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

NCT05262985 | Unknown Phase 2 DMC

• 1 other identifier: ESR-20-20907
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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).

Conditions

Patients With Advanced Treatment Naive LCNEC

Outcome Measures

Primary Outcomes (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

  At 12 months

Secondary Outcomes (3)

• 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

Study Arms (1)

Treatment with Durvalumab+

OTHER

Comparison of standard treatment verses the addition of Durvalomab to the standard protocol.

Drug: Durvalumab

Interventions

Durvalumab DRUG

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

Treatment with Durvalumab+

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Carcinomatous meningitis or history of carcinomatous meningitis
• Prior treatment with an anti-PD-1/anti-PD-L1 agent/chemotherapy
• Patients who have received prior anti-PD-1/anti-PD-L1 agent/platinum-based chemotherapy as neo-adjuvant or adjuvant therapy with curative intent for non-metastatic disease must have experienced a disease-free interval of at least 6 months since the last anti-PD-1/anti-PD-L1 agent/chemotherapy administration.
• Patients who have received prior anti-PD-1/anti-PD-L1 agent:
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study
• Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy; patients with endocrine AE of ≤Grade 2 are permitted to enrol if they are stably maintained on appropriate replacement therapy and are asymptomatic
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consulting PI
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consulting PI
• Radiation therapy to the brain/lung within 1 week of study treatment
• Prior radiation to other sites (excluding brain and lung) may be completed at any point prior to study treatment
• Major surgery within 4 weeks of study treatment
• Any concurrent chemotherapy (other than per protocol), immune check-point inhibitors, biologic, or hormonal therapy for cancer treatment
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

Sponsors & Collaborators

• Elizabeth Dudnik: lead

Study Sites (1)

Assuta MC

Tel Aviv, 69710, Israel

RECRUITING

MeSH Terms

Interventions

durvalumab

Central Study Contacts

Osnat Albeck, MSC

CONTACT

972-3-7644016; osnatalb@assuta.co.il

Elizabeth Dudnik, MD

CONTACT

972-3-7644016; osnatalb@assuta.co.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Elizabeta Dudnik

Study Record Dates

• First Submitted: February 20, 2022
• First Posted: March 2, 2022
• Study Start: January 31, 2022
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2025
• Last Updated: March 2, 2022

Record last verified: 2022-02

Locations

IL (1)