Sintilimab in the Treatment of Advanced and Refractory Pediatric Malignant Tumors

NCT04400851 | Unknown Phase 1

• 1 other identifier: SunYat-sen-Sintilimab
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, single arm, open-label and phase I clinical study. The standard 3 + 3 group design was performed. Patients were enrolled by the design of phase I study standard. Sintilimab was divided into three dose levels: 1 mg / kg, 3 mg / kg, and 10 mg / kg. Dose escalation was carried out from the first level of sintilimab. The study is to evaluate the safety, including dose limited toxicity (DLT) in the treatment of advanced, recurrent, and refractory childhood cancer.

Conditions

Pediatric Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerable dose (MTD)

  Determine the appropriate dose of maximum tolerable dose (MTD) of sintilimab for further clinical study in this patient population

  From date of enrollment until the end of 1 cycle of treatment, assessed up to 3 weeks

Secondary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

• Objective presponse rate (ORR)

  From the date of the treatment to the first evaluation (After 2 cycles of treatment assessed up to 6 weeks)

Study Arms (1)

Sintilimab in advanced childhood cancer patients

EXPERIMENTAL

Drug: Sintilimab

Interventions

Sintilimab DRUG

Patients were enrolled by the design of phase I study standard. Sintilimab was divided into three dosage levels: 1 mg / kg, 3 mg / kg, and 10 mg / kg. The first level of sintilimab was followed by dose escalation

Sintilimab in advanced childhood cancer patients

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: 1-18 years old;
• ECOG PS score: 0-1;
• Pediatric malignant tumors confirmed by histopathology include Hodgkin's lymphoma, mediastinal large B-cell lymphoma, NK / T-cell lymphoma, nasopharyngeal carcinoma, malignant melanoma, neuroblastoma, hepatoblastoma, sarcoma, brain tumor, etc;
• Late stage patients who failed to receive standard treatment;
• There must be at least one measurable lesion defined by RECIST or who standard;
• Estimated survival time ≥ 6 months;
• Heart function:
• LVEF ≥ 50% by color Doppler echocardiography;
• EKG showed no myocardial ischemia;
• There was no history of arrhythmia requiring drug intervention before admission;
• Patients must fully recover from the acute toxicity of all previous anticancer chemotherapy;
• Myelosuppression chemotherapy: at least 21 days after the last myelosuppression chemotherapy (42 days if nitrosourea was used in the earlier stage);
• Experimental drug or anti-cancer therapy other than chemotherapy: it can not be used within the first 28 days before the planned start of the use of sintilimab, and must be clearly recovered from the clinically significant toxicity of the therapy;
• Immunotherapy: at least 42 days after completion of any type of immunotherapy (excluding steroids), including immunocheckpoint inhibitors and tumor vaccines;
• X-ray therapy (XRT): at least 14 days after local palliative XRT (small oral area); in case of other substantial bone marrow (BM) irradiation, including pre radioiodinated m-iodobenzidine (131I-MIBG) treatment, at least 42 days must be ended;

You may not qualify if:

• Received anti-PD-1 or anti-PD-L1 monoclonal antibody or related pathway targeted drugs;
• Known to be allergic to PD-1 monoclonal antibody or any of its adjuvants; known to have a history of allergic diseases or severe allergic constitution;
• Patients with other malignant tumor diseases other than those treated by the Institute, except for patients who has been cured and with no recurrence within 3 years before the study was selected, completely removed basal cell and squamous cell skin cancer, completely removed any type of carcinoma in situ;
• Active central nervous system metastasis (whether or not treated), including symptomatic brain metastasis or meningeal metastasis or spinal cord compression, etc.; except: asymptomatic brain metastasis (no progress within at least 4 weeks after radiotherapy and / or no neurological symptoms or signs after surgical resection, no need for dexamethasone or mannitol treatment).
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage;
• The toxicity of previous treatment is still more than grade 1 (CTCAE V4.03 Standard), except hair loss and neurotoxicity;
• Having a history of mental disorders;
• Those who have a history of drug use or drug abuse upon inquiry;
• History of idiopathic pulmonary fibrosis or pneumonia;
• The complications that need to be treated with immunosuppressive drugs, or the complications that need to be treated with systemic or local corticosteroids according to the dose with immunosuppressive effect (prednisone \> 10 mg / day or equivalent dose of similar drugs).
• Have a history of autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, etc., except for: type I diabetes, hypothyroidism that can be controlled only through hormone replacement therapy, skin diseases that do not need systemic treatment (such as vitiligo, psoriasis), controlled celiac disease, or Disease that does not recur without external stimulus;
• Patients with active TB infection before or now;
• Active infection requiring systemic treatment;
• Uncontrolled hypertension (systolic ≥ 140 mmHg and / or diastolic ≥ 90 MmHg) or pulmonary hypertension or unstable angina pectoris; myocardial infarction or bypass or stent operation within 6 months before administration; history of chronic heart failure meeting NYHA level 3-4; valvular disease of clinical significance; serious arrhythmia requiring treatment (excluding atrial fibrillation and paroxysmal supraventricular tachycardia), including QTc interval male ≥ 450ms , female ≥ 470ms (calculated by friderica formula), cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months before administration, etc;
• Serious medical diseases, including but not limited to: uncontrolled diabetes, active peptic ulcer, active bleeding, etc;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

Yizhuo Zhang

Guangzhou, China

RECRUITING

Related Publications (1)

• Que Y, Wang J, Sun F, Wang S, Zhu J, Huang J, Zhao Z, Zhang L, Liu J, Xu J, Zhen Z, Sun X, Lu S, Zhang Y. Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study. Signal Transduct Target Ther. 2023 Oct 13;8(1):392. doi: 10.1038/s41392-023-01636-9.

  PMID: 37828033 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

sintilimab

Central Study Contacts

Yizhuo Zhang

CONTACT

020-87342459; zhangyzh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 26, 2020
• Study Start: August 11, 2020
• Primary Completion: October 10, 2021
• Study Completion: December 10, 2021
• Last Updated: September 3, 2020

Record last verified: 2020-09

Locations

CN (1)