Overview

CAPTEM or FOLFIRI as SEcond-line Therapy in NEuroendocrine CArcinomas

Status:
Recruiting
Trial end date:
2022-01-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Treatments:
Capecitabine
Fluorouracil
Leucovorin
Levoleucovorin
Temozolomide
Criteria
Inclusion Criteria:

1. 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.

2. Male or Female, aged >=18 years.

3. Measurable disease according to RECIST 1.1 criteria.

4. 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).

5. Previous treatments with immuno checkpoint-inhibitor and/or everolimus are permitted

6. Life expectancy greater than 3 months

7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

8. 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.

9. 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.

10. 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.

11. Brain metastases allowed if asymptomatic at study baseline. Whole brain irradiation or
focal treatment for Central Nervous System (CNS) metastases are permitted.

Exclusion Criteria:

1. Ki67 index ≤ 20 %.

2. Patients with metastatic NECs already treated with irinotecan regimen.

3. Patients with a known hypersensitivity to fluorouracil or calcium levofolinate or
Irinotecan or their recipients.

4. 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).

5. Life expectancy minor than 3 months.

6. ECOG performance status >2.

7. Participation in another clinical trial with any investigational agents within 30 days
prior to study screening.

8. 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

9. History of allergic reactions attributed to compounds of similar chemical or biologic
composition.

10. 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

11. 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

12. Other malignancy with a disease-free interval of less than 5 years (except non
melanoma skin cancer or low grade superficial bladder cancer).