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

Lung Neoplasms Clinical Trial

— PACIFIC BRAZIL  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04230408
• Other study ID #: LACOG 2218
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 5, 2021
• Est. completion date: December 19, 2024

Study information

• Verified date: October 2023
• Source: Latin American Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: December 19, 2024
• Est. primary completion date: September 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• Durvalumab
Intensified chemo-immuno-radiotherapy with durvalumab in combination with carboplatin, paclitaxel and radiation

Locations

Country	Name	City	State
Brazil	Liga Norte Riograndense Contra o Câncer	Natal	Rio Grande Do Norte
Brazil	CPO	Porto Alegre	Rio Grande Do Sul
Brazil	COI Américas	Rio De Janeiro
Brazil	INCA	Rio De Janeiro	RJ
Brazil	Beneficiencia Portuguesa de São Paulo/Hospital São José	São Paulo
Brazil	ICESP	São Paulo

Sponsors (3)

Lead Sponsor	Collaborator
Latin American Cooperative Oncology Group	AstraZeneca, Libbs Farmacêutica LTDA

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.