E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Completely resected stage I or IIA non-squamous non-small cell lung cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029517 |
E.1.2 | Term | Non-small cell lung cancer stage I |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029518 |
E.1.2 | Term | Non-small cell lung cancer stage II |
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 |
The primary objective of this study is to compare disease-free survival (DFS) in patients with completely resected (R0), stage I or IIA non-squamous NSCLC who are found to be at high or intermediate risk by the 14-Gene Prognostic Assay and who are subsequently randomized to either observation or adjuvant therapy with four cycles of a standard NSCLC cisplatin-based doublet, so as to document the benefit of personalizing patient care based on molecular prognostic data. |
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E.2.2 | Secondary objectives of the trial |
1. To compare overall survival (OS) in patients randomized to each study arm. 2. To further document the previously verified separation of survival curves among high- and low-risk patients identified by the 14-Gene Prognostic Assay in this prospective cohort of stage I or IIA non- squamous NSCLC patients. 3. To collect fresh frozen and formalin-fixed paraffin-embedded (FFPE) tissue specimens from a subset of patients with consent for full clinical annotation for future analysis of molecular and genetic correlates of disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent 2. Age ≥ 18 years 3. Able to comply with the protocol, including acceptable candidacy for adjuvant chemotherapy and likely compliance with follow-up for anticipated length of study (i.e. 5 years from the initiation of enrollment). 4. Histologically documented completely resected (R0) Stage I or IIA non-squamous NSCLC (per 8th edition, TNM staging system) 5. Adequate tissue sample for the 14-Gene Prognostic Assay 6. Life expectancy excluding NSCLC diagnosis ≥ 5 years 7. ECOG performance status 0-1 8. Adequate haematological function: • Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 AND • Platelet count ≥ 100000 cells/mm3 AND • Haemoglobin ≥ 9 g/dL (may be transfused to maintain or exceed this level) 9. Adequate liver function: • Total bilirubin < 1.5 x upper limit of normal (ULN) AND • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN 10. Adequate renal function, with Serum creatinine ≤ 1.5 x ULN 11. Completely healed incisions |
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E.4 | Principal exclusion criteria |
1. Final pathologic diagnosis of pure squamous cell, pure small cell, or pure neuroendocrine histology, or any combination of only these three histologies 2. Evidence of greater than stage IIA pathologic staging 3. Evidence of incomplete resection 4. Pregnant or lactating women 5. Unwilling to use an effective means of contraception 6. Active infection, either systemic or at site of primary resection 7. Systemic chemotherapy or anti-cancer agent within 5 years prior to enrollment 8. Any pre- or post-operative radiotherapy 9. Malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated CIS of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically, ductal carcinoma in situ treated surgically 10. Treatment with any investigational drug or participation in another clinical trial within 28 days prior to enrollment 11. Known hypersensitivity to any of the study treatment agents 12. Evidence of any other disease including infection that 13. contraindicates the use of systemic cytotoxic chemotherapy or puts the patient at high risk for treatment related complications |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the duration of disease-free survival (DFS) in patients determined to be at High- and Intermediate Risk by the 14-gene Prognostic Assay. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DFS is defined as the time from randomization to disease recurrence, new primary lung cancer, or death from any cause. Patients without events at the end of the analysis will be censored at their last known event-free date. |
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E.5.2 | Secondary end point(s) |
a. Key Secondary Endpoint: Overall survival (OS) in patients determined to be at High or Intermediate Risk by the 14-gene Prognostic Assay. b. An additional secondary endpoint of the trial is to compare disease-free and overall survival in patients identified by the 14-Gene Prognostic Assay as high-risk stage I or IIA non-squamous NSCLC randomized to observation with patients identified by the14-Gene Prognostic Assay as low-risk stage I or IIA non-squamous NSCLC. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a. OS is defined to be the time from randomization to death. Patients alive at the end of the analysis will be censored at their last known alive date.
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Observation (without chemotherapy) |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
France |
Germany |
Spain |
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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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |