A Phase 3 Study to Evaluate Surufatinib Plus Toripalimab in the Treatment of Advanced Neuroendocrine Carcinoma

NCT05015621 | Unknown Phase 3 DMC

• 1 other identifier: 2021-012-00CH1
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy of Surufatnib combined with Toripalimab compared with FOLFIRI in the treatment of advanced neuroendocrine carcinoma

Conditions

Advanced Neuroendocrine Carcinoma

Keywords

secondline treatment in patients

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Duration from the date of initial treatment to the date of death due to any cause.

  From date of first dose of study drug until withdrawal of consent or death (up to approximately 2 years)

Secondary Outcomes (7)

• Progression-free Survival (PFS) (RECIST1.1)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 2 years)

• Objective response rate (ORR)(RECIST1.1)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy(up to approximately 2 years)]

• Duration of response (DoR)(RECIST1.1)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)]

• Disease control rate (DCR)(RECIST1.1)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)]

• PD-L1

  Baseline (before the randomization)

Study Arms (2)

study group

ACTIVE COMPARATOR

all subjects will receive study treatment in 21-day cycle, Surufatinib 250mg, QD and Toripalimab, 240mg, IV drip, Q3W, D1, the treatment will continue until one of the following conditions occurs: progression of disease, death, intolerable toxicity, or the end of study treatment (as other criteria specified in the protocol are met), whichever occurs first

Drug: Surufatinib plus Toripalimab

control group

OTHER

FOLFIRI group subjects will receive study treatment in 14- day cycle, Irinotecan: 180 mg/m\^2, iv drip over 30～90 minutes, on Day 1; Calcium folinate: 400 mg/m\^2, iv drip for about 2 hours, given upon completion of infusion of Irinotecan on Day 1; 5-FU: 400 mg/m\^2, iv bolus, given upon completion of infusion of Calcium folinate on Day 1, followed by 2400 mg/m\^2 continuously iv drip for 46～48 hours.

Drug: 5-fluorouracil, Calcium folinate and Irinotecan

Interventions

Surufatinib plus Toripalimab DRUG

Surufatinib is a tablet in the form of 50mg, oral, once a day; Toripalimab is an injection in the form of 240mg, intravenous, once three weeks.

Also known as: HMPL-012 plus JS001

study group

5-fluorouracil, Calcium folinate and Irinotecan DRUG

Irinotecan 180 mg/m\^2, Calcium folinate 400 mg/m\^2, 5-FU total 2800 mg/m\^2 will be administrated once two weeks.

Also known as: FOLFIRI

control group

Eligibility Criteria

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

You may qualify if:

• Patients who included in this study must fulfil all of the following criteria:
• Fully aware of this study and voluntary to sign the informed consent form (the informed consent form must be signed before any trial-specific procedure is performed);
• Aged 18\~75 years (inclusive);
• Histologically or cytologically confirmed, unresectable, locally advanced or metastatic neuroendocrine carcinoma
• Patients with neuroendocrine carcinoma who have failed previous platinum-based 1st-line chemotherapy
• ECOG performance status of 0 or 1 ;
• Having clear measurable lesions as defined by RECIST v1.1;
• Patients who agree to provide tumor specimens for pathological type review and biomarkers detection;
• Patients with adequate bone marrow, liver and kidney organ functions whose laboratory tests within 7 days before the first dose meet the following requirements:
• Absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥100×109/L and hemoglobin ≥90 g/dL (without blood transfusion or use of blood products for correction within 14 days prior to laboratory examination, and without use of granulocyte colony stimulating factor or other hematopoietic stimulating factor for correction within 7 days prior to laboratory examination);
• Serum total bilirubin ≤1.5 × upper limit of normal (ULN);
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 × ULN in the absence of liver metastases; ALT and AST ≤5 × ULN in the presence of liver metastases.
• Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min (calculated according to the Cockcroft-Gault formula, see Appendix 3);
• Routine urinalysis showing urine protein \< 2+; in case of urine protein ≥ 2+, 24-hour urine protein (quantitative) should be \<1g;
• International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤1.5 × ULN.

You may not qualify if:

• Subjects must be excluded from this study when any one of the following criteria is met:
• Toxicities associated with previous anti-tumor treatment do not return to ≤CTCAE grade 1, except for alopecia and peripheral neurotoxicity (≤ CTCAE grade 2 ) caused by Oxaliplatin;
• Presence of other malignancies in the past 5 years (except for basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix, which were effectively controlled);
• Presence of central nervous system (CNS) metastases in screening period;
• Use of approved systematic anti-tumor therapy within 4 weeks prior to the first dose, including chemotherapy, biotherapy, targeted therapy (the washout period of small molecular targeted drugs lasts 2 weeks or 5 half-lives, whichever is shorter), hormone therapy, treatments with traditional Chinese medicine (for patients receiving treatments with traditional Chinese medicine with clear anti-tumor indications, for anti-tumor indications clearly specified in the package insert, one-week washout period prior to the first dose is acceptable), etc.;
• Use of radical radiotherapy (including radiotherapy for more than 25% of the bone marrow) within 4 weeks before the first dose; brachytherapy (e.g. radioactive particle implantation) within 60 days prior to the first dose; palliative radiotherapy for bone metastases within 1 week before the first dose;
• Previous use of anti (PD-1), anti-PD-L1, anti-PD-L2 or CTLA-4 antibody or any other antibody acting on T cell co-stimulatory or checkpoint pathways
• Previous use of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) targeted therapy;
• Previous therapy with Irinotecan;
• Having abnormal thyroid function with symptoms ongoing or requiring treatment at screening ;
• Use of immunosuppressant within 4 weeks prior to the first dose, not including local glucocorticoid via nasal spray, inhalation or other routes or systemic glucocorticoid at physiological dose (i.e., no more than 10mg/day of prednisone or equivalent dose), temporary use of glucocorticoid for treatment of dyspnea resulted from asthma, chronic obstructive pulmonary disease is allowed, and preventive use of corticosteroid to avoid allergic reactions is allowed
• Patients with any active autoimmune disorders requiring systematic treatment or a history of autoimmune disease in the past 2 years,
• Use of systemic immune stimulants within 4 weeks prior to the first dose;
• Vaccination of any live or attenuated live vaccine within 4 weeks prior to the first dose or during the study.
• Patients having received major surgical operation within 4 weeks prior to the first dose .

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

MeSH Terms

Interventions

surufatinib; toripalimab; Fluorouracil; Leucovorin; Irinotecan; IFL protocol

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids

Study Officials

• Lin Shen, Prof.

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Panfeng Tan

CONTACT

+86 21 2067 1828; panfengt@hutch-med.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2021
• First Posted: August 20, 2021
• Study Start: September 18, 2021
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: December 13, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)