Neoadjuvant Immunotherapy With Durvalumab (MEDI4736) in Non-Surgical Early Stage or Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Followed by Radical Radiotherapy or Chemoradiotherapy

NCT05267392 | Unknown Phase 1

• 2 other identifiers: ESR-18-138282019-002884-90
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study proposes to evaluate the safety and efficacy of an anti-PD-L1 (durvalumab) agent as neoadjuvant therapy in patients diagnosed with localized NSCLC who are planned to undergo radical RT or CRT. The hypothesis to be tested for the primary objective is that the treatment of durvalumab followed by RT/CRT will be safe and well tolerated in subjects with NSCLC.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer (NSCLC); PD1/PD-L1; anti-PD1/PD-L1 blockade; Non-Surgical Early Stage or Locally Advanced NSCLC

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose-Limiting Toxicity (DLT)

  Rate of patients without Dose-Limiting Toxicity (DLT) evaluated from durvalumab administration until 5 - 6 weeks after the last session of RT/CRT.

  Through study development up to 5 - 6 weeks after the last session of RT/CRT for each enrolled patient

Secondary Outcomes (4)

• Safety of durvalumab followed by RT/CRT

  Through study development up to 17 weeks for each enrolled patient

• objective response rate

  Through study development up to 17 weeks for each enrolled patient

• Pathologic response rate

  Through study development up to 17 weeks for each enrolled patient

• feasibility of durvalumab followed by RT/CRT

  Through study development up to 3 years

Study Arms (1)

Durvalumab

EXPERIMENTAL

All subjects enrolled in the study will receive open-label neoadjuvant durvalumab 1500 mg followed by standard of care RT/RCT

Drug: Durvalumab; Other: standard of care RT/RCT

Interventions

Durvalumab DRUG

Patients will receive 1500 mg of durvalumab (MEDI4736) via IV infusion

Durvalumab

standard of care RT/RCT OTHER

standard of care RT/RCT

Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Age ≥ 18 years at time of screening.
• ECOG performance status of 0 or 1.
• Life expectancy of at least 12 weeks.
• Body weight \>30 kg.
• Histologically documented NSCLC.
• Measurable disease, as defined by RECIST.
• Adequate normal organ and marrow function defined by the following laboratory results obtained within 14 days prior to durvalumab administration:
• Hemoglobin ≥ 9.0 g/dL.
• White blood cell (WBC) counts \> 2.5 x 109/L.
• Absolut neutrophil count (ANC) ≥ 1.5 x 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to durvalumab treatment).
• Lymphocyte count ≥ 0.5 x 109/L.
• Platelet count ≥100 x 109/L.
• AST, ALT, and alkaline phosphatase ≤ 2.5 x the institutional upper limit of normal (ULN).
• Serum bilirubin ≤ 1.5 x ULN. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks prior to durvalumab administration.
• 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.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Prior chemotherapy or radiation therapy for lung cancer.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 5 years.
• Patients with celiac disease controlled by diet alone.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

Sponsors & Collaborators

• Instituto Portugues de Oncologia, Francisco Gentil, Porto: lead
• AstraZeneca: collaborator

Study Sites (1)

Instituto Português de Oncologia do Porto FG, EPE (IPO-Porto)

Porto, 4200-072, Portugal

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Júlio Oliveira, MD

CONTACT

+351225084000; earlytrials@ipoporto.min-saude.pt

Joana H Maia

CONTACT

+351225084000; clinicalstudies@ipoporto.min-saude.pt

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: March 4, 2022
• Study Start: February 16, 2021
• Primary Completion: July 1, 2023
• Study Completion: January 1, 2024
• Last Updated: March 4, 2022

Record last verified: 2021-12

Locations

PT (1)