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Neuroendocrine CarcinomaPhase 2SENECANCT03387592

CAPTEM or FOLFIRI as SEcond-line Therapy in NEuroendocrine CArcinomas

A Phase 2 study testing CPT-11, Calcio levofolinate and 5-Fluorouracil in people with Neuroendocrine Carcinoma, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 23 sites in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a randomized phase II non comparative study. Patients with metastatic Neuroendocrine Carcinomas (NEC) Grade 3, will be enrolled in the study and will be randomly assigned to receive FOLFIRI or CAPTEM as second line treatment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Carcinoma
What is being tested?
CPT-11, Calcio levofolinate and 5-Fluorouracil
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
23 sitesItaly
Study dates
6 Mar 2017to 28 Feb 2022
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Histopathologic diagnosis of neuroendocrine carcinomas (GEP NEC and lung NEC), G3 with ki67 > 20%. Other rare sites of origin such as genitourinary or gynecological or larynx or unknown origin neuroendocrine carcinoma with Ki67 > 20% will be included.
  • Male or Female, aged >=18 years.
  • Measurable disease according to RECIST 1.1 criteria.
  • Patients who already received a first line treatment for metastatic disease with platinum compound-based regimen chemotherapy (Cisplatin/Carboplatin and Etoposide, folfox4 or Capecitabine-Oxaliplatin).
  • Previous treatments with immuno checkpoint-inhibitor and/or everolimus are permitted
  • Life expectancy greater than 3 months
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  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Adequate haematological, liver and renal function:
  • neutrophils > 2.0 x 109 /L, platelet > 100 x 109 /L, hemoglobin > 10g/dL, total bilirubin < 1 Upper Normal Limit (UNL), Aspartate aminotransferase (ASAT) and Alanine transaminase (ALAT) < 2.5 x UNL or < 5 x UNL in presence of liver metastases, alkaline phosphatase < 2.5 x UNL; patients with ASAT or ALAT >1.5 x UNL associated with alkaline phosphatase >2.5 x UNL are not eligible.); creatinine <1.5 UNL. In presence of borderline values, the calculated creatinine clearance according to Cockcroft-Gault formula, 60 ML/min.
  • If female of childbearing potential highly effective birth control methods, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials", (2014_09_15 section 4.1) are mandatory. Highly effective birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug. Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after final study drug administration. Two acceptable methods of birth control thus include Condom (barrier method of contraception) and one of the following is required ( established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), for more than 6 months.
  • Written informed consent signed and dated before registration procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirement.
  • Brain metastases allowed if asymptomatic at study baseline. Whole brain irradiation or focal treatment for Central Nervous System (CNS) metastases are permitted.

Who cannot join

  • Ki67 index ≤ 20 %.
  • Patients with metastatic NECs already treated with irinotecan regimen.
  • Patients with a known hypersensitivity to fluorouracil or calcium levofolinate or Irinotecan or their recipients.
  • All acute toxic effects of any prior therapy (including surgery radiation therapy, chemotherapy) must have resolved to a grade <= 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE).
  • Life expectancy minor than 3 months.
  • ECOG performance status >2.
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  • Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
  • severely impaired lung function (spirometry and diffusing capacity of lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or Oxygen saturation that is 88% or less at rest, in room air).
  • uncontrolled diabetes as defined by fasting serum glucose >1.5 x UNL.
  • any active (acute or chronic) or uncontrolled infections/disorders
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition.
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients with uncontrolled or symptomatic brain metastases will be excluded because they often develop progressive neurologic dysfunction that can be confounding of neurologic and other adverse events
  • Other malignancy with a disease-free interval of less than 5 years (except non melanoma skin cancer or low grade superficial bladder cancer).

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

Italy23 sites

  • Az. Osp. Ospedali Riuniti di Ancona

    Ancona, AN, 60020

  • Centro di Riferimento Oncologico di Aviano

    Aviano, Pordenone, 33081

  • A.O.U. Policlinico di Bari

    Bari, BA, 70124

  • IRCCS IST. Tumori Bari - Giovanni Paolo II

    Bari, BA, 70124

  • Policlinico S. Orsola-Malpighi

    Bologna, 40138

  • Ospedale di Bolzano

    Bolzano

  • ASST Spedali Civili di Brescia

    Brescia, BS, 25123

  • IRCCS "Saverio De Bellis"

    Castellana Grotte

  • Ospedale Civile degli Infermi

    Faenza, RA

  • Ospedale di Feltre

    Feltre, Belluno, 32032

  • AOU Careggi

    Florence, FI, 50134

  • Ospedale "Vito Fazzi"

    Lecce

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

    Meldola, FC, 47014

  • Istituto Europeo di Oncologia

    Milan, MI

  • Istituto Nazionale Tumori Milano

    Milan, MI

  • Azienda Ospedaliera-Universitaria di Modena

    Modena, MO

  • AOU San Luigi Gonzaga

    Orbassano, TO, 10043

  • Istituto Oncologico Veneto

    Padova

  • Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

    Palermo, PA, 90127

  • Azienda Ospedaliera-Universitaria di Parma

    Parma

  • Ospedale S.Chiara - AOU Pisana

    Pisa

  • Policlinico Campus Biomedico Roma

    Roma, RM, 00128

  • Azienda Ospedaliere Universitaria Integrata Verona

    Verona, VR, 37134

Other trials in Italy

About this study

Official title: A Randomized Phase II Trial of Capecitabine and Temozolomide (CAPTEM) or FOLFIRI as SEcond-line Therapy in NEuroendocrine CArcinomas and Exploratory Analysis of Predictive Role of Positron Emission Tomography (PET) Imaging and Biological Markers

This is a randomized phase II non comparative study. Patients with metastatic Neuroendocrine Carcinomas (NEC) Grade 3, will be enrolled in the study and will be randomly assigned to receive FOLFIRI or CAPTEM as second line treatment. Disease control rate (DCR) and safety are primary objectives, secondary objectives are Disease control rate (OS), Progression Free Survival (PFS), quality of life and toxicity of subsequent line of therapy (after Progression Disease PD) with an observational purpose.

Read the detailed description

This is a multicenter randomized phase II non comparative study. Patients with metastatic NEC G3, will be enrolled in the study and will be randomly assigned to receive FOLFIRI or CAPTEM as second line treatment The primary objective is to assess DCR and the safety as co-primary objective. The secondary objectives are: OS, PFS, quality of life and toxicity of subsequent line of therapy (after Progression Disease PD) with an observational purpose.

The secondary exploratory objectives are the assessment of the impact of PET with gallium on PFS and the evaluation of biomarkers

Study treatment:

FOLFIRI regimen

  • Oxaliplatin (CPT-11) 180 mg/m2, given as 60 min. i.v. infusion on day 1 every 2 weeks followed by
  • Calcio levofolinate 200 mg/m2, given as a 2h i.v. infusion on days 1 every 2 weeks followed by
  • 5-Fluorouracil 400 mg/m2 given as bolus, and then 5-Fluorouracil 2400 mg/m2 given as a 48 h continuous infusion on day 1, every 2 weeks, until progression or for a maximum of 12 cycles

CAPTEM regimen Capecitabine 750 mg/m2 twice a day on days 1-14 in combination with temozolomide 200 mg/m2 daily on days 10-14, every 4 weeks, until progression or for a maximum of 6 cycles.

Being tested
CPT-11, Calcio levofolinate, 5-Fluorouracil, Capecitabine, Temozolomide
Keywords
Neuroendocrine Carcinoma, second line therapy, PET imaging, FOLFIRI, CAPTEM
Medical subject headings
Carcinoma, Neuroendocrine

What participants receive

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

Study groups in NCT03387592
Study groupRoleWhat they receive
FOLFIRI regimenActive comparatorCPT-11 180 mg/m2, given as 60 min. i.v. infusion on day 1 every 2 weeks followed by Calcio levofolinate 200 mg/m2, given as a 2h i.v. infusion on days 1 every 2 weeks followed by 5-Fluorouracil 400 mg/m2 given as bolus, and then 5-Fluorouracil 2400 mg/m2 given as a 48 h continuous infusion on day 1, every 2 weeks, until progression or for a maximum of 12 cycles
Receives: Drug: CPT-11; Drug: Calcio levofolinate; Drug: 5-Fluorouracil
CAPTEM regimenExperimentalCapecitabine 750 mg/m2 twice a day on days 1-14 in combination with Temozolomide 200 mg/m2 daily on days 10-14, every 4 weeks, until progression or for a maximum of 6 cycles
Receives: Drug: Capecitabine; Drug: Temozolomide

What is being measured

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

  1. Disease Control Rate (DCR)

    DCR is defined as the percentage of patients who have achieved complete, partial response and stable disease lasting for at least 12 weeks. DCR will be evaluated using the new international criteria proposed by the Version 1.1 Response Evaluation Criteria in Solid Tumors (RECIST).

    Measured: responses to treatment lasting at least 12 weeks up to 48 months of study period

  2. Incidence of treatment related adverse events

    Acute treatment related adverse events and late treatment related adverse events will be evaluated; the late treatment related adverse events is the adverse event that occurred after 30 days from the last treatment cycle. The adverse events will be evaluated according to CTCAE Version 5.0.

    Measured: up to 60 months

Secondary outcomes (5)

  1. Overall Survival (OS)

    Overall Survival (OS) is defined as the time from treatment start to the time of death from any cause. Subjects who are alive at the time of the final analysis or who have become lost to follow-up will be censored at their last known alive date.

    Measured: up to 60 months

  2. Progression Free Survival (PFS)

    Progression free survival is defined as the time from the start treatment date to the date of first observation of documented disease progression or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation.

    Measured: up to 60 months

  3. Objective response rate (ORR)

    ORR is defined as the percentage of patients who have achieved complete and partial response for at least 12 weeks from therapy start.

    Measured: responses to treatment lasting at least 12 weeks up to 60 months of study period

  4. Quality of Life Questionnaire (QLQ)

    Quality of life will be evaluated through validated standardized data collection forms from the EORTC QLQ-C30 questionnaire (quality of life questionnaire). Scoring of global health status, functional scales and symptom scales will be calculated according to EORTC QLQ-C30 Scoring Manual.

    Measured: up to 60 months

  5. Evaluation of biomarkers

    testing for mutational status of Multiple endocrine neoplasia, type 1 (MEN1), death-domain-associated protein (DAXX), α thalassemia/mental retardation syndrome X-linked (ATRX) and Retinoblastoma 1 (RB-1) on primary tumors tissues and for miRNA on blood samples.

    Measured: up to 60 months

Timeline

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

  1. First posted2 Jan 2018
  2. Study start6 Mar 2017
  3. Primary completion28 Feb 2022
  4. Study completion28 Feb 2022

Why it stopped: Efficacy endpoint not met according to first step of Briant-Day design

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03387592
Sponsor's protocol ID
IRST100.22
Acronym
SENECA
Status last verified
Mar 2022
First submitted
18 Dec 2017
Last updated
10 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Bongiovanni A, Liverani C, Foca F, Bergamo F, Leo S, Pusceddu S, Gelsomino F, Brizzi MP, Di Meglio G, Spada F, Tamberi S, Lolli I, Cives M, Marconcini R, Pucci F, Berardi R, Antonuzzo L, Badalamenti G, Santini D, Recine F, Vanni S, Tebaldi M, Severi S, Rudnas B, Nanni O, Ranallo N, Crudi L, Calabro L, Ibrahim T. A randomized phase II trial of Captem or Folfiri as second-line therapy in neuroendocrine carcinomas. Eur J Cancer. 2024 Sep;208:114129. doi: 10.1016/j.ejca.2024.114129. Epub 2024 May 25.

    PubMed 39002347

  • Bongiovanni A, Liverani C, Pusceddu S, Leo S, Di Meglio G, Tamberi S, Santini D, Gelsomino F, Pucci F, Berardi R, Lolli I, Bergamo F, Ricci S, Foca F, Severi S, Ibrahim T; SENECA Study Team Investigators. Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol. BMJ Open. 2020 Jul 19;10(7):e034393. doi: 10.1136/bmjopen-2019-034393.

    PubMed 32690499

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CPT-11, Calcio levofolinate and 5-Fluorouracil in people with Neuroendocrine Carcinoma, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 23 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 12 inclusion and 16 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: stopped early, as of the sponsor's last update on 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 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?

The study was stopped early (reason given: Efficacy endpoint not met according to first step of Briant-Day design). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Control Rate (DCR) (time frame: responses to treatment lasting at least 12 weeks up to 48 months of study period). The study lists 2 primary outcomes in all. 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 NCT03387592, which also lists 2 linked publications.

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 10 Mar 2025.

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