E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Cancer in the lining of the uterus or womb |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014733 |
E.1.2 | Term | Endometrial cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab (Arm B) compared to platinum-based chemotherapy alone (Arm A) by assessment of progression free survival (PFS), in patients with newly diagnosed advanced or recurrent endometrial cancer |
|
E.2.2 | Secondary objectives of the trial |
-To determine the efficacy of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab (Arm B) or durvalumab with olaparib (Arm C) when compared to platinum-based chemotherapy alone (ArmA) in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of: PFS (Arm C vs A only), PFS2, OS, ORR, DoR, TFST, TSST and TDT.
- To characterise the PK and immunogenicity of durvalumab and durvalumab in combination with olaparib.
- To evaluate the safety and tolerability of durvalumab in combination with platinum-based chemotherapy followed by maintenance durvalumab or durvalumab with olaparib compared to platinum-based chemotherapy alone.
- To determine effects on symptoms, functioning and overall health related quality of life (HRQoL) of durvalumab in combination with platinum-based chemotherapy followed by maintenance durvalumab or durvalumab with olaparib when compared to platinum-based chemotherapy alone. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥18 years at the time of screening and female.
- Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed.
- Patient must have endometrial cancer in one of the following categories:
a) Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy),
b) Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy)
c) Recurrence of disease (measurable or non-measurable disease per RECIST 1.1) 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 only, prior chemotherapy is allowed only if it was administered in the adjuvant setting (as part of the upfront/adjuvant anti-cancer treatment, which may be concurrent or followed with chemoradiation) and there is at least 12 months from date of last dose of chemotherapy administered to date of subsequent relapse.
- FPPE tumor sample must be available for MMR evaluation.
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment. |
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E.4 | Principal exclusion criteria |
- History of leptomeningeal carcinomatosis.
- Brain metastases or spinal cord compression.
- Prior treatment with PARP inhibitors.
- Prior immune-mediated therapy including other anti-CTLA-4, anti-PD-1, anti-PD-L1 or anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines |
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E.5 End points |
E.5.1 | Primary end point(s) |
- PFS (per RECIST 1.1 as assessed by investigator) is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- randomisation until the date of objective disease progression or death |
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E.5.2 | Secondary end point(s) |
- PFS2: Second progression-free survival is defined as the time from randomisation to the earliest of progression event subsequent to first subsequent therapy (assessed by the investigator per local standard clinical practice and may involve any of the following: objective radiological imaging, symptomatic progression), or death due to any cause.
- OS: Overall survival is defined as the time from the date of randomisation until death due to any cause.
- ORR: Objective response rate is the proportion of patients with measurable disease at baseline who have confirmed complete response (CR) or partial response (PR), as determined by the investigator at local site.
- DoR: Duration of response is time from the date of first documented response (subsequently confirmed) until date of documented progression or death in the absence of disease progression, as determined by the investigator at local site.
- TFST: Time to first subsequent therapy or death is time from randomisation to the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment or death due to any cause.
- TSST: Time to second subsequent therapy or death is time from randomisation to the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment or death due to any cause.
- TDT: Time to study treatment discontinuation or death is time from randomisation to the earlier of the date of study treatment discontinuation or death.
- Serum concentrations of durvalumab
- Anti-drug antibodies (ADA) to durvalumab
- Safety and tolerability will be evaluated in terms of AEs/serious AEs (SAEs), physical examination, vital signs including blood pressure, pulse, clinical laboratory including clinical chemistry/haematology parameters, and ECG |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- PFS2: The earliest of progression event subsequent to first subsequent therapy, or death due to any cause.
- OS: Date of death
- ORR: First objective response (complete or partial response)
- DoR: First documented response until date of progression or death, as determined by the investigator at local site
- TFST: First subsequent anti-cancer therapy after discontinuation of randomised treatment or death
- TSST: Second subsequent anti-cancer therapy after discontinuation of first subsequent treatment or death
- TDT: Time from randomisation to the earlier of the date of study treatment discontinuation or death.
- Durvalumab PK: Cycle 5 day1, Cycle 9 day1
- Durvalumab ADA: Cycle1 day1 Pre-dose, Cycle 5 day1, Cycle 9 day1
- Safety and tolerability: throughout the course of the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 64 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
China |
Colombia |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Russian Federation |
Singapore |
United States |
Belgium |
Estonia |
Germany |
Greece |
Italy |
Lithuania |
Netherlands |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit/contact of the last patient at the data cut-off time of the final
OS analysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |