Intensified Chemo-immuno-radiotherapy With Durvalumab for Stage III Non-Small Cell Lung Cancers (PACIFIC BRAZIL)

Intensified Chemo-immuno-radiotherapy With Durvalumab (MEDI4736) for Stage III Non-Small Cell Lung Cancers (NSCLCs): a Brazilian Single Arm Phase II Study (PACIFIC BRAZIL)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Neoplasms
• Intervention / Treatment: Drug: Durvalumab

Detailed Description

Prospective, non-randomized, open label, single arm, multi-institutional, phase 2 study, including patients with stage III non-small cell lung cancer able to receive concurrent chemoradiation. Eligible patients will then receive treatment as follows:

Induction chemo-immunotherapy Two 21-day cycles of carboplatin, paclitaxel and durvalumab will be given BEFORE concurrent chemo-immuno-radiotherapy.

Thereafter, patients without progressive disease (or patients with disease progression that is still locally advanced and can be safely encompassed within tolerable radiation fields) will receive concurrent chemo-immuno-radiotherapy, as follows:

Concurrent chemo-immuno-radiotherapy Concurrent carboplatin, paclitaxel, and durvalumab with radiation therapy, initiated preferably 3-5 weeks after the last dose of induction chemo-immunotherapy.

Thereafter, patients without progressive disease will receive consolidation immunotherapy, as follows:

Consolidation immunotherapy Twelve 28-day cycles of durvalumab will be given, initiated preferably within one week following concurrent chemo-immuno-radiotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio De Janeiro, Brazil
    • COI Américas
  • São Paulo, Brazil
    • Beneficiencia Portuguesa de São Paulo/Hospital São José
  • São Paulo, Brazil
    • ICESP
  • RJ
    • Rio De Janeiro, RJ, Brazil
      • INCA
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59075-740
      • Liga Norte Riograndense Contra O Cancer
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • CPO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA

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

EXCLUSION CRITERIA

1. 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.
2. Patients whose radiation treatment is likely to deliver a cardiac dose V50 > 25%
3. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
4. Participation in another clinical study with an investigational product with anti-neoplastic activity during the last 3 weeks prior to treatment initiation
5. 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
6. History of allogenic organ transplantation.
7. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
8. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
9. Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
10. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 antibodies
11. Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product.
12. Prior radiation therapy to the region of the study cancer that would result in overlap of radiation therapy fields.
13. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of the investigational product.
14. Active or prior documented autoimmune or inflammatory disorders
15. Uncontrolled intercurrent illness
16. History of another primary malignancy
17. Known active infection including tuberculosis , hepatitis B, hepatitis C, or human immunodeficiency virus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: DURVALUMAB (MEDI4736) + carboplatin-paclitaxel; 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; Intensified chemo-immuno-radiotherapy with durvalumab in combination with carboplatin, paclitaxel and radiation; Other Names: Carboplatin; Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from cycle 1, day 1 of induction treatment until death due to any cause.	OS will be evaluated until month 24 after C1D1.
Overall response rate to induction treatment	The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) using 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.
Patterns of Failure	Rate of disease failure in local, regional and distant sites	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.

Collaborators and Investigators

• Sponsor: Latin American Cooperative Oncology Group
• Collaborators: AstraZeneca; Libbs Farmacêutica LTDA

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Estimated): September 2, 2024
• Study Completion (Estimated): December 19, 2024

Study Registration Dates

• First Submitted: January 10, 2020
• First Submitted That Met QC Criteria: January 14, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Durvalumab; Stage III Non-Small Cell Lung Cancer; Unresectable Non-Small Cell Lung Cancer; MEDI4736
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Carboplatin; Paclitaxel; Durvalumab
• Other Study ID Numbers: LACOG 2218

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No