Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Adjuvant Chemotherapy in Patients With Intermediate or High Risk Stage I or Stage IIA Non-squamous Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01817192
Recruitment Status : Recruiting
First Posted : March 25, 2013
Last Update Posted : June 29, 2021
Sponsor:
Collaborator:
Encore Clinical
Information provided by (Responsible Party):
Encore Clinical ( Razor Genomics )

Tracking Information
First Submitted Date  ICMJE March 16, 2013
First Posted Date  ICMJE March 25, 2013
Last Update Posted Date June 29, 2021
Actual Study Start Date  ICMJE September 11, 2020
Estimated Primary Completion Date May 15, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
Disease-Free Survival [ Time Frame: 5 years ]
To compare Disease Free Survival in patients with resected, stage I or IIA non-squamous NSCLC found to be at intermediate or high risk by the 14-Gene Prognostic Assay randomized to either observation or adjuvant therapy with 4 cycles of a cisplatin-based doublet.
Original Primary Outcome Measures  ICMJE
 (submitted: March 22, 2013)
Overall Survival [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
Overall Survival [ Time Frame: 5 years ]
To compare Overall Survival in patients randomized to each study arm. To further document the previously verified separation of the 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2013)
Disease-Free Survival [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjuvant Chemotherapy in Patients With Intermediate or High Risk Stage I or Stage IIA Non-squamous Non-Small Cell Lung Cancer
Official Title  ICMJE 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 Intermediate or High Risk by a 14-Gene Prognostic Assay
Brief Summary The optimal treatment for Stage I or Stage IIA non-small cell lung cancer (NSCLC) remains controversial. Radiographic surveillance alone has been recommended for stage I and stage IIA patients after the tumor is removed surgically from the lung, and this standard has been based on the fact that no previous clinical trial has demonstrated a benefit for Stage I or Stage IIA NSCLC patients who receive post-operative chemotherapy. These patients, however, have a substantial risk of death within five years after operation, ranging from approximately 30% to 45%, largely due to metastatic disease that is present immediately after surgery but that is undetectable by conventional methods. Some leading organizations therefore currently recommend post-operative chemotherapy as an alternative standard of care in Stage I or Stage IIA NSCLC patients who are considered to be at particularly high-risk. Up until now, however, there has not been a well-validated means to identify stage I and stage IIA NSCLC patients at high risk of death within five years after operation. A new prognostic tool, a 14-Gene Prognostic Assay, which has been validated and definitively demonstrated in large scale studies to identify intermediate and high-risk stage I or Stage IIA patients with non-squamous NSCLC, is now available to all clinicians through a CLIA-certified laboratory. It is therefore now possible to compare the outcomes of patients randomly assigned to one or the other of these competing standards of care.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description:
Results of 14-Gene prognostic assay will not be revealed to the patient. Low risk patients will be observed, intermediate and high risk patients will be randomized to observation or four cycles of a cisplatin-based doublet therapy.
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Adjuvant Chemotherapy
    Patients who have undergone complete resection of NSCLC that has been documented histologically to be non-squamous and that is pathological Stage I or IIA, will undergo testing with the 14-Gene Prognostic Assay. Patients determined to be intermediate or high risk and who meet all eligibility criteria will be randomized either to observation or to four cycles of adjuvant therapy with a standard NSCLC cisplatin-based doublet.
  • Other: Radiographic surveillance
    Serial radiographic surveillance is a current standard of care for Stage I or Stage IIA lung cancer. All intermediate or high risk patients randomized to observation or chemotherapy will have routine CT Scans at 6 month intervals until 5 years after enrollment and at yearly intervals thereafter until the end of the study period.
  • Other: 14-Gene Prognostic Assay
    This CLIA-approved assay is a standard tool that is now available to all clinicians to improve the prognostic evaluation of patients after resection of Stage I or Stage IIA non-squamous NSCLC. It will be performed on tumor specimens for patients who are potentially eligible for this study. Patients identified through the assay as intermediate or high-risk will be randomized to either adjuvant chemotherapy or observation.
Study Arms  ICMJE
  • Active Comparator: Observation
    Post-operative observation of Stage I or Stage IIA non squamous non-small cell lunger cancer with Radiographic Surveillance is a current standard of care. Patients identified as low risk will be observation. Those patients identified as intermediate or high-risk by the 14-Gene Prognostic Assay will be randomized either to this arm or the Adjuvant Chemotherapy Arm.
    Interventions:
    • Other: Radiographic surveillance
    • Other: 14-Gene Prognostic Assay
  • Active Comparator: Adjuvant Chemotherapy
    Adjuvant Chemotherapy is a current standard of care for intermediate or high-risk Stage I or Stage IIA non-squamous non-small cell lung cancer. Patients identified as intermediate or high-risk by the 14-Gene Prognostic Assay will be randomized either to this arm or the Observation Arm.
    Interventions:
    • Drug: Adjuvant Chemotherapy
    • Other: 14-Gene Prognostic Assay
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2020)
1050
Original Estimated Enrollment  ICMJE
 (submitted: March 22, 2013)
700
Estimated Study Completion Date  ICMJE May 15, 2025
Estimated Primary Completion Date May 15, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent
  • Age ≥ 18 years
  • Adequate tissue sample for the 14-Gene Prognostic Assay
  • Histologically documented completely resected (R0) Stage I or Stage IIA non-squamous NSCLC. Mixed histologies that include a squamous cell, 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 through 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 right- sided cancer and levels 2,4,5,6,7,8 9 for left-sided cancers.
  • Life expectancy excluding NSCLC diagnosis ≥ 5 years
  • ECOG performance status 0-1
  • Adequate haematological function:

    1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 AND
    2. Platelet count ≥ 100000 cells/mm3 AND
    3. Haemoglobin ≥ 9 g/dL (may be transfused to maintain or exceed this level)
  • Adequate liver function:

    1. Total bilirubin < 1.5 x upper limit of normal (ULN) AND
    2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
  • Adequate renal function, with Serum creatinine ≤ 1.5 x ULN
  • Completely healed incisions

Exclusion Criteria:

  • Final pathologic diagnosis of purse squamous cell histology, pure small cell or pure neuroendocrine histology, or any combination of only these three histologies.
  • Evidence of greater than stage II A pathologic staging
  • Evidence of incomplete resection
  • Pregnant or lactating women
  • Unwilling to use an effective means of contraception
  • Active infection, either systemic or at site of primary resection
  • Prior systemic chemotherapy or anti-cancer agent
  • Any pre- or post-operative radiotherapy
  • 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
  • Treatment with any investigational drug or participation in another clinical trial within 28 days prior to enrollment
  • Known hypersensitivity to any of the study treatment agents
  • Evidence of any other disease including infection that contraindicates the use of systemic cytotoxic chemotherapy or puts the patient at high risk for treatment related complications
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael Mann, MD 650-535-0030 mmann@encoreclinical.org
Contact: Carolyn Clary, RN 650-535-0030 cclary@encoreclinical.org
Listed Location Countries  ICMJE France,   Germany,   United States
Removed Location Countries China
 
Administrative Information
NCT Number  ICMJE NCT01817192
Other Study ID Numbers  ICMJE EC-120888
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Encore Clinical ( Razor Genomics )
Study Sponsor  ICMJE Razor Genomics
Collaborators  ICMJE Encore Clinical
Investigators  ICMJE
Principal Investigator: David R Spigel, MD Sarah Cannon, The Cancer Institute of HCA Healthcare
PRS Account Encore Clinical
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP