Lung Neoplasms
Conditions
Keywords
Stage III Non-Small Cell Lung Cancer, Unresectable Non-Small Cell Lung Cancer, Durvalumab, MEDI4736
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.
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.
Interventions
DRUGDurvalumab
Intensified chemo-immuno-radiotherapy with durvalumab in combination with carboplatin, paclitaxel and radiation
Sponsors
AstraZeneca
Libbs Farmacêutica LTDA
Latin American Cooperative Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective single-arm study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12 months Progression-Free Survival | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | OS will be evaluated until month 24 after C1D1. | Time from cycle 1, day 1 of induction treatment until death due to any cause. |
| 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. | The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) using RECIST v1.1. |
| 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. | Rate of disease failure in local, regional and distant sites |
Countries
Brazil
Outcome results
None listed