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Pulmonary Large-cell Neuroendocrine CarcinomaPhase 2DUPLENCT06418087

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

A Phase 2 study testing Durvalumab 50 MG/1 ML Intravenous Solution [IMFINZI] in people with Pulmonary Large-cell Neuroendocrine Carcinoma, run by Gruppo Oncologico Italiano di Ricerca Clinica at 15 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab 50 MG/1 ML Intravenous Solution [IMFINZI]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
15 sitesItaly
Study dates
27 May 2022to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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

Who cannot join

  • 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
Show all 45Show fewer
  • 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

Trial locations and contacts

15 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Davide Campana contact

+390512142204

goirc-duple@goirc.org

Michele Tognetto contact

+390512142204

goirc-duple@goirc.org

15 sites in 1 country

Italy15 sites, 15 recruiting

  • Centro di riferimento oncologico di Aviano

    Aviano, PN, 33081

    Alessandro Del Conte, alessandro.delconte@cro.it

    Not yet recruiting

  • Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari

    Bari, 70120

    Mauro Cives, mauro.cives@uniba.it

    Not yet recruiting

  • IRCCS AOU Policlinico Sant'Orsola Malpighi

    Bologna, BO, 40138

    Davide Campana, +390512143067, davide.campana@unibo.it

    Recruiting

  • Azienda Ospedaliera Universitaria Careggi

    Florence, FI, 50134

    Lorenzo Antonuzzo, antonuzzol@aou-careggi.toscana.it

    Not yet recruiting

  • Azienda Usl Toscana nord ovest Ospedale San Luca

    Lucca, 55100

    Editta Baldini, editta.baldini@uslnordovest.toscana.it

    Not yet recruiting

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

    Meldola, FC, 47014

    Angelo Delmonte, angelo.delmonte@irst.emr.it

    Not yet recruiting

  • Ospedale San Gerardo Monza

    Monza, 20900

    Diego Cortinovis, d.cortinovis@asst-monza.it

    Recruiting

  • A.O.R.N. "A. Cardarelli"

    Naples, 80131

    Ferdinando Riccardi, nando.riccardi@gmail.com

    Not yet recruiting

  • AOU Ospedale San Luigi Gonzaga

    Orbassano, TO, 10043

    Paolo Bironzo, paolo.bironzo@unito.it

    Recruiting

  • Istituto Oncologico Veneto IRCCS-IOV

    Padova, PD, 35128

    Giulia Pasello, giulia.pasello@iov.veneto.it

    Not yet recruiting

  • Azienda Ospedaliera Universitaria di Parma

    Parma, 43126

    Paola Bordi, pbordi@ao.pr.it

    Not yet recruiting

  • Azienda Ospedaliera San Camillo Forlanini-Ospedale San Camillo

    Roma, RM, 00152

    Rita Migliorino, MMigliorino@scamilloforlanini.rm.it

    Not yet recruiting

  • Humanitas Research Hospital

    Rozzano, MI, 20089

    Luca Toschi, luca.toschi@cancercenter.humanitas.it

    Not yet recruiting

  • AOU Sassari - Ospedale SS. Annunziata

    Sassari, SS, 07100

    Antonio Pazzola, antonio.pazzola@aousassari.it

    Not yet recruiting

  • Istituto Oncologico del Mediterraneo IOM - Viagrande Catania

    Viagrande, CT, 95029

    Dario Giuffrida, giuffridadario@alice.it

    Not yet recruiting

Other trials in Italy

About this study

Official title: A Multicenter Phase II, Single Arm Study of Durvalumab (MEDI 4736) With Carboplatin Plus Etoposide for 4 Cycles Followed by Durvalumab Maintenance in Patients With Metastatic Pulmonary Large-cell Neuroendocrine Carcinoma (LCNEC)

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

Read the 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.

Being tested
Durvalumab 50 MG/1 ML Intravenous Solution [IMFINZI]

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called Carboplatino AHCL 10 mg/ml Concentrate for solution for infusion, Etoposide 20 mg/ml Concentrate for solution for infusion

    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.

Study groups in NCT06418087
Study groupRoleWhat they receive
Patient with Pulmonary Large-cell Neuroendocrine CarcinomaExperimentalAll 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.
Receives: Drug: Durvalumab 50 MG/1 ML Intravenous Solution [IMFINZI]

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 1 year

Secondary outcomes (2)

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

    Activity of the combination of carboplatin + etoposide + durvalumab as first-line treatment for patients with metastatic pulmonary LCNEC Median OS PFS ORR DCR and DoR at 1 year

    Measured: 1 year

  2. 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

    Safety and tolerability profile of the combination of carboplatin + etoposide + durvalumab as first-line treatment for patients with metastatic pulmonary LCNEC

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2024
  2. Study start27 May 2022
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06418087
Sponsor's protocol ID
DUPLE- GOIRC- 05-2020
Acronym
DUPLE
Status last verified
May 2024
First submitted
11 Aug 2022
Last updated
16 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab 50 MG/1 ML Intravenous Solution [IMFINZI] in people with Pulmonary Large-cell Neuroendocrine Carcinoma, run by Gruppo Oncologico Italiano di Ricerca Clinica at 15 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Davide Campana (+390512142204, goirc-duple@goirc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of the combination of carboplatin + etoposide + durvalumab in treatment-naïve patients, as first line treatment, with metastatic pulmonary LCNEC (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06418087.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.

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