Durvalumab (MEDI4736) Plus Platinum-based Chemotherapy in Advanced LCNEC: a Pilot Phase II Study

Sponsor
Elizabeth Dudnik
Study ID
NCT05262985
Phase
PHASE2
Status
Unknown

Conditions

  • Patients With Advanced Treatment Naive LCNEC

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    In patients with advanced treatment naive LCNEC, treatment with Durvalumab+ Cisplatin/Carboplatin+Etoposide

Study Details

PROTOCOL SYNOPSIS Clinical Protocol ESR-20-20907 Study Title: Durvalumab (MEDI4736) plus platinum-based chemotherapy in advanced large-cell neuroendocrine tumors of lung (LCNEC): a pilot phase II study Protocol Number: ESR-20-20907 Clinical Phase: phase II Study Duration: 30 months Investigational Product(s) and Reference Therapy: Investigational Product: Durvalumab (MEDI4736) Durvalumab concentrate for solution for infusion will be supplied in glass vials containing 500 mg durvalumab at a concentration of 50 mg/mL Reference Therapy: Cisplatin/Carboplatin+Etoposide Research Hypothesis Primary hypothesis: 1.1 In patients with advanced treatment naive LCNEC, treatment with Durvalumab+ Cisplatin/Carboplatin+Etoposide is associated with 12-month PFS rate of at least 18%. Secondary hypothesis: 1.2 In patients with advanced treatment naïve LCNEC, treatment with Durvalumab+ Cisplatin/Carboplatin+Etoposide is associated with ORR of 50%. 1.3 In patients with advanced treatment naïve LCNEC, treatment with Durvalumab+ Cisplatin/Carboplatin+Etoposide is associated with 12-months OS rate of at least 50%. 1.4 Incidence of grade ≥3 adverse events is less than 60%. Exploratory hypothesis: 1.5 There is a positive correlation between the small-cell lung cancer-like molecular subtype and efficacy parameters (ORR, PFS, OS), and also between high TMB and efficacy parameters (ORR, PFS, OS) of treatment with Durvalumab+Cisplatin/Carboplatin+Etoposide in patients with advanced treatment naive LCNEC. Objectives Primary Objective: 1.1 To assess progression-free survival (PFS at 12 months, RECIST v. 1.1) with Durvalumab+ Cisplatin/Carboplatin+Etoposide in patients with advanced treatment-naive LCNEC. Secondary Objectives: 1.2 To assess objective response rate (ORR at best response) according to Response Evaluation Criteria in Solid Tumors, v. 1.1 (RECIST v. 1.1) with Durvalumab+ Cisplatin/Carboplatin+Etoposide in patients with advanced treatment naive LCNEC. 1.3 To assess overall survival (OS at 12 months) with Durvalumab+ Cisplatin/Carboplatin+Etoposide in patients with advanced treatment-naive LCNEC. 1.4 To further evaluate the safety profile of Durvalumab+Cisplatin/Carboplatin+Etoposide in patients with advanced treatment naive LCNEC (CTCAE v. 5.0). Exploratory Objectives: 1.5 To assess the predictive effect of tumor molecular subtype (small-cell lung cancer - like versus non-small cell lung cancer - like, assessed by NGS), tumor mutational burden (TMB, mut/Mb assessed by NGS) and PD-L1 (assessed by TPS - by IHC using 22C3 antibody) on ORR, PFS, and OS with Durvalumab+Cisplatin/Carboplatin+Etoposide in patients with advanced treatment-naive LCNEC. Study Design: * Open-label non-randomized non-comparative single-center pilot phase 2 study * Response assessment: brain/chest/abdominal/pelvic CT scan every 8 weeks+-7 days * PFS, ORR - assessed by the board-certified radiology expert experienced in RECIST v. 1.1 evaluation; OS assessment Number of Centers: single center Number of Patients: 22 Study Population: Adult patients (aged ≥18 years) with histologically or cytologically documented advanced LCNEC (stage IV or stage III not eligible for definitive treatment) without prior systemic treatment for advanced disease. Investigational Product(s), Dose and Mode of Administration: The enrolled patients will receive IV durvalumab 1500 mg (administered on day 1 of each 21-day cycle), IV etoposide 100 mg/m² (administered on days 1-3 of each 21-day cycle), with investigator's choice of either IV carboplatin area under the curve 5 mg/mL per min or IV cisplatin 80 mg/m² (administered on day 1 of each 21-day cycle) for four cycles followed by maintenance IV durvalumab 1500 mg (administered on day 1 of each 28-day cycle).

Key Dates

Start date
Jan 31, 2022
Status verified
Feb 2022
Primary completion
Jan 1, 2024
Completion
Jan 1, 2025

Study Design

Enrollment
22 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Other: Treatment with Durvalumab+
    Comparison of standard treatment verses the addition of Durvalomab to the standard protocol.

Primary Outcome Measure

To assess progression-free survival (PFS at 12 months, RECIST v. 1.1) with Durvalumab+ Cisplatin/Carboplatin+Etoposide in patients with advanced treatment-naive LCNEC [ Time Frame: At 12 months ]

Central Contacts