Chemoradiotherapy With Surgery Followed by Consolidation Durvalumab

NCT06908070 | Recruiting Phase 4

• 1 other identifier: 2024-511711-21-00
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Lung cancer presents a significant treatment challenge, particularly in the heterogeneous stage III NSCLC patient population. While chemotherapy combined with high-dose radiotherapy (60 Gy in 30 fractions of 2 Gy once daily) is currently the recommended approach for unresectable stage III cases, it is associated with significant rates of locoregional and distant failures. Notably, the introduction of durvalumab consolidation therapy after chemoradiotherapy (CRT), as demonstrated in the PACIFIC study, has shown improved overall survival, primarily attributed to enhanced distant control. This improvement prompts further interest in investigating whether further improvements in locoregional control can lead to improved survival for patients. The present study aims to evaluate the feasibility of post-CRT surgery in patients with initially considered unresectable stage III (non-N3) NSCLC.

Conditions

Non-small Cell Lung Cancer Stage III

Keywords

Non-small cell lung cancer; NSCLC; Chemoradiotherapy; Surgery; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• The rates of severe surgical morbidity and mortality

  Grades 3-5 according to the Clavien-Dindo classifications for surgical complications

  Within 90-days of surgery

• Percentage of patients with high-grade treatment-related adverse events

  Grades 3-5 according to NCI CTCAE version 5.0

  Within 90-days of surgery

• Proportion of patients proceeding to durvalumab consolidation after surgery

  Number of patients starting durvalumab

  Within 2 months

Secondary Outcomes (2)

• R0 rate

  At surgery

• DFS at 2 years

  Two years after surgery

Study Arms (1)

Chemoradiotherapy plus surgery and immunotherapy

EXPERIMENTAL

Chemoradiotherapy followed by surgery and consolidation durvalumab

Drug: Consolidation durvalumab

Interventions

Consolidation durvalumab DRUG

Patients with initially unresectable stage III NSCLC will undergo surgery after chemoradiotherapy completion when the tumor is deemed resectable by the thoracic oncology tumor board and will then receive durvalumab

Also known as: Chemoradiotherapy, Surgery

Chemoradiotherapy plus surgery and immunotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed stage III (non-N3) NSCLC (TNM 8th edition), before start of concurrent chemoradiotherapy (CRT).
• In case of suspected N2-disease, mediastinal invasive staging (EUS, EBUS and/or mediastinoscopy) to prove N2 involvement before start of concurrent CRT is preferred.
• Initial MDT recommendation for a non-surgical treatment comprising concurrent CRT (platinum-doublet, 60 Gy in 30 fractions of 2 Gy once daily) followed by durvalumab
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years at time of study entry, i.e. the day of signing informed consent.
• Have a performance status of 0-1 on the ECOG Performance Scale at time of restaging.
• Body weight \>30 kg
• Demonstrate adequate normal organ and marrow function, as deemed acceptable by the treating physician in the context of CRT.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Must have a life expectancy of at least 12 weeks

You may not qualify if:

• Patients with TxN3 or M1 disease
• Patients with known actionable genomic alterations.
• The use of any CRT schemes other than those in ESMO recommendations (platinum doublet, 30 once-daily fractions of 2 Gy)
• Patients deemed inoperable based on cardiopulmonary function tests or comorbidity
• Unable to undergo CT-scan with iv-contrast
• Unable to remain supine for 15 min for the PET-low-dose CT scan
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• Participation in another clinical study with an investigational product during the last 4 weeks.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤4 weeks prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• History of allogenic organ transplantation.

Sponsors & Collaborators

• Idris Bahce: lead

Study Sites (1)

Amsterdam UMC, location VU Medical center

Amsterdam, Netherlands

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Chemoradiotherapy; Surgical Procedures, Operative

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)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Central Study Contacts

Chris Dickhoff, MD, PhD

CONTACT

0031 20 4444444; c.dickhoff@amsterdamumc.nl

Ilias Houda, MD

CONTACT

0031 20 444 3134; i.houda@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Pulmonologist

Study Record Dates

• First Submitted: March 27, 2025
• First Posted: April 3, 2025
• Study Start: December 17, 2024
• Primary Completion (Estimated): December 17, 2026
• Study Completion (Estimated): December 17, 2028
• Last Updated: April 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After publication
• Access Criteria: Deidentified data can be made available upon request

Locations

NL (1)