Predictive Assay for Decision Making in Adjuvant Therapy (PADMA)

Predictive Assay for Decision Making in Adjuvant Therapy (PADMA)

Prospective Registrational Trial to Define Real World Outcomes of Patients with Completely Resected Stage I or IIA (tumor < or = 5cm, node negative) Non-squamous Non-Small Lung Cancer (NSCLC) Identified as High, Intermediate, or Low Risk by a 14-Gene Prognostic Assay DetermaRx being Considered for Adjuvant Platinum-based chemotherapy or other adjuvant therapy versus Observation

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Adjuvant; Other: Observation

Detailed Description

This is a prospective, non-randomized, 2 arm, multi-center study in patients with histologically documented non-squamous NSCLC who have undergone complete resection (R0) of the primary tumor with pathologically stage I or IIA disease. Routine paraffin-embedded tumor specimens from completely resected (R0) stage I or IIA patients with non-squamous NSCLC will undergo testing with the DetermaRx 14-Gene Prognostic Assay and will be designated as HIGH, INTERMEDIATE or LOW risk by the assay. The physician and patient will determine the best treatment course and will be assigned to treatment arm based on decision of adjuvant therapy or observation:

1. Adjuvant treatment with a standard NSCLC platin-based doublet, 4 cycle (21-day) regimen of the investigator's choice (Arm 1) or other adjuvant therapy (Arm 1a) which can include combination of chemotherapy and targeted therapy, immunotherapy or other.
2. Observation (Arm 2) All patients will be observed for progression free survival and overall survival to the end of study or death, whichever occurs first.

All patients will be observed for disease free survival and overall survival to the end of study or death, whichever occurs first

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20037
      • George Washington Medical Faculty Associates
  • Florida
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Cancer Center
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Our Lady of the Lake Regional Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
  • Texas
    • San Antonio, Texas, United States, 78240
      • Texas Oncology-San Antonio Medical Center
    • San Antonio, Texas, United States, 78249
      • Methodist Healthcare
    • Wichita Falls, Texas, United States, 76310
      • Texas Oncology-Wichita Falls Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
    • Fredericksburg, Virginia, United States, 22401
      • Mary Washington Hospital
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center Everett
    • Vancouver, Washington, United States, 98683
      • Peace Health
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Medicine
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with non-squamous NSCLC who have undergone complete resection (R0) of the primary tumor and who have been documented to have pathologically confirmed stage I or IIA disease

Description

Inclusion Criteria:

1. Written informed consent using the appropriate approved Institutional Review Board (IRB) approved 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 (18 months from randomization).
4. Adequate tissue sample, paraffin block with tumor occupying at least 25% of the tissue surface area, for the 14 -gene prognostic assay, DetermaRx
5. Histologically documented completely resected (R0) Stage I or IIA non-squamous NSCLC per 8th edition, TNM staging system. Mixed histology cases (adenosquamous), large cell, or adenocarcinoma not otherwise classified (NOS) 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 lobectomy, bilobectomy, segmentectomy, sleeve lobectomy and pneumonectomy. Resections via segmentectomy or wedge resection should be limited to patients with a peripheral tumor 2 cm or less with wide margins (> 2 cm or > the size of the nodule). Complete resection must also be accompanied, at a minimum, by intra-operative systematic mediastinal lymph node sampling. Systematic sampling is defined as removal of at least one representative lymph node each from levels 4 and 7 for a right-sided cancer and from levels 5 and/or 6 and 7 for left-sided cancers. Complete mediastinal lymph node dissection (MLND), however, is preferred, and is defined as resection of all lymph nodes at those same levels for right- and left-sided cancers.
6. ECOG performance status 0-1
7. No prior anti-neoplastic (NSCLC ) treatment in the pre-operative or post-operative setting (including chemotherapy, targeted therapy, immunotherapy, radiation, ablative procedures, etc.)

Exclusion Criteria:

1. Final pathologic diagnosis of pure squamous cell, pure small cell, or pure neuroendocrine histology, or any combination of only these three histological subtypes.
2. Evidence of greater than stage IIA pathologic staging
3. Evidence of incomplete resection (R1)
4. Prior systemic chemotherapy or anti-cancer agent for NSCLC
5. Any pre- or post-operative radiotherapy for the index tumor being considered for enrollment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment Arm; Treatment Arm 1: 4 cycles of adjuvant treatment with a standard NSCLC cisplatin-based doublet regimen or carboplatin-based regimen of physician choice. Treatment 1A: other adjuvant therapy or combination of adjuvant therapies (targeted therapy, immunotherapy, or other)	Drug: Adjuvant; Adjuvant treatment with a standard NSCLC platin-based doublet, 4 cycle (21-day) regimen of the investigator's choice (Arm 1) or other adjuvant therapy (Arm 1a) which can include combination of chemotherapy and targeted therapy, immunotherapy or other.; Other: Observation; All patients will be observed for progression free survival and overall survival to the end of study or death, whichever occurs first.
Observation only; All patients will be observed for progression free survival and overall survival to the end of study or death, whichever occurs first.	Other: Observation; All patients will be observed for progression free survival and overall survival to the end of study or death, whichever occurs first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free Survival (DFS)	To compare Disease Free Survival (DFS) in patients with resected, stage I or IIA non-squamous NSCLC found to be at HIGH/INTERMEDIATE Risk by DetermaRX choosing to undergo adjuvant therapy using a platinum-based doublet or other adjuvant therapy versus observation.	30-36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Objectives	To evaluate use patterns of DetermaRx in guiding use of adjuvant platinum-based chemotherapy across early-stage resected lung cancer; To evaluate DFS in DetermaRx LOW risk patients who are put on observation alone; To evaluate whether use of DetermaRx HIGH/INTERMEDIATE vs. LOW to guide adjuvant platinum-based therapy results in improved OS in patients; To evaluate if EGFR mutational status impacts use of adjuvant platinum-based therapy in DetermaRx HIGH/INTERMEDIATE vs. LOW patients	30-36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Analyses	To evaluate predictive value of DetermaRx in driver positive NSCLC patients receiving chemotherapy, targeted therapy or both.; To evaluate predictive value of DetermaRx early NSCLC patients receiving chemotherapy + immunotherapy or other combination adjuvant therapies; To evaluate predictive value of other histological features on pathology in association with DetermaRx as well as additional biomarkers (i.e., KRAS, TP53, STK11, PD-L1 expression, etc.) if performed by physician in combination with DetermaRx results and related outcomes	30-36 months

Collaborators and Investigators

• Sponsor: OncoCyte
• Collaborators: ClinLogix. LLC
• Investigators: Principal Investigator: Corey Langer, MD

Publications and helpful links

General Publications

• Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, Goldman JW, Laktionov K, Kim SW, Kato T, Vu HV, Lu S, Lee KY, Akewanlop C, Yu CJ, de Marinis F, Bonanno L, Domine M, Shepherd FA, Zeng L, Hodge R, Atasoy A, Rukazenkov Y, Herbst RS; ADAURA Investigators. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Oct 29;383(18):1711-1723. doi: 10.1056/NEJMoa2027071. Epub 2020 Sep 19.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2022
• Primary Completion (Actual): October 28, 2022
• Study Completion (Actual): October 28, 2022

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Non-squamous Non-Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: PADMA Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Not determined yet

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No