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

Overview

The optimal treatment for stage I non-small cell lung cancer (NSCLC) remains controversial. Radiographic surveillance alone has been recommended for stage I 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 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 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 NSCLC patients at high risk of death within five years after operation. A new prognostic tool, the Pervenio™ Lung RS Assay, which has been validated and definitively demonstrated in large scale studies to identify high-risk stage I 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.

Full Title of Study: “A Randomized Prospective Trial of Adjuvant Chemotherapy in Patients With Completely Resected Stage I Non-Squamous Non-Small Cell Lung Cancer Identified as High Risk by the Pervenio™ Lung RS Assay”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2021

Interventions

  • Drug: Adjuvant Chemotherapy
  • Other: Radiographic surveillance
    • Serial radiographic surveillance is a current standard of care for stage I lung cancer
  • Other: Pervenio™ Lung RS 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 early stage 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 high-risk will be randomized to either adjuvant chemotherapy or observation.

Arms, Groups and Cohorts

  • Active Comparator: Observation
    • Post-operative observation of stage I non-small cell lunger cancer with Radiographic Surveillance is a current standard of care. Patients identified as high-risk by the Pervenio™ Lung RS Assay will be randomized either to this arm or the Adjuvant Chemotherapy Arm.
  • Active Comparator: Adjuvant Chemotherapy
    • Adjuvant Chemotherapy is a current standard of care for high-risk stage I non-small cell lung cancer. Patients identified as high-risk by the Pervenio™ Lung RS Assay will be randomized either to this arm or the Observation Arm.

Clinical Trial Outcome Measures

Primary Measures

  • Overall Survival
    • Time Frame: 2 years

Secondary Measures

  • Disease-Free Survival
    • Time Frame: 2 years

Participating in This Clinical Trial

Inclusion Criteria

  • Written informed consent
  • Age ≥ 18 years
  • Adequate tissue sample for Pervenio™ testing
  • Histologically documented completely resected (R0) Stage I non-squamous NSCLC
  • 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 squamous cell histology
  • Evidence of greater than stage I 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Encore Clinical
  • Collaborator
    • Life Technologies Corporation
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Thierry Jahan, MD, Principal Investigator, University of California, San Francisco

References

Kratz JR, He J, Van Den Eeden SK, Zhu ZH, Gao W, Pham PT, Mulvihill MS, Ziaei F, Zhang H, Su B, Zhi X, Quesenberry CP, Habel LA, Deng Q, Wang Z, Zhou J, Li H, Huang MC, Yeh CC, Segal MR, Ray MR, Jones KD, Raz DJ, Xu Z, Jahan TM, Berryman D, He B, Mann MJ, Jablons DM. A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies. Lancet. 2012 Mar 3;379(9818):823-32. doi: 10.1016/S0140-6736(11)61941-7. Epub 2012 Jan 27.

Kratz JR, Van den Eeden SK, He J, Jablons DM, Mann MJ. A prognostic assay to identify patients at high risk of mortality despite small, node-negative lung tumors. JAMA. 2012 Oct 24;308(16):1629-31. doi: 10.1001/jama.2012.13551.

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