E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with unresected Stage I/II, lymph-node negative Non-small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Specific type of lung cancer called “Non-Small Cell Lung Cancer” |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung 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 assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS in patients with T1c to T3N0M0 NSCLC |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS for all stage I/II NSCLC patients
To assess the efficacy of durvalumab monotherapy compared to placebo in terms of OS
To further assess the efficacy of durvalumab monotherapy compared to placebo in terms of lung cancer-specific mortality
To further assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS24, TTP, TTDM, and PFS2
To assess the PK of durvalumab
To investigate the immunogenicity of durvalumab
To assess symptoms and health-related quality of life in patients treated with durvalumab monotherapy compared to placebo using the EORTC QLQ-C30
To assess the safety and tolerability profile of durvalumab monotherapy compared to placebo after administration of SBRT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥18 years
2. Histologically or cytologically documented Stage I to II NSCLC, with clinical Stage I/II lymph node-negative (T1 to T3N0M0) disease and planned to receive definitive treatment with SBRT. Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy
3. Completion of SoC SBRT as definitive treatment prior to randomization
4. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) PS of 0, 1, or 2
5. Life expectancy of at least 12 weeks
6. Body weight >30 kg
7. Tumor sample required
8. Adequate organ and marrow function required
9. Patients with central or peripheral lesions are eligible
10. Staging studies must be done within 8 weeks before randomization |
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E.4 | Principal exclusion criteria |
1. Mixed small cell and non-small cell cancer histology
2. History of allogeneic organ transplantation
3. History of another primary malignancy with exceptions
4. History of active primary immunodeficiency
5. Any unresolved toxicity National Cancer Institute (NCI) CTCAE Grade ≥2 from SBRT (Stereotactic Body Radiation Therapy) |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS in patients with T1c to T3N0M0 NSCLC by BICR according to RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
On-study tumor assessments occur 8 weeks after randomization, then every 12 weeks through week 116, then every 16 weeks through 3 years after randomization, then every 6 months thereafter until objective disease progression. |
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E.5.2 | Secondary end point(s) |
PFS in patients with T1 to T3N0M0 NSCLC
OS in patients with T1c to T3N0M0 NSCLC
OS in patients with T1 to T3N0M0 NSCLC
Lung cancer mortality
PFS24, TTP, and TTDM using BICR assessments according to RECIST 1.1
PFS2 using local assessment
Concentration of durvalumab in blood
Presence of ADA for durvalumab
EORTC QLQ-C30: Change in symptoms, functioning, and global health status/quality of life
Safety and tolerability: AEs, physical examinations, vital signs, electrocardiograms, and laboratory findings |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS: from baseline to until death due to any cause
PFS24 - at 24 months following randomization, TTP, TTDM: tumor assessments occur up to every 8 weeks 3 years after randomization, and then every 6 months thereafter
Concentration of durvalumab in blood: at Week 4, 28, 52, 76 and week 100 and 3 Months after completed/discontinued study treatment
ADA: will be collected at Baseline, at Week 28, 52, 76, 100 then months 3 and 6 after completed/discontinued study treatment
EORTC QLQ-C30: Screening, at Baseline, Week 2, 4, 6, 8, 12, 16 and 20 weeks after randomization, then every 8 weeks until 3 years after randomization, then every 6 months until PFS2
Safety and tolerability - from randomization until 3 months after treatment discontinuation |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability
Symptoms and health-related quality of life
Healthcare resource utilization |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Belgium |
Canada |
France |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Spain |
United Kingdom |
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 expected visit/contact of the last patient undergoing the study (last subject last visit) |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |