Clinical trial NCT04230408: Intensified Chemo-immuno-radiotherapy With Durvalumab for Stage III Non-Small Cell Lung Cancers
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Neoplasms
Keywords: Stage III Non-Small Cell Lung Cancer
Unresectable Non-Small Cell Lung Cancer
Durvalumab
MEDI4736
Lead sponsor: Latin American Cooperative Oncology Group
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Libbs Farmacêutica LTDA
First posted: 2020-01-18
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective single-arm study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 12 months Progression-Free Survival
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: OS will be evaluated until month 24 after C1D1.
measure: Overall response rate to induction treatment
timeFrame: 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.
measure: Patterns of Failure
timeFrame: 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.
Other outcomes:
Locations:
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: CPO
state: Rio Grande Do Sul
city: Rio De Janeiro
country: Brazil
facility: INCA
state: RJ
city: Rio De Janeiro
country: Brazil
facility: COI Américas
city: São Paulo
country: Brazil
facility: Beneficiencia Portuguesa de São Paulo/Hospital São José
city: São Paulo
country: Brazil
facility: ICESP
Study officials:
References: