Safety and Efficacy of FOLFSIM Plus Toripalimab in the Treatment of Advanced or Metastatic Neuroendocrine Carcinoma

  • End date
    Jun 20, 2023
  • participants needed
  • sponsor
    Peking University
Updated on 23 January 2021


This study is designed as Phase II/III. Phase II is aimed to evaluate safety and efficacy of Simmtecan and the 5-FU/LV regimen (FOLFSIM regimen) plus Toripalimab. Phase III is aimed to verify inferiority of the overall survival of FOLFSIM regimen plus Toripalimab in comparison with EP/EC in advanced or metastatic neuroendocrine cancer.


This is a Phase II/III, randomized, two-part, multi-center study, in which subjects with advanced or metastatic neuroendocrine carcinoma will be enrolled.

This study will be conducted in two parts:

Part 1, the Phase II study was to: (i) evaluate the safety and tolerability of the FOLFSIM regimen plus Toripalimab; and (ii) identify the recommended dose; (iii) assess the antitumor activity; (iv) the pharmacokinetic (PK) parameters of the drugs in the regimen.

Part 2, the Phase III study was to verify inferiority of FOLFSIM regimen plus Toripalimab compared with the current standard chemotherapy (EP/EC regimen) in the first-line treatment of advanced or metastatic neuroendocrine carcinoma.

Condition Neuroendocrine Carcinoma of the Bladder
Treatment Toripalimab, Simmtecan, 5-FU and l-LV, Etoposide, Cisplatin, Etoposide, Carboplatin
Clinical Study IdentifierNCT03992911
SponsorPeking University
Last Modified on23 January 2021


Yes No Not Sure

Inclusion Criteria

Signed informed-consent form
Male and Female aged between 18-75 years
Histologically confirmed locally advanced or metastatic nonfunctional poorly-differentiated G3 neuroendocrine carcinoma(NEC), including small cell NEC, large cell NEC and MANEC
Unresectable, including local advanced, recurrent or metastatic disease
Patients who had progressed after first-line platinum-based regimen or
intolerance for treatment, or unwilling to receive current standard
chemotherapy (only for phase II); Patients who has received no systemic
chemotherapy, or relapsed at least 6 months since completion of adjuvant
chemotherapy or radiotherapy
\. At least 1 measurable lesion according to RECIST criteria
\. Providing with tumor specimen (for testing the expression of PD L1 and the
infiltrating lymphocytes)
\. Eastern Cooperative Oncology Group (ECOG) 0-1
\. Adequate liver, kidney and bone marrow function; Screening laboratory
values must meet the following criteria: hemoglobin 10.0 g/dL neutrophils 1500
cells/ L platelets 100 x 10^3/ L total bilirubin 1.5 x upper limit of normal
(ULN) aspartic transaminase (AST) and alanine transaminase (ALT) 2.5 x ULN
without, and 5 x ULN with hepatic metastasis serum creatinine 1.5 x ULN
creatinine clearance >60ml/min (CockcroftGault equation), INR1.5, APTT1.5 x

Exclusion Criteria

Histologically confirmed well differentiated G3 neuroendocrine tumor
Evidence with active CNS disease or epilepsy
Metastasis over 5 lesions
Prior treatment with CPT-11 or antiPD1/PDL1/CTLA-4 antibody for neoadjuvant or adjuvant therapy
Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix
Predicted survival <3 months
Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure > class II NYHA, heart block >II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm)
Any uncontrollable active infection, within past 1 week
Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism
History with tuberculosis
The side effects caused by the previous treatment of the subjects did not return to CTCAE 1; except hair loss and other tolerable events determined by investigator
Hypersensitivity to Simmtecan or recombinant humanized antiPD1 monoclonal Ab or its components
Prior antitumor therapy (including chemotherapy, target therapy, corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment
Patients who received a potent inhibitor or inducer of CYP3A4 within 1 week prior to the first dose
Prior radical radiothearpy within past 4 weeks
Prior major surgery within past 4 weeks (diagnostic surgery excluded)
Prior live vaccine therapy within past 4 weeks
Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (>500IU/ml)
Pregnant or nursing
Males or female of childbearing potential refuse to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 12 months after the last dose of study drug
Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events
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