Toripalimab Combined With Surufatinib for Locally Advanced Thyroid Cancer: a Phase II Study

NCT04524884 | Unknown Phase 2 DMC

• 1 other identifier: Thca-NEO-ST
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the efficacy and safety of the combination of Toripalimab and Surufatinib for Locally Advanced Thyroid Cancer.

Conditions

Thyroid Cancer

Keywords

Toripalimab; Surufatinib; Thyroid cancer; Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective Response Rate

  16 months after the last patient enrolled

Secondary Outcomes (6)

• R0/1 resection rate

  Within one week after operation

• DCR

  16 months after the last patient enrolled

• TTR

  16 months after the last patient enrolled

• PFS

  16 months after the last patient enrolled

• OS

  16 months after the last patient enrolled

Study Arms (3)

Cohort A

EXPERIMENTAL

Surufatinib 250mg will be taken orally once daily continuously through a 21-day cycle of study treatment. Toripalimab 240mg will be intravenously administered on Day 1 of each cycle. After neoadjuvant Toripalimab and Surufatinib treatment, the patients will receive operation treatment if the tumor is evaluated as resectable cases by clinical examination.

Drug: Surufatinib; Drug: Toripalimab

Cohort B

EXPERIMENTAL

Surufatinib 250mg will be taken orally once daily continuously through a 21-day cycle of study treatment. Toripalimab 240mg will be intravenously administered on Day 1 of each cycle. After neoadjuvant Toripalimab and Surufatinib treatment, the patients will receive further drug reatment, if the tumor is evaluated as unresectable cases and patients have potential benefits by clinical examination.

Drug: Surufatinib; Drug: Toripalimab

Cohort C

EXPERIMENTAL

Surufatinib 250mg will be taken orally once daily continuously through a 21-day cycle of study treatment. Toripalimab 240mg will be intravenously administered on Day 1 of each cycle. After neoadjuvant Toripalimab and Surufatinib treatment, the patients will be removed from the study, if the tumor is evaluated as unresectable cases and patients have no potential benefits by clinical examination.

Drug: Surufatinib; Drug: Toripalimab

Interventions

Surufatinib DRUG

Surufatinib is a tablet in the form of 50mg, oral, once a day.

Also known as: HMPL-012

Cohort A; Cohort B; Cohort C

Toripalimab DRUG

Toripalimab is an injection in the form of 240mg, intravenous, once three weeks.

Also known as: JS001

Cohort A; Cohort B; Cohort C

Eligibility Criteria

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

You may qualify if:

• The patient volunteered to participate in the study and signed an informed consent form and shows good compliance;
• Age ≥18 years, male or female;
• Pathologically diagnosed locally advanced differentiated thyroid cancer, including papillary thyroid cancer and follicular thyroid cancer;
• Diagnosis of locally advanced disease should meet at least one of the criteria:1)Unresectable locally advanced lesion; 2)Difficult to achieve R0/R1 resection during preoperative assessment; 3)AJCC T4 stage: Primary tumor with invasion or adhesion of at least one of the following structures / organs, including: trachea, esophagus, common carotid artery, larynx, anterior vertebral fascia, brachial plexus;
• Have at least one measurable lesion (RECIST 1.1);
• Eastern Cooperative Oncology Group (ECOG) score 0-2;
• Expected survival time ≥ 12 weeks;
• If the patient presents with distant metastasis, the value of local treatment should be assessed by the investigator;
• The patient volunteered to receive tumor biopsy/surgery during rull-in and rull-out periods.
• The main organ functions meet the following criteria within 7 days before treatment:1)Standard blood test (without blood transfusion within 14 days):Hemoglobin (HB) ≥90g / L; Absolute neutrophil value (ANC) ≥ 1.5 × 109 / L; Platelet (PLT) ≥80 × 109 / L; 2)Biochemical inspection must meet the following standards: Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN, if with liver metastases, ALT and AST ≤ 5 ULN; Serum creatinine (Cr) ≤ 1.5 ULN or creatinine clearance (CCr)\>50ml / min; 3)International normalized ratio (INR) ≤2.3 or prothrombin time (PT) prolongs less than 6 seconds; 4)Urine routine indicates urinary protein \<++, and the 24-hour urine protein quantification is less than 1.0 g.
• Women of childbearing age should agree to use contraceptives during the study; negative serum or urine pregnancy tests within 14 days before study enrollment.

You may not qualify if:

• Use any anti-tumor treatment within 4 weeks (28 days) prior to the start of the study treatment, except for TSH suppression treatment;
• Previously used any immune checkpoint inhibitors, including but not limited to pembrolizumab, nivolumab, camrelizumab, sintilimab and etc;
• With other uncontrolled cardiac symptoms or disease;
• Patients whose blood pressure is still unsatisfactory with a blood pressure medication (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg) or a history of hypertensive encephalopathy or hypertensive crisis;
• Those who have multiple factors (such as inability to swallow) that affect oral medication;
• Patients with a gastrointestinal bleeding tendency including 1)Active peptic ulcer; 2)Fecal occult blood ≥ ++; 3)A history of hematemesis or melena within 3 months;
• Coagulation disorder, such as INR greater than 1.5, or activated partial thromboplastin time (APTT) greater than 1.5 \* ULN;
• Significant hemoptysis within 2 months before screening, or the daily volume of hemoptysis reached half a teaspoon (2.5ml) or more;
• Patients whose imaging showed that the tumor had invaded the important blood vessels or the researchers judged that the tumor was likely to invade important blood vessels during the subsequent study period and caused fatal bleeding;
• Arterial / venous thrombosis events, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis and pulmonary embolism within 6 months;
• Patients suffering from interstitial pneumonia or ILD, or with a history of interstitial pneumonia or ILD requiring hormone therapy, or with other pulmonary fibrosis，organic pneumonia(e.g., obliterative bronchiolitis), pneumoconiosis, drug-induced pneumonia and idiopathic pneumonia that may interfere with the diagnosis and management of immune-related pulmonary toxicity; or patients with CT image indicating active pneumonia or severely impaired pulmonary function during screening. Radiation pneumonia is acceptable in the radiation field. Patients with active tuberculosis will be excluded;
• Active autoimmune disease or history of autoimmune disease with recurrence potential (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis): Patients with skin diseases that do not require systemic treatment such as vitiligo, psoriasis, hair loss, controlled type I diabetes receiving insulin therapy; childhood asthma that is completely relieved, or those who do not need any intervention in adulthood can be included; Patients with asthma who undergo medical intervention such as bronchiectasis, cannot be included;
• Use immunosuppressive agents or systemic hormone therapy within preceding 14 days before the study starts to achieve the purpose of immunosuppression (dose\>10mg/day prednisone or hormones with equivalent effects);
• Patients who received strong CYP3A4/CYP2C19 inducer including rifampin (and its analogs) and hypericum perforatum or strong CYP3A4/CYP2C19 inhibitor within preceding 14 days;
• Patients who have a history of severe allergies to any monoclonal antibody or anti-angiogenic targeted drugs;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

270 Dongan Road, Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

surufatinib; toripalimab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Qing-Hai Ji, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

• Yu-Long Wang, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu-Long Wang, MD

CONTACT

+86-18017317225; yulongwang@fudan.edu.cn

Qing-Hai Ji, MD

CONTACT

headneck@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 24, 2020
• Study Start: October 1, 2020
• Primary Completion: April 30, 2022
• Study Completion: September 30, 2022
• Last Updated: August 24, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)