A Randomized Prospective Trial of Adjuvant Chemotherapy in Patients with Completely Resected Stage I or IIA Non-Squamous Non-Small Cell Lung Cancer Identified as High or Intermediate Risk by a 14-Gene Prognostic Assay

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Razor Genomics Inc., Intergroupe Francophone De Cancerologie Thoracique

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Nov 2020 → ongoing

Decision date (initial)

2024-03-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511185-37-00

EudraCT number

2013-001494-24

ClinicalTrials.gov

NCT01817192

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective of this study is to compare 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 either randomized to observation or randomized to and are willing to initiate adjuvant therapy with four cycles of a standard NSCLC platinum-based doublet (i.e., mITT population), so as to document the benefit of personalizing patient care based on molecular prognostic data.

Secondary objectives 3

1. To compare DFS in patients randomized to each study arm without regard to actual initiation of chemotherapy (i.e., ITT population), and in patients randomized to each study arm who comply with Observation and Chemotherapy Arm assignments and who receive at least half of the intended chemotherapy course if randomized to that Arm (i.e., PP population).
2. To compare OS and TTR in patients randomized to each study arm.
3. 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.

Conditions and MedDRA coding

Completely resected stage I or IIA non-squamous non-small cell lung cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
2. Age ≥ 18 years
3. Able to comply with the protocol, including acceptable candidacy for adjuvant chemotherapy according to local institutional standards 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 (See Appendix A). 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 the 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
9. Women of childbearing potential: - who are practicing true abstinence from sexual intercourse (periodic abstinence and withdrawal are not acceptable), - who have sexual relationships with female partners only and/or with sterile male partners, or women of childbearing potential and sexually active with fertile male partner must have a negative pregnancy test during screening and agree to use reliable methods of contraception from the time of screening, during the study and for a period of 6 months following the last administration of study medication. The following methods of contraception are acceptable: 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), women without childbearing potential defined as follows: at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy, hysterectomy or uterine agenesis, ≥ 50 years and in postmenopausal state > 1 year, or < 50 years and in postmenopausal state > 1 year with serum FSH > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening.
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 study chemotherapy: - Correct use of two reliable contraception methods with female partners. This include 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.
11. Patient should be covered by a national health insurance (only for patient enrolled in France).

Exclusion criteria 13

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. Active infection, either systemic or at site of primary resection
6. Any pre-operative systemic chemotherapy or treatment with an anti-cancer agent within 5 years prior to study enrollment.
7. Radiotherapy to the chest in the immediate pre- or post-operative period.
8. Malignancies other than the current NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, non-melanoma cell skin cancer, localized prostate cancer treated locally with curative intent, ductal carcinoma in situ treated surgically with curative intent.
9. Treatment with any investigational drug or participation in another clinical trial within 28 days prior to enrollment.
10. Known hypersensitivity to any of the study treatment agents.
11. 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.
12. Wound dehiscence or infection.
13. Patient who is subject to legal protection or who is unable to express his will (only for patient enrolled in France).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy analysis is based on the duration of DFS in patients determined to be at High- and Intermediate Risk by the 14-Gene Prognostic Assay. DFS is defined as the time from randomization to disease recurrence, or death from any cause. Patients without events at the time of analysis will be censored at their last known event-free date. The primary efficacy analysis will be based on the modified intent-to-treat (mITT) population.

Secondary endpoints 4

1. The key secondary efficacy analysis is based on the duration of DFS in patients in the standard intent-to-treat (ITT) population. Patients without events at the time of analysis will be censored at their last known event-free date. An additional key secondary efficacy analysis is based on the duration of DFS in the per-protocol (PP) population.
2. Additional Secondary analysis: OS in patients determined to be at High or Intermediate Risk by the 14-Gene Prognostic Assay 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.
3. Time to recurrence (TTR) in patients determined to be at High or Intermediate Risk by the 14-Gene Prognostic Assay is defined as length of time from randomization until documented disease recurrence, with death as a competing risk. For TTR, recurrences that are first diagnosed at time of death will be treated as recurrences at date of death. Patients without documented recurrence will be censored at their last documented FU. These analyses will be undertaken for mITT, ITT and PP populations.
4. An additional secondary endpoint of the trial is to compare OS and, to the degree possible, DFS and TTR in patients identified by the 14-Gene Prognostic Assay as High or Intermediate risk stage I or IIA non-squamous NSCLC randomized to observation with patients identified by the 14-Gene Prognostic Assay as Low-Risk stage I or IIA non-squamous NSCLC.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Razor Genomics Inc.

Sponsor organisation

Razor Genomics Inc.

Address

111 10th Avenue South Suite 102 Room 123

City

Nashville

Postcode

37203-3821

Country

United States

Scientific contact point

Organisation

Razor Genomics Inc.

Contact name

Legal representative

Public contact point

Organisation

Razor Genomics Inc.

Contact name

Legal representative

Third parties 3

Intergroupe Francophone De Cancerologie Thoracique

Sponsor organisation

Intergroupe Francophone De Cancerologie Thoracique

Address

10 Rue De La Grange Bateliere

City

Paris

Postcode

75009

Country

France

Sponsor responsibilities

Article 77 compliance

Razor Genomics Inc.

Contact point sponsor

Razor Genomics Inc.

Article 77 implementation

Razor Genomics Inc.

Locations

2 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications