Trial Title:
Durvalumab With Carboplatin and Etoposide Chemotherapy in Pulmonary Large-cell Neuroendocrine Carcinoma (LCNEC)
NCT ID:
NCT06418087
Condition:
Pulmonary Large-cell Neuroendocrine Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Neuroendocrine
Etoposide
Durvalumab
Pharmaceutical Solutions
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Durvalumab 50 MG/1 ML Intravenous Solution [IMFINZI]
Description:
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.
Arm group label:
Patient with Pulmonary Large-cell Neuroendocrine Carcinoma
Other name:
Carboplatino AHCL 10 mg/ml Concentrate for solution for infusion
Other name:
Etoposide 20 mg/ml Concentrate for solution for infusion
Summary:
A prospective multicenter, single-arm phase II study enrolling treatment-naïve patients
with metastatic pulmonary large-cell neuroendocrine carcinoma (LCNEC)
Detailed description:
This is a prospective multicenter, single-arm phase II study enrolling treatment-naïve
patients with metastatic pulmonary large-cell neuroendocrine carcinoma (LCNEC). Enrolled
subjects will receive a combination of intravenous carboplatin (AUC 5 on day 1),
etoposide (100 mg/sqm on days 1-3), and durvalumab (1500 mg on day 1) administered every
three weeks for a total of 4 courses (induction phase) or until progression of disease,
unacceptable toxicity, patient refusal or loss of clinical benefit. Treatment with
intravenous durvalumab (1500 mg on day 1) every 4 weeks (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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- No prior chemotherapy or treatment with another systemic anti-cancer agent. Patients
who have received prior chemoradiotherapy for locally advanced pulmonary LCNEC must
have been treated with curative intent and experienced a treatment-free interval of
at least 6 months from last chemotherapy, radiotherapy or chemoradiotherapy cycle to
disease relapse, progression, or diagnosis of metastatic LCNEC. In this case, all
toxicity from previous treatments should be resolved and no cumulative toxicity of
grade >1 should be present (see also Section 4.2 "Exclusion criteria").
- 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).
- Male patients who are sexually active must be willing to use barrier contraceptives
(i.e., by use of condoms) during sex with all partners during treatment with
chemotherapy and for at least 6 months after the final dose of chemotherapy or 90
days after the last dose of durvalumab, whichever occurs last, to avoid exposing the
embryo. Men must refrain from donating sperm during this same period
- Ability to comply with the study protocol, in the investigator's judgment
Exclusion Criteria:
- Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is
required within 4 weeks prior to randomization) requiring immediate radiotherapy for
palliation. Patients with asymptomatic CNS lesions are eligible, provided that all
of the following criteria are met:
- The patient has no history of intracranial hemorrhage, spinal cord hemorrhage or
hemorrhagic intracranial lesions
- At least 14 days between the end of stereotactic radiotherapy or whole brain
radiotherapy and initiation of study treatment, or at least 28 days between
neurosurgical resection and initiation of study treatment
- The patient is on a dose of corticosteroids ≤ 10 mg of oral prednisone or
equivalent; anticonvulsant therapy at a stable dose is permitted
- Metastases are limited to the cerebellum or the supratentorial region (i.e., no
metastases to the midbrain, pons, medulla or spinal cord)
- There is no evidence of interim progression between completion of CNS directed
therapy (if administered) and initiation of study treatment
- History of leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures
- Patients with indwelling catheters (e.g., Pleura-Cath) are allowed.
- Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >
12 mg/dL or corrected calcium > ULN)
- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C
- Patients with a past or resolved HBV infection (defined as the presence of hepatitis
B core antibody [anti-HBc] and absence of HBsAg) are eligible.
- Patients positive for hepatitis C (HCV) antibody are eligible if polymerase chain
reaction is negative for HCV RNA.
- Significant traumatic injury or radiotherapy involving an extensive field within the
last 4 weeks prior to first dose of study treatment or anticipation of the need for
major surgery during study treatment. Palliative radiotherapy to a limited field is
allowed if concluded at least 2 weeks prior enrolment.
- Other malignancies (previous or current), except for adequately treated in situ
carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin,
localized prostate cancer surgically treated with curative intent or ductal
carcinoma in situ treated surgically treated with curative intent or if previous
malignancy was more than 5 years prior and there are no signs or symptoms of
recurrence
- Major surgery (including open biopsy) within 28 days prior to first dose of protocol
therapy, or minor surgery/subcutaneous venous access device placement within 7 days
prior to the first dose of protocol therapy. The patient has elective or planned
major surgery to be performed during the course of the clinical trial.
- Prior allogeneic stem cell or solid organ transplantation.
- Patients with any underlying medical condition that might be aggravated by treatment
or which cannot be controlled i.e. patients with active serious infection,
uncontrolled diabetes mellitus, pericardial effusion.
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment
other than those in the present study. Concurrent use of hormonal therapy for
non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Treatment with any other investigational agent within 30 days prior to starting
study treatment, or 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
- Evidence of any other disease, metabolic dysfunction, physical examination finding
or laboratory finding giving reasonable suspicion of a disease or condition that
contra-indicates the use of an investigational drug or puts the patient at high risk
for treatment-related complications
- 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 may be included but only after
consultation with the study physician
- Patients with celiac disease controlled by diet alone
- History or active autoimmune neurologic paraneoplastic syndrome (e.g. non-infectious
encephalitis, Lambert-Eaton syndrome etc.) or any other immune-mediated
paraneoplastic syndrome.
- Patients with SIADH or ectopic ATCH production are allowed on trial
- Patient has received a live-virus vaccination within 30 days of planned treatment
start. Seasonal flu vaccines that do not contain live virus are permitted. Note:
Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to
30 days after the last dose of IP.
- History of idiopathic pulmonary fibrosis, including pneumonitis, drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan. History of radiation pneumonitis in the radiation field
(fibrosis) is permitted
- Prior therapy with any anti-PD-1, anti-PD-L1including durvalumab, or anti-PD-L2
agent and anti-CTL-A4 agent.
- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives
(whichever is longer) prior to initiation of study treatment.
- Any condition requiring systemic treatment with either corticosteroids or other
immunosuppressive medications within 14 days of randomization. The following are
exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone
or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- History or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating Investigator.
- History of allergies or hypersensitivity to any study drugs or study drug components
or CHO derived products.
- The patient is pregnant or breast-feeding
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria
- 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 carboplatin, etoposide or durvalumab may be included only after
consultation with the Study Physician.
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 6 months after last chemotherapy dose or 90 days after the last dose of
durvalumab, whichever occurs last. Patients should refrain from donating sperm from
the start of dosing until 4 months after discontinuing study treatment.
- Patients should not donate blood whilst on this study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
IRCCS AOU Policlinico Sant'Orsola Malpighi
Address:
City:
Bologna
Zip:
40138
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Davide Campana
Phone:
+390512143067
Email:
davide.campana@unibo.it
Facility:
Name:
Istituto Oncologico del Mediterraneo IOM - Viagrande Catania
Address:
City:
Viagrande
Zip:
95029
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Dario Giuffrida
Email:
giuffridadario@alice.it
Facility:
Name:
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l. IRCCS
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Angelo Delmonte
Email:
angelo.delmonte@irst.emr.it
Facility:
Name:
Azienda Ospedaliera Universitaria Careggi
Address:
City:
Firenze
Zip:
50134
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Lorenzo Antonuzzo
Email:
antonuzzol@aou-careggi.toscana.it
Facility:
Name:
Humanitas Research Hospital
Address:
City:
Rozzano
Zip:
20089
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Luca Toschi
Email:
luca.toschi@cancercenter.humanitas.it
Facility:
Name:
Istituto Oncologico Veneto IRCCS-IOV
Address:
City:
Padova
Zip:
35128
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Giulia Pasello
Email:
giulia.pasello@iov.veneto.it
Facility:
Name:
Centro di riferimento oncologico di Aviano
Address:
City:
Aviano
Zip:
33081
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Alessandro Del Conte
Email:
alessandro.delconte@cro.it
Facility:
Name:
Azienda Ospedaliera San Camillo Forlanini-Ospedale San Camillo
Address:
City:
Roma
Zip:
00152
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Rita Migliorino
Email:
MMigliorino@scamilloforlanini.rm.it
Facility:
Name:
AOU Sassari - Ospedale SS. Annunziata
Address:
City:
Sassari
Zip:
07100
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Antonio Pazzola
Email:
antonio.pazzola@aousassari.it
Facility:
Name:
AOU Ospedale San Luigi Gonzaga
Address:
City:
Orbassano
Zip:
10043
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Paolo Bironzo
Email:
paolo.bironzo@unito.it
Facility:
Name:
Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari
Address:
City:
Bari
Zip:
70120
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Mauro Cives
Email:
mauro.cives@uniba.it
Facility:
Name:
Azienda Usl Toscana nord ovest Ospedale San Luca
Address:
City:
Lucca
Zip:
55100
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Editta Baldini
Email:
editta.baldini@uslnordovest.toscana.it
Facility:
Name:
Ospedale San Gerardo Monza
Address:
City:
Monza
Zip:
20900
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Diego Cortinovis
Email:
d.cortinovis@asst-monza.it
Facility:
Name:
A.O.R.N. "A. Cardarelli"
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Ferdinando Riccardi
Email:
nando.riccardi@gmail.com
Facility:
Name:
Azienda Ospedaliera Universitaria di Parma
Address:
City:
Parma
Zip:
43126
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Paola Bordi
Email:
pbordi@ao.pr.it
Start date:
May 27, 2022
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Gruppo Oncologico Italiano di Ricerca Clinica
Agency class:
Other
Source:
Gruppo Oncologico Italiano di Ricerca Clinica
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06418087
