CAPTEM or FOLFIRI as SEcond-line Therapy in NEuroendocrine CArcinomas

NCT03387592 | Terminated Phase 2

• 1 other identifier: IRST100.22
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 23

Brief 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. 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.

Conditions

Neuroendocrine Carcinoma

Keywords

Neuroendocrine Carcinoma; second line therapy; PET imaging; FOLFIRI; CAPTEM

Outcome Measures

Primary Outcomes (2)

• 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).

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

• 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.

  up to 60 months

Secondary Outcomes (5)

• Overall Survival (OS)

  up to 60 months

• Progression Free Survival (PFS)

  up to 60 months

• Objective response rate (ORR)

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

• Quality of Life Questionnaire (QLQ)

  up to 60 months

• Evaluation of biomarkers

  up to 60 months

Study Arms (2)

FOLFIRI regimen

ACTIVE COMPARATOR

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

Drug: CPT-11; Drug: Calcio levofolinate; Drug: 5-Fluorouracil

CAPTEM regimen

EXPERIMENTAL

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

Drug: Capecitabine; Drug: Temozolomide

Interventions

CPT-11 DRUG

180 mg/m2

FOLFIRI regimen

Calcio levofolinate DRUG

200 mg/m2

FOLFIRI regimen

5-Fluorouracil DRUG

400 mg/m2 + 2400 mg/m2

FOLFIRI regimen

Capecitabine DRUG

1500 mg/m2

CAPTEM regimen

Temozolomide DRUG

200 mg/m2

CAPTEM regimen

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

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

Study Sites (23)

Az. Osp. Ospedali Riuniti di Ancona

Ancona, AN, 60020, Italy

Location

A.O.U. Policlinico di Bari

Bari, BA, 70124, Italy

Location

IRCCS IST. Tumori Bari - Giovanni Paolo II

Bari, BA, 70124, Italy

Location

Ospedale di Feltre

Feltre, Belluno, 32032, Italy

Location

ASST Spedali Civili di Brescia

Brescia, BS, 25123, Italy

Location

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

Meldola, FC, 47014, Italy

Location

AOU Careggi

Florence, FI, 50134, Italy

Location

Istituto Europeo di Oncologia

Milan, MI, Italy

Location

Istituto Nazionale Tumori Milano

Milan, MI, Italy

Location

Azienda Ospedaliera-Universitaria di Modena

Modena, MO, Italy

Location

Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

Palermo, PA, 90127, Italy

Location

Centro di Riferimento Oncologico di Aviano

Aviano, Pordenone, 33081, Italy

Location

Ospedale Civile degli Infermi

Faenza, RA, Italy

Location

Policlinico Campus Biomedico Roma

Roma, RM, 00128, Italy

Location

AOU San Luigi Gonzaga

Orbassano, TO, 10043, Italy

Location

Azienda Ospedaliere Universitaria Integrata Verona

Verona, VR, 37134, Italy

Location

Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Ospedale di Bolzano

Bolzano, Italy

Location

IRCCS "Saverio De Bellis"

Castellana Grotte, Italy

Location

Ospedale "Vito Fazzi"

Lecce, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Azienda Ospedaliera-Universitaria di Parma

Parma, Italy

Location

Ospedale S.Chiara - AOU Pisana

Pisa, Italy

Location

Related Publications (2)

• 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.

  PMID: 39002347 DERIVED

• 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.

  PMID: 32690499 DERIVED

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

Irinotecan; Fluorouracil; Capecitabine; Temozolomide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles

Study Officials

• Toni Ibrahim, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: January 2, 2018
• Study Start: March 6, 2017
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: March 10, 2025

Record last verified: 2022-03

Locations

IT (23)