - in tBRCAm patients
Time Frame:Approximately 3 years
Safety Issue:
Description:Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30
Measure:Proportion of patients with pCR in patients undergoing IDS - in tBRCAm patients
Time Frame:Approximately 3 months after cohort allocation
Safety Issue:
Description:To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Advanced Ovarian Cancer
  • Ovarian neoplasms

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