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.
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
Interventions
Drug | Synonyms | Arms |
---|
Bevacizumab | | Arm 1 |
Durvalumab | | Arm 2 |
Olaparib | | Arm 3 |
Placebo olaparib | | Arm 1 |
Durvalumab placebo | | Arm 1 |
Carboplatin+Paclitaxel | | Arm 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
Name | Type | Description | Interventions |
---|
Arm 1 | Active Comparator | Platinum-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 2 | Experimental | Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib placebo. | - Bevacizumab
- Durvalumab
- Placebo olaparib
- Carboplatin+Paclitaxel
|
Arm 3 | Experimental | Platinum-based chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab and olaparib. | - Bevacizumab
- Durvalumab
- Olaparib
- Carboplatin+Paclitaxel
|
tBRCAm cohort | Experimental | Platinum-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: | 130 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression Free Survival (PFS) - in non-tBRCA HRD positive patients |
Time Frame: | Approximately 4 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: | Progression Free Survival (PFS) - in non-tBRCAm patients |
Time Frame: | Approximately 4 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) |
Measure: | Overall Survival (OS) - in non-tBRCA HRD positive patients and in all non-tBRCA patients |
Time Frame: | Approximately 7 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 7 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 4 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 4 years |
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 4 years |
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 4 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 4 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 7 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 7 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 4 years |
Safety Issue: | |
Description: | Time elapsed from randomisation to study treatment discontinuation or death |
Measure: | PFS - in tBRCAm patients |
Time Frame: | Approximately 4 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 7 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 4 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 4 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 4 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 7 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 7 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 4 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: | Health-related quality of life - in tBRCAm patients |
Time Frame: | Approximately 4 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 4 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 |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | AstraZeneca |
Trial Keywords
- Advanced Ovarian Cancer
- Ovarian neoplasms
Last Updated
August 17, 2021