| 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) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | LLT |
| E.1.2 | Classification code | 10025044 |
| E.1.2 | Term | Lung cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 platinum-based doublet, so as to document the benefit of personalizing patient care based on molecular prognostic data. |
|
| 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.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written informed consent (the informed consent document must have been approved by the appropriate Institutional Review Board/Independent Ethics Committee (IRB/IEC). Consent
must be obtained and signed and witnessed PRIOR to any study specific activity.
2. Age ≥ 18 years
3. Able to comply with the protocol, including acceptable candidacy for adjuvant chemotherapy consisting of cisplatin or carboplatin along with paclitaxel, vinorelbine or pemetrexed, according to investigator choice and administered in accordance with the protocol SmPCs and likely compliance with follow-up for anticipated length of study (i.e. 5 years from the initiation of enrollment).
4. Willing to be randomized to chemotherapy.
5. Histologically documented completely resected (R0) Stage I or IIA non-squamous NSCLC per 8th edition, TNM staging system. Mixed histologies that include a squamous cell or small cell or neuroendocrine component are eligible for the study, as long as they contain at least some component that is neither squamous cell, nor small cell nor neuroendocrine. Eligible resections include segmentectomy, lobectomy, bi-lobectomy, sleeve lobectomy, and pneumonectomy.
Resections via wedge resection will not be eligible. Complete resection must also be accompanied by mediastinal lymph
node sampling via mediastinoscopy, bronchoscopic sampling (e.g., endobronchial ultrasound guided biopsy) or surgical sampling. Nodes must be sampled from at least one of the following nodal stations: levels 2, 4, 7, 8, 9 for a right-sided cancer and levels 2, 4, 5, 6, 7, 8, 9 for left-sided cancers.
6. Adequate tissue sample available for 14-Gene Prognostic Assay (paraffin block with tumor occupying at least 25% of the tissue surface area)
7. Life expectancy excluding NSCLC diagnosis ≥ 5 years
8. ECOG performance status 0-1
- Completely healed incisions
For Germany:
9. Women without childbearing potential or
women of childbearing potential who have a negative hCG pregnancy test (either serum or urine) and who agree to meet one of the following criteria from the first administration of chemotherapy, during the treatment and for a period of 6 months following the last administration of chemotherapy:
• Correct use of two reliable contraception methods. This includes every combination of a hormonal implant, transdermal hormonal patch, hormonal vaginal device, hormonal injection or of an intrauterine device or system (IUD/IUS) with a barrier method (condom or occlusive cap),
• True abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception),
• Sexual relationship only with female partners and/or sterile male partners.
10. Men who agree to meet one of the following criteria from the first administration of chemotherapy, during the treatment and for a period of 6 months following the last administration of chemotherapy:
• Correct use of two reliable contraception methods with female partners. This includes every combination of a hormonal implant, transdermal hormonal patch, hormonal vaginal device, hormonal injection or of an intrauterine device or system (IUD/IUS) with a barrier method (condom or occlusive cap),
• True abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception),
• Sexual relationship only with male partners and/or sterile female partners. |
|
| E.4 | Principal exclusion criteria |
1. Final pathologic diagnosis on resected specimen is pure squamous cell, pure small cell or pure neuroendocrine histology, or any combination of only these three histologies
2. Evidence of greater than stage I or IIA pathologic staging per the 8th edition of the TNM staging system, including loco-regional regional (hilar) or mediastinal lymph node involvement or nodal enlargement that has not been biopsied, or
of distant metastatic disease (lesions that have been biopsy-proven or that are suspicious on brain MRI and/or PET scan)
3. Evidence of incomplete resection, including positive resection margins, additional suspect nodules
4. Pregnant or lactating women
5. n/a for Germany
6. Active infection, either systemic or at site of primary resection
7. Any pre-operative systemic chemotherapy or treatment with an anti-cancer agent within 5 years prior to study enrollment
8. Radiotherapy to the chest in the immediate pre- or post-operative period.
9. Malignancies other than the current NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated locally with curative intent, ductal carcinoma in situ treated surgically with curative intent
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 (see above) such as neurologic or metabolic dysfunction or physical examination finding giving reasonable suspicion of a disease or condition that contraindicates the use of systemic cytotoxic chemotherapy or puts the patient at high risk for treatment related complications. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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.
|
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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) |
|
| 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 |
| United States |
| France |
| Germany |
| Spain |
|
| 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
|
|
| 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 |
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