Patients With Advanced Treatment Naive LCNEC
Conditions
Brief summary
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).
Interventions
DRUGDurvalumab
In patients with advanced treatment naive LCNEC, treatment with Durvalumab+ Cisplatin/Carboplatin+Etoposide
Sponsors
Elizabeth Dudnik
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced- stage (stage IV or stage III not eligible for definitive treatment) LCNEC without prior systemic treatment for advanced disease * Measurable disease by RECIST 1.1 criteria (at least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline) * ECOG PS≤1 * Body weight \>30kg * Life expectancy of at least 3 months * Brain metastases are allowed providing these are asymptomatic or clinically stable after surgery or radiation therapy (either stereotactic radiotherapy or whole brain radiotherapy), and not requiring corticosteroid therapy \- 10 mg prednisone or equivalent are allowed * Normal hematologic, renal, liver and thyroid function parameters: * Absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL; * Creatinine clearance ≥ 40 mL/min (≥ 50 mL/min if cisplatin-based regimen will be chosen); * Total bilirubin ≤ 1.5 mg/dL; ALT+ AST levels £ 2.5 × ULN; for patients with liver metastases £ 5 × ULN; * TSH within normal limits, if TSH is abnormal - normal total T3/free T3 and free T4 * Female patients with reproductive potential (postmenopausal: ≥ 12 months of non-therapy-induced amenorrhea or surgically sterile) must have a negative pregnancy test (serum/urine) prior to starting treatment * All female patients with reproductive potential and male patients with partners of childbearing potential, must agree to use barrier contraception methods while receiving the study treatment and for 90 days after stopping the study treatment * Age ≥18 * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | At 12 months |
Secondary
| Measure | Time frame |
|---|---|
| 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. | At 12 months |
| To assess overall survival (OS at 12 months) with Durvalumab+ Cisplatin/Carboplatin+Etoposide in patients with advanced treatment-naive LCNEC. | At 12 months |
| To further evaluate the safety profile of Durvalumab+Cisplatin/Carboplatin+Etoposide in patients with advanced treatment naive LCNEC (CTCAE v. 5.0). | At 12 months |
Countries
Israel
Contacts
Primary ContactOsnat Albeck, MSC
Backup ContactElizabeth Dudnik, MD
Outcome results
None listed