Surgery After Verifying Existing Disease in Locally Advanced Operable Lung Cancer: A Pilot Study

NCT ID: NCT06743555

Last Updated: 2024-12-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-28
• Study Completion Date: 2032-02-29

Brief Summary

The SAVED LUNG study is a pilot Phase I trial evaluating safety and feasibility of observation versus standard-of-care surgery in operable Stage II-III (excluding N3) NSCLC patients (PD-L1 ≥50%) who achieve complete clinical response following neoadjuvant platinum-doublet chemotherapy and immunotherapy. Participants are randomized to observation or surgery after rigorous restaging, with primary endpoints focusing on safety and feasibility. Secondary objectives include rates of cross-over to surgery, event-free survival, and overall survival, while exploratory endpoints examine ctDNA clearance and its association with clinical response.

Detailed Description

After neoadjuvant therapy, all participants undergo intensified re-staging invasive and non-invasive modalities to assess for complete clinical response:

• Chest CT;
• PET/CT scan;
• Bronchoscopy;
• EBUS;
• EUS;
• Re-biopsy of lesions that were deemed to be positive for cancer; this includes re-biopsies of all positive lymph nodes and transthoracic needle aspiration of tumors.

Participants with complete clinical response defined by absence of disease as measured by all the above modalities will be randomized 1:1 to either observation or surgery.

Only patients with complete clinical response will proceed to the randomization stage of the trial. Block randomization will occur 1:1 with two participants per block. All other patients will remain on study and undergo therapy as per standard-of-care and will have follow-up on study. Both groups will have blood collected for ctDNA at this stage. For participants in the surgery arm, the blood sample will be 3 weeks after surgery, while participants in surveillance only arm will have the blood sample 3 weeks after randomization.

Conditions

Non-Small Cell Lung Cancer; Immunotherapy; Neoadjuvant Therapy; Thoracic Surgery; Complete Response

Keywords

NSCLC; Neoadjuvant immunotherapy; Complete response; Surveillance; PD-L1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard-of-care surgery

Participants undergo surgery followed by the same surveillance schedule as Arm A. ctDNA testing is conducted 3 weeks post-surgery and again at 6 months. Surveillance includes low-dose CT scans, physical examinations, and ECOG assessments every 3 months for 12 months, with long-term monitoring at regular intervals up to 5 years.

Group Type: ACTIVE_COMPARATOR

Standard-of-care surgery

Intervention Type: PROCEDURE

Patients randomized to this arm will undergo standard-of-care thoracic surgery and undergo post-operative surveillance with serial radiological follow-up and ctDNA monitoring

Observation without surgery

Participants undergo surveillance without surgery, including a low-dose CT scan of the thorax and upper abdomen, ECOG assessment, and physical examination every 3 months for the first 12 months. Additional ctDNA testing is performed 3 weeks post-randomization and at 6 months. Long-term follow-up includes similar assessments every 6-12 months up to 5 years.

Group Type: EXPERIMENTAL

Observation without surgery

Intervention Type: OTHER

Patients randomized to this arm will forego standard-of-care thoracic surgery and will undergo strict surveillance based on serial radiological follow-up and ctDNA monitoring

Interventions

Observation without surgery

Patients randomized to this arm will forego standard-of-care thoracic surgery and will undergo strict surveillance based on serial radiological follow-up and ctDNA monitoring

Intervention Type: OTHER

Standard-of-care surgery

Patients randomized to this arm will undergo standard-of-care thoracic surgery and undergo post-operative surveillance with serial radiological follow-up and ctDNA monitoring

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• > 18 years of age
• The participant has provided documented informed consent for the trial.
• Histologically confirmed (by core biopsy) NSCLC and confirmed clinical stages II-III (excluding N2) NSCLC (AJCC 8th edition) amenable to receive neoadjuvant chemo-immunotherapy defined by: nivolumab 3mg/kg Q3W in combination with platinum doublet chemotherapy (cisplatin or carboplatin with paclitaxel or pemetrexed Q3W) for 3 cycles.
• PD-L1 tumor proportion score >50%
• Has no history of immunodeficiency, HBV, HCV, HIV.
• For female participants:

1. Has no active pregnancy (Refer to "Female participants").

2. For a woman of child-bearing potential (WOCBP), use of a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least 180 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.

3. A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within either 24 hours (urine) or 72 hours (serum) before the first dose of study intervention.

4. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Has adequate hematological, renal and hepatic function per Investigator discretion required for platinum-doublet chemotherapy plus immunotherapy.
• Has signed the written consent.

Exclusion Criteria

• Has one of the following tumor locations/types:

1. NSCLC involving the superior sulcus

2. Large cell neuro-endocrine cancer (LCNEC)

3. Sarcomatoid tumor

• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has had an allogenic tissue/solid organ transplant.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
• Has a known additional malignancy that is progressing or requires active treatment within the past (5 years). Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, bladder carcinoma, or carcinoma in situ (eg, in situ cervical cancer or breast carcinoma) that have undergone potentially curative therapy are not excluded.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antoine Desilets, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier de l'Université de Montréal (CHUM)

Locations

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Countries

Canada

Central Contacts

Antoine Desilets, MD, MSc

Role: CONTACT

Phone: 514-890-8444

Email: antoine.desilets.med@ssss.gouv.qc.ca

Wiam Belkaid, PhD

Role: CONTACT

Phone: 514-836-3273

Email: wiam.belkaid.chum@ssss.gouv.qc.ca

Facility Contacts

Antoine Desilets, MD, MSc

Role: primary

Wiam Belkaid, PhD

Role: backup

References

Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16.

Reference Type: RESULT

PMID: 29658848 (View on PubMed)

Other Identifiers

2025-12255

Identifier Type: -

Identifier Source: org_study_id