Model to Predict pCR and IrAEs in Early Stage Non-small Cell Lung Cancer

NCT06250829 | Recruiting FDA Drug

• 1 other identifier: Pre-PLaN
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Lung cancer is the chief cause of cancer death. The new standard-of-care (SOC) in operable lung cancer combines chemotherapy and an immune-stimulating drug before the surgery (neoadjuvant approach). This results in a large increase in complete cancer clearance rates compared to chemotherapy alone (±30% with combination vs ±4% with chemotherapy alone), leading to much better long-term survival and probably many more cures. However, most still don't achieve complete clearance, and a few have increases in, or spread of, their tumors while on treatment. Therefore, we need to understand why some patients benefit (responders) and others don't benefit (non-responders) on an immunotherapy-based treatment. Also, some patients unpredictably develop severe immune-type side effects related to the immunotherapy drug, although such side effects may be associated with improved anti-cancer effects. In short, the same treatment can result in complete cancer clearance in one patient, and in a worst-case scenario may result in severe toxicity or fail to control spread/growth thus precluding surgery. The immune system obviously plays a key role in both benefit and harm, yet most of the research in this field has focused only on the cancer. We plan an in-depth study in 60 patients, focusing on the cancer as well as the patient's immune system, pre-surgery. This will enable us to identify factors predicting complete cancer clearance, and the occurrence of immune-type side effects. Using highly sophisticated resources available to us here in London, we will develop predictive models enabling better patient management (including possible avoidance of surgery), and identification of key biological differences between major responders and non-responders, to highlight important new targets for the development of even newer and better therapies.

Conditions

Non-small Cell Lung Cancer Stage IB (Resectable); Non-small Cell Lung Cancer Stage II (Resectable); Non-small Cell Lung Cancer Stage ⅢA (Resectable)

Outcome Measures

Primary Outcomes (3)

• Predictive power of various parameters to predict pCR and IrAE's

  18 months

• To determine the predictive power (sensitivity, specificity, receiver operator characteristic (ROC) curves) of a model, combining predictive variables, in predicting pCR.

  18 months

• To determine whether a similar model can be constructed to predict irAEs.

  18 months

Interventions

Observational OTHER

Observational study of body composition, cytokine profile, immune status, ctDNA, serial radiology.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Stage iB to IIIA resectable non-small cell lung cancer

You may qualify if:

• \. Participants with histologically confirmed Stage IB (≥ 4 cm), II, IIIA (N2) NSCLC (as per the 8th American Joint Committee on Cancer (AJCC)) who are considered to have resectable disease.
• \. Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
• \. Participants must have tumor tissue available for PD-L1 immunohistochemical (IHC) testing.
• \. Eastern Cooperative Group (ECOG) Performance Status 0-2. 5. Able to give informed consent.

You may not qualify if:

• \. Presence of locally advanced, unresectable, or metastatic disease. 2. Participants with known EGFR mutations, ALK or ROS1 translocation. 3. Subjects with active, known, or suspected autoimmune disease (except subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment).
• \. Subjects with a condition requiring systemic treatment with either corticosteroids (10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• \. Subjects with previous malignancies are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study (non-melanoma skin cancer and other indolent malignancies not requiring any treatment and that are unlikely to affect blood-based biomarkers are allowed).

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Biopsy specimens housed in pathology department and whole blood and plasma repositories; fecal specimens

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Central Study Contacts

Saurav Verma, MD

CONTACT

519 685 8500; saurav.verma@lhsc.on.ca

Mark D Vincent, MD

CONTACT

519 685 8500; mark.vincent@lhsc.on.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start: October 12, 2023
• Primary Completion: October 30, 2024
• Study Completion: May 30, 2025
• Last Updated: February 9, 2024

Record last verified: 2024-02

Locations

CA (1)