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Non Small Cell Lung CancerPhase 2ctDNA Lung RCTNCT04966663

Using ctDNA to Determine Therapies for Lung Cancer

A Phase 2 study testing Nivolumab, Pemetrexed and Gemcitabine in people with Non Small Cell Lung Cancer and Complete Surgical Resection, run by University Health Network, Toronto at 1 site in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab, Pemetrexed and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteCanada
Study dates
28 Mar 2022to 1 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 43Show fewer
  • 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.
  • 4.1.2 Exclusion Criteria
  • 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.
  • Other invasive malignancy within 2 years. Non-invasive malignancies (i.e., cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast that has been surgically cured) are permitted.
  • Known allergy or hypersensitivity to investigational product formulations.
  • History of more than one event of infusion related reactions (IRR) requiring permanent discontinuation of IV drug treatment.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring antibiotic therapy, uncontrolled hypertension, bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the subject to give written informed consent.
  • Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment. The following are exceptions to this criterion:
  • Intranasal, topical, inhaled corticosteroids or local steroid injections (e.g., intra articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent.
  • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication).
  • Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment (Note: Subjects, if enrolled, should not receive live vaccine during the study and 180 days after the last dose of study treatment). Vaccination with an inactivated vaccine is permitted at any time.
  • Major surgery (as defined by the investigator) within 28 days prior to the scheduled first dose of study treatment or still recovering from prior surgery. Local procedures (e.g., placement of a systemic port, core needle biopsy, etc) are allowed without needing to wait for the 28-day recovery period.
  • Females who are pregnant, lactating, or intend to become pregnant during their participation in the study.
  • Subjects who are involuntarily incarcerated or are unable to willingly provide consent or are unable to comply with the protocol procedures.
  • Any condition that, in the opinion of the investigator, would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results
  • Any condition that, in the opinion of the investigator, would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Nivolumab or other agents used in the study.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Natasha Leighl, M.D. contact

416-946-4645

Natasha.Leighl@uhn.ca

Canada1 site, 1 recruiting

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

    Natasha Leighl, M.D.

    Recruiting

Other trials in Canada

About this study

Official title: From Liquid Biopsy to Cure: Using ctDNA Detection of Minimal Residual Disease to Identify Patients for Curative Therapy After Lung Cancer Resection

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.

Read the detailed description

For people who have early stage non-small cell lung cancer (NSCLC), the usual treatment is surgery. For many people, surgery is enough to get rid of all the cancer. However, for some people, there may be a little bit of cancer remaining. If there is some cancer left over, it may lead to the cancer regrowing. This is called relapse.

Many cancers shed little bits of their DNA (deoxyribonucleic acid, molecules that contain instructions for how cells develop and function) into the bloodstream. A blood test can be used to test for the amount of circulating tumour DNA (ctDNA). Some studies have shown that the presence of ctDNA in the blood may predict cancer recurrence.

The purpose of this research study is to see if adjuvant treatment (additional treatment given after primary treatment) can help decrease the risk of the cancer recurring in people with lung cancer who have ctDNA detected in their blood after surgery.

Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo, ONO-4538, BMS-936558, MDX1106

    Antineoplastic agent

  • PemetrexedDrug

    Also called Alimta, Pemfexy

    Antineoplastic agent

  • GemcitabineDrug

    Also called Gemzar, 2', 2'-difluoro 2'deoxycytidine, dFdC

    Antineoplastic agent

  • CisplatinDrug

    Also called Cisplatinum, platamin, neoplatin, cismaplat

    Antineoplastic agent

  • CarboplatinDrug

    Also called Paraplatin, Paraplatin-AQ, CBDCA, JM8

    Antineoplastic agent

  • ctDNA blood testProcedure or surgery

    Blood will be collected for ctDNA testing

Study groups in NCT04966663
Study groupRoleWhat they receive
Adjuvant chemo-immunotherapy therapyExperimentalAll 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
Receives: Drug: Nivolumab; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Procedure: ctDNA blood test
ObservationOtherAll participants will have blood taken for ctDNA testing. Participants will be followed as per standard of care every 3 months.
Receives: Procedure: ctDNA blood test

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years

Secondary outcomes (3)

  1. Rate of ctDNA clearance

    To estimate and compare the ctDNA detection rates at 12 weeks post-randomization in those receiving adjuvant chemo-immunotherapy versus observation.

    Measured: 12 weeks

  2. Overall survival

    To compare overall survival (OS) of patients receiving adjuvant chemo-immunotherapy versus observation.

    Measured: 3 years

  3. Number of adverse events

    To determine safety and tolerability of adjuvant chemo-immunotherapy with the combination of nivolumab with cisplatin and pemetrexed or nivolumab with cisplatin and gemcitabine.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2021
  2. Study start28 Mar 2022
  3. Primary completion1 Aug 2026 (estimated)
  4. Study completion1 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04966663
Sponsor's protocol ID
ctDNA Lung RCT
Acronym
ctDNA Lung RCT
Status last verified
Dec 2025
First submitted
8 Jul 2021
Last updated
18 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Pemetrexed and Gemcitabine in people with Non Small Cell Lung Cancer and Complete Surgical Resection, run by University Health Network, Toronto at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 43 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Natasha Leighl, M.D. (416-946-4645, Natasha.Leighl@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapse Free Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04966663.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.

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