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

NCT03992911 | Unknown Phase 2

• 1 other identifier: LP-201
• Study Type: interventional
• Target: 336
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuroendocrine Carcinoma of the Bladder

Keywords

Neuroendocrine Carcinoma; Simmtecan; Toripalimab

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Measure of time from study treatment to patient's death or lost to follow-up.

  2 years

Secondary Outcomes (5)

• Progression-free survival

  2 years

• Objective response rate

  2 years

• Disease control rate

  2 years

• Duration of response

  2 years

• The incidence of treatment related emergent adverse events（Safety and Tolerance)

  2 years

Study Arms (2)

FOLFSIM Plus Teripalimab

EXPERIMENTAL

Simmtecan and 5-FU/LV Regimen (FOLFSIM) Plus Teripalimab

Drug: Simmtecan, 5-FU and l-LV; Drug: Toripalimab

EP/EC

ACTIVE COMPARATOR

Etoposide plus Cisplatin or Carboplatin

Drug: Etoposide, Cisplatin; Drug: Etoposide, Carboplatin

Interventions

Simmtecan, 5-FU and l-LV DRUG

Simmtecan was administered intravenously at 80 mg per square meter on day1 with LV 400 mg per square meter administered as a 2-hour infusion, and 5-FU 2400 mg per square meter as a 46-hour infusion on day1 every 2 weeks in one course.

Also known as: FOLFSIM regimen

FOLFSIM Plus Teripalimab

Toripalimab DRUG

Toripalimab was administered intravenously at 240 mg on day 1 every 2 weeks in one course.

Also known as: JS001

FOLFSIM Plus Teripalimab

Etoposide, Cisplatin DRUG

Etoposide was administered intravenously at 100 mg per square meter on day 1,2,3 with Cisplatin at 80 mg per square meter on day 1 every 3 weeks in one course.

Also known as: EP regimen

EP/EC

Etoposide, Carboplatin DRUG

Etoposide was administered intravenously at 100 mg per square meter on day 1,2,3 and Carboplatin with AUC 5mg/mL/min on day 1 every 3 weeks in one course.

Also known as: EC regimen

EP/EC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/ μL; platelets ≥ 100 x 10\^3/ μL; 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), INR≤1.5, APTT≤1.5 x ULN;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

Fluorouracil; toripalimab; PE regimen; EC regimen

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)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lin Shen

  Peking University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lin Shen

CONTACT

86-10-88196561; linshenpku@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor, Chief of Department of GI Oncology, Peking University Cancer Hospital

Study Record Dates

• First Submitted: June 19, 2019
• First Posted: June 20, 2019
• Study Start: June 19, 2019
• Primary Completion: June 20, 2022
• Study Completion: June 20, 2023
• Last Updated: June 20, 2019

Record last verified: 2019-06

Locations

CN (1)