Using ctDNA to Determine Therapies for Lung Cancer

NCT04966663 | Recruiting Phase 2 DMC

• 1 other identifier: ctDNA Lung RCT
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to look at whether the presence of circulating tumour DNA (ctDNA) in the blood can help to predict whether giving adjuvant treatment after surgery can decrease the chance of the cancer coming back in people with lung cancer.

Conditions

Non Small Cell Lung Cancer; Complete Surgical Resection; Circulating Tumor DNA

Outcome Measures

Primary Outcomes (1)

• Relapse Free Survival

  To demonstrate the impact of intensified adjuvant therapy on relapse-free survival (RFS) in patients at high risk of relapse post-resection identified by pre- or post-operative detectable ctDNA plasma levels in patients with resected T1-T4 (T3-4 multifocal only) N0M0 NSCLC.

  2 years

Secondary Outcomes (3)

• Rate of ctDNA clearance

  12 weeks

• Overall survival

  3 years

• Number of adverse events

  3 years

Study Arms (2)

Adjuvant chemo-immunotherapy therapy

EXPERIMENTAL

All participants will have blood taken for ctDNA testing. A cycle is 21 days. Pemetrexed (for participants with non-squamous non-small cell lung cancer), intravenously (by vein) on Day 1 of Cycles 1-4, OR gemcitabine (for all other participants) on Days 1 and 8 of Cycles 1-4. Cisplatin\*, intravenously (by vein) on Day 1 of Cycles 1-4 Nivolumab, intravenously (by vein) on Day 1 of Cycles 1-4 \*If cisplatin is not tolerated, carboplatin may be given instead

Drug: Nivolumab; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Procedure: ctDNA blood test

Observation

OTHER

All participants will have blood taken for ctDNA testing. Participants will be followed as per standard of care every 3 months.

Procedure: ctDNA blood test

Interventions

Nivolumab DRUG

Antineoplastic agent

Also known as: Opdivo, ONO-4538, BMS-936558, MDX1106

Adjuvant chemo-immunotherapy therapy

Pemetrexed DRUG

Antineoplastic agent

Also known as: Alimta, Pemfexy

Adjuvant chemo-immunotherapy therapy

Gemcitabine DRUG

Antineoplastic agent

Also known as: Gemzar, 2', 2'-difluoro 2'deoxycytidine, dFdC

Adjuvant chemo-immunotherapy therapy

Cisplatin DRUG

Antineoplastic agent

Also known as: Cisplatinum, platamin, neoplatin, cismaplat, cis-diamminedichloroplatinum(II) (CDDP), Platinol, Platinol-AQ

Adjuvant chemo-immunotherapy therapy

Carboplatin DRUG

Antineoplastic agent

Also known as: Paraplatin, Paraplatin-AQ, CBDCA, JM8, NSC 241240, Paraplatin NovaPlus

Adjuvant chemo-immunotherapy therapy

ctDNA blood test PROCEDURE

Blood will be collected for ctDNA testing

Adjuvant chemo-immunotherapy therapy; Observation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of screening
• Written informed consent obtained from the subject prior to performing any protocol-related procedures
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Weight ≥ 35 kg
• Must have a life expectancy of at least 24 months
• Complete surgical resection of T1-2N0M0 NSCLC or T3/T4 multifocal NSCLC
• Any pathologic subtype of NSCLC is eligible, including adenocarcinoma and squamous carcinoma. Patients with targetable genomic alterations without approved or available targeted adjuvant therapy options are eligible
• Patients with detectable plasma ctDNA before or after complete surgical resection are eligible (RaDaR TM assay, Inivata Morrisville, North Carolina, USA).
• No prior chemotherapy or radiotherapy is allowed for the current diagnosis of resected NSCLC.
• Adequate organ and marrow function as defined in Table 4 (3.1.1)
• Females of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception from screening to 180 days after the final dose of study treatment. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period
• Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from screening to 180 days after receipt of the final dose of study treatment. It is strongly recommended for the female partner of a male subject to also use a highly effective method of contraception throughout this period. In addition, male subjects must refrain from sperm donation while on study and for 180 days after the final dose of study treatment.

You may not qualify if:

• Participants that should receive adjuvant chemotherapy per standard of care (resected N1 or N2 disease, primary tumour \>=4 cm).
• Receipt of any conventional or investigational anticancer therapy within 21 days or radiotherapy within 14 days prior to the scheduled first dose of study treatment;
• Prior receipt of any immune-mediated anti-cancer therapy including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1 antibodies including nivolumab and agents targeting CD73, CD39, or adenosine receptors;
• Incomplete surgical resection;
• Concurrent enrolment in another therapeutic clinical study of systemic anti-cancer treatment. Enrolment in observational or supportive studies will be allowed;
• Subjects with a recent history of myocardial infarction, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment;
• Active autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment. The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia.
• Subjects with hypothyroidism (e.g., following Hashimoto syndrome) not requiring systemic treatment or stable on hormone replacement.
• Subjects with psoriasis not requiring systemic treatment.
• Any chronic skin condition that does not require systemic therapy.
• Subjects with celiac disease controlled by diet alone;
• Have known uncontrolled human immunodeficiency virus (HIV)-1/2 infection.
• Participants with HIV (known HIV 1/2 antibodies positive) are allowed if all of the following conditions are met: CD4+ T-cell counts ≥350 cells/uL; no opportunistic infection within the past 12 months; on established anti-retroviral therapy for at least 4 weeks; and an HIV viral load less than 400 copies/mL.
• History of primary immunodeficiency, solid organ transplantation, or active tuberculosis (by clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice). In settings where there is clinical or radiographic evidence of tuberculosis, active disease must be excluded prior to enrolment. Subjects who have had adequately treated tuberculosis may be enrolled upon discussion with the coordinating Principal Investigator.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Pemetrexed; Gemcitabine; Cisplatin; Carboplatin

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Natasha Leighl

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natasha Leighl, M.D.

CONTACT

416-946-4645; Natasha.Leighl@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 19, 2021
• Study Start: March 28, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

CA (1)