Intensified Chemo-immuno-radiotherapy With Durvalumab for Stage III Non-Small Cell Lung Cancers

NCT04230408 | Completed Phase 2

• 1 other identifier: LACOG 2218
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 6

Brief Summary

This is a phase II study that will assess if Durvalumab (MEDI4736) used as induction chemo-immunotherapy followed by concurrent chemo-immuno-radiotherapy and consolidation immunotherapy may improve oncologic outcomes compared with standard of care chemoradiation followed by durvalumab (as in the PACIFIC trial) with a reasonable safety profile.

Conditions

Lung Neoplasms

Keywords

Stage III Non-Small Cell Lung Cancer; Unresectable Non-Small Cell Lung Cancer; Durvalumab; MEDI4736

Outcome Measures

Primary Outcomes (1)

• 12 months Progression-Free Survival

  Proportion of patients who are alive and progression-free 12 months after cycle 1, day 1 of induction treatment, estimated by the Kaplan-Maier method and using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  Tumor scans will be performed at baseline, after the induction and concomitant phases and 3, 6, 9, and 12 months after the last dose of radiation therapy.

Secondary Outcomes (3)

• Overall Survival (OS)

  OS will be evaluated until month 24 after C1D1.

• Overall response rate to induction treatment

  Tumor scans will be performed at baseline, after the induction and concomitant phases and 3, 6, 9, and 12 months after the last dose of radiation therapy.

• Patterns of Failure

  Tumor scans will be performed at baseline, after the induction and concomitant phases and 3, 6, 9, and 12 months after the last dose of radiation therapy.

Study Arms (1)

DURVALUMAB (MEDI4736) + carboplatin-paclitaxel

EXPERIMENTAL

Induction chemo-immunotherapy phase: Two cycles of Paclitaxel 200 mg/m2, Carboplatin AUC 6 and Durvalumab 1500 mg intravenously every 21 days. Concurrent chemo-immuno-radiotherapy phase: Radiation therapy concomitantly with: paclitaxel 50 mg/m2 intravenously every 7 days (+/- 3 days) until completion of radiation therapy, carboplatin AUC 2 intravenously every 7 days (+/- 3 days) until completion of radiation therapy and durvalumab 1500 mg intravenously every 21 days (+/- 6 days) for a maximum of 2 doses. Concurrent chemo-immuno-radiotherapy: Durvalumab 1500 mg intravenously every 28 days (+/- 7 days) for a maximum of 12 doses

Drug: Durvalumab

Interventions

Durvalumab DRUG

Intensified chemo-immuno-radiotherapy with durvalumab in combination with carboplatin, paclitaxel and radiation

Also known as: Carboplatin, Paclitaxel

DURVALUMAB (MEDI4736) + carboplatin-paclitaxel

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 non-small cell lung cancer.
• Stage III according to the American Joint Committee on Cancer (AJCC) Staging Manual, 8th edition.
• No prior systemic therapy, radiation therapy, or surgery for the current cancer.
• Age ≥ 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Body weight \>30kg
• Pre- or post-bronchodilator forced expiratory volume 1 ≥ 1.2 litres/second or ≥ 50% of predicted value
• Adequate normal organ and marrow function

You may not qualify if:

• Patients whose radiation treatment is likely to encompass a volume of whole lung receiving ≥ 20 Gy in total of more than 35% of lung volume.
• Patients whose radiation treatment is likely to deliver a cardiac dose V50 \> 25%
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
• Participation in another clinical study with an investigational product with anti-neoplastic activity during the last 3 weeks prior to treatment initiation
• 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
• History of allogenic organ transplantation.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
• Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
• Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 antibodies
• Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product.
• Prior radiation therapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of the investigational product.
• Active or prior documented autoimmune or inflammatory disorders
• Uncontrolled intercurrent illness
• History of another primary malignancy

Sponsors & Collaborators

• Latin American Cooperative Oncology Group: lead
• AstraZeneca: collaborator
• Libbs Farmacêutica LTDA: collaborator

Study Sites (6)

INCA

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Liga Norte Riograndense Contra o Câncer

Natal, Rio Grande do Norte, 59075-740, Brazil

Location

CPO

Porto Alegre, Rio Grande do Sul, Brazil

Location

COI Américas

Rio de Janeiro, Brazil

Location

Beneficiencia Portuguesa de São Paulo/Hospital São José

São Paulo, Brazil

Location

ICESP

São Paulo, Brazil

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Design

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

Model Details: Prospective single-arm study

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 18, 2020
• Study Start: March 5, 2021
• Primary Completion: October 7, 2024
• Study Completion: December 20, 2024
• Last Updated: February 11, 2025

Record last verified: 2025-02

Locations

BR (6)