E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient with FIGO Stages IB2 to IIB Node+ and IIIA to IVA with any node. Patients must not have previously received any definitive surgical, radiation, or systemic therapy for cervical cancer and must be immunotherapy-naïve. |
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E.1.1.1 | Medical condition in easily understood language |
Treatment naive patients with cervical cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 assess the efficacy of durvalumab + SoC CCRT compared with placebo + SoC CCRT in terms of Progression-Free Survival (PFS) |
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E.2.2 | Secondary objectives of the trial |
1. To further assess the efficacy of durvalumab + SoC CCRT compared with placebo + SoC CCRT in terms of overall survival(OS), PFS in PD-L1 positive patients, objective response rate(ORR), complete response (CR) rate, and DoR in Patients with CR.
2. To assess the effect of durvalumab + SoC CCRT compared with placebo + SoC CCRT on the incidence of local progression, distant disease progression, and secondary malignancy as the first documented progression event.
3. To assess disease-related symptoms and health-related quality of life (HRQoL) in patients with cervical cancer treated with durvalumab + SoC CCRT compared with placebo + SoC CCRT using the core quality of life questionnaire (EORTC QLQ-C30) and core quality of life questionnaire cervical cancer module (CX24).
4. To assess the PK of durvalumab when in combination with CCRT.
5. To investigate the immunogenicity of durvalumab when in combination with CCRT. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female
2. Aged at least 18 years
3. Documented evidence of cervical adenocarcinoma or squamous carcinoma FIGO Stage IB2-IIB Node positive or IIIA-IVA any node
4. No prior chemotherapy or radiotherapy for cervical cancer
5. WHO/ECOG performance status of 0-1
6. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion at baseline. |
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E.4 | Principal exclusion criteria |
1. Diagnosis of small cell (neuroendocrine) histology cervical cancer
2. Intent to administer a fertility-sparing treatment regimen
3. Undergone a previous hysterectomy
4. Evidence of metastatic disease per RECIST 1.1 including lymph nodes ≥15 mm (short axis) above the L1 cephalad body or outside the planned radiation field.
5. History of allogeneic organ transplantation
6. Active or prior documented autoimmune or inflammatory disorders
7. Uncontrolled intercurrent illness
8. History of another primary malignancy and active primary immunodeficiency |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) per RECIST 1.1 or histopathologic confirmation of local tumor progression |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Estimated to be from the time of randomization up to 4.5 years |
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E.5.2 | Secondary end point(s) |
1. Overall Survival (OS)
2. Objective Response Rate (ORR)
3. Complete Response (CR) rate
4. Duration of Response (DoR) in patients with a Complete Response (CR)
5. Health-related quality of life (HRQoL) measured by EORTC QLQ-C30 and core quality of life questionnaire cervical cancer module (CX24).
6. PK and ADA of durvalumab when in combination with CCRT
7. Progression-free Survival(PFS) in PD-L1 high patients |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. During treatment and through to study completion, up to approximately 5 years.
2. During treatment and through to database lock, up to approximately 4.5 years.
3. During treatment and through to database lock, up to approximately 5 months.
4. During treatment and through to database lock, up to approximately 4.5 years.
5. During treatment and through to database lock, up to approximately 4.5 years.
6. During treatment and through to 180 days after last dose of investigational product.
7. During treatment and through to database lock, up to approximately 4.5 years. |
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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 | No |
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 | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Brazil |
Chile |
China |
Hungary |
India |
Japan |
Korea, Republic of |
Mexico |
Peru |
Philippines |
Poland |
Russian Federation |
South Africa |
Taiwan |
United States |
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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 Subject Last Visit(LSLV) |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |