Durvalumab With Carboplatin and Etoposide Chemotherapy in Pulmonary Large-cell Neuroendocrine Carcinoma (LCNEC)

NCT06418087 | Recruiting Phase 2

• 1 other identifier: DUPLE- GOIRC- 05-2020
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 15

Brief Summary

A prospective multicenter, single-arm phase II study enrolling treatment-naïve patients with metastatic pulmonary large-cell neuroendocrine carcinoma (LCNEC)

Conditions

Pulmonary Large-cell Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (1)

• Efficacy of the combination of carboplatin + etoposide + durvalumab in treatment-naïve patients, as first line treatment, with metastatic pulmonary LCNEC

  Efficacy of the combination of carboplatin + etoposide Overall Survival rate at 1 year

  1 year

Secondary Outcomes (2)

• Activity of the combination of carboplatin + etoposide + durvalumab as first-line treatment for patients with metastatic pulmonary LCNEC

  1 year

• Number of Participants with treatment-related Adverse Events as assessed by CTCAE v. 5.0 - The safety and tolerability profile of the combination of carboplatin + etoposide + durvalumab as first-line treatment for patients with metastatic pulmonary LCNEC

  1 year

Study Arms (1)

Patient with Pulmonary Large-cell Neuroendocrine Carcinoma

EXPERIMENTAL

All enrolled patients will receive intravenous infusion of durvalumab 1500 mg on day 1 (induction phase) with carboplatin (AUC 5 on day 1), etoposide (100 mg/sqm on days 1-3) every 3 weeks, and durvalumab (1500 mg on day 1) administered every three weeks for up to 4 cycles (induction phase) or until progression of disease, unacceptable toxicity, patient refusal or loss of clinical benefit (for durvalumab). Treatment with intravenous durvalumab (1500 mg on day 1) every 4 weeks ± 3 days (maintenance phase) will continue until completion of 24 courses (for a total of 28 courses, including the 4 courses of induction phase) or 2 years of treatment whichever occurs first, disease progression, unacceptable toxicity, patient refusal or loss of clinical benefit.

Drug: Durvalumab 50 MG/1 ML Intravenous Solution [IMFINZI]

Interventions

Durvalumab 50 MG/1 ML Intravenous Solution [IMFINZI] DRUG

Intravenous infusion of durvalumab 1500 mg on day 1 (induction phase) with carboplatin (AUC 5 on day 1), etoposide (100 mg/sqm on days 1-3) every 3 weeks, and durvalumab (1500 mg on day 1) administered every three weeks for up to 4 cycles (induction phase) or until progression of disease, unacceptable toxicity, patient refusal or loss of clinical benefit (for durvalumab). Treatment with intravenous durvalumab (1500 mg on day 1) every 4 weeks ± 3 days (maintenance phase) will continue until completion of 24 courses (for a total of 28 courses, including the 4 courses of induction phase) or 2 years of treatment whichever occurs first, disease progression, unacceptable toxicity, patient refusal or loss of clinical benefit.

Also known as: Carboplatino AHCL 10 mg/ml Concentrate for solution for infusion, Etoposide 20 mg/ml Concentrate for solution for infusion

Patient with Pulmonary Large-cell Neuroendocrine Carcinoma

Eligibility Criteria

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

You may qualify if:

• 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.
• Age ≥18 years at the time of study entry
• Histologically or cytologically (cell blocks only; smears are not acceptable) documented pulmonary large-cell neuroendocrine carcinoma (LCNEC)
• Stage IV disease or unresectable stage IIIB, which cannot be safely encompassed in a single RT field (e.g. supraclavicular N3, T4 by infiltration of vertebral body), according to the AJCC 8th edition Cancer Staging Manual
• Body weight \>30 kg

You may not qualify if:

• No need for concomitant chest irradiation
• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• At least one lesion measurable according to RECIST v 1.1 outside of the CNS, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements
• Adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1500/µL, hemoglobin ≥9 g/dL (5.58 mmol/L), and platelets ≥100,000/µL.
• Adequate hepatic and renal functions:
• Total bilirubin \< 1.5 times the upper limits of normal \[ULN\]
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Serum creatinine ≤1.5 times the ULN or creatinine clearance, calculated according to the formula of Cockcroft and Gault \> 60 ml/min
• The patient has adequate coagulation function as defined by International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) \< 1.5 x ULN.). Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤3.0.
• Female patients must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
• Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form of contraception that results in a low failure rate (\< 1% per year) when used consistently and correctly, and to continue its use for 6 months after the last dose of chemotherapy or 90 days after the last dose of durvalumab, whichever occurs last. Such methods include: combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, and vasectomized partner (on the understanding that this is the only one partner during the whole study duration).

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead

Study Sites (15)

IRCCS AOU Policlinico Sant'Orsola Malpighi

Bologna, BO, 40138, Italy

RECRUITING

Istituto Oncologico del Mediterraneo IOM - Viagrande Catania

Viagrande, CT, 95029, Italy

NOT YET RECRUITING

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l. IRCCS

Meldola, FC, 47014, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, FI, 50134, Italy

NOT YET RECRUITING

Humanitas Research Hospital

Rozzano, MI, 20089, Italy

NOT YET RECRUITING

Istituto Oncologico Veneto IRCCS-IOV

Padua, PD, 35128, Italy

NOT YET RECRUITING

Centro di riferimento oncologico di Aviano

Aviano, PN, 33081, Italy

NOT YET RECRUITING

Azienda Ospedaliera San Camillo Forlanini-Ospedale San Camillo

Roma, RM, 00152, Italy

NOT YET RECRUITING

AOU Sassari - Ospedale SS. Annunziata

Sassari, SS, 07100, Italy

NOT YET RECRUITING

AOU Ospedale San Luigi Gonzaga

Orbassano, TO, 10043, Italy

RECRUITING

Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari

Bari, 70120, Italy

NOT YET RECRUITING

Azienda Usl Toscana nord ovest Ospedale San Luca

Lucca, 55100, Italy

NOT YET RECRUITING

Ospedale San Gerardo Monza

Monza, 20900, Italy

RECRUITING

A.O.R.N. "A. Cardarelli"

Napoli, 80131, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria di Parma

Parma, 43126, Italy

NOT YET RECRUITING

MeSH Terms

Interventions

durvalumab; Solutions; Etoposide

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Andrea Ardizzoni

  Gruppo Oncologico Italiano di Ricerca Clinica

  STUDY DIRECTOR

Central Study Contacts

Davide Campana

CONTACT

+390512142204; goirc-duple@goirc.org

Michele Tognetto

CONTACT

+390512142204; goirc-duple@goirc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: May 16, 2024
• Study Start: May 27, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 16, 2024

Record last verified: 2024-05

Locations

IT (15)