Efficacy and Safety of Neoadjuvant Surufatinib for Patients With Salivary Gland Carcinomas

A Study of Surufatinib Neoadjuvant Therapy for Locally Advanced Primary Saliary Gland Adenocarcinoma：a Single-arm, Prospective,Open Label Study

The objective is to investigate the efficacy and safety of Surufatinib Neoadjuvant Therapy for Locally Advanced Primary Saliary Gland Adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Salivary Gland Carcinomas
• Intervention / Treatment: Drug: Surufatinib

Detailed Description

The purpose of this study was to explore whether the efficacy and survival time of patients with local advanced primary salivary gland adenocarcinoma could be further improved through the treatment of Surufatinib neoadjuvant for local advanced primary salivary gland adenocarcinoma, and to explore the safety and tolerability of this regimen.A Study of Surufatinib Neoadjuvant Therapy for Locally Advanced Primary Saliary Gland Adenocarcinoma：a Single-arm, Prospective,Open Label Study.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Min Ruan, MD; Phone Number: 15150667249; Email: doctorruanmin@sjtu.edu.cn
• Study Contact Backup: Name: Shuyang Sun, MD; Phone Number: 18019790962; Email: sunshuyang@sjtu.edu.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
    • Contact: Min Ruan, MD; Phone Number: 15150667249; Email: doctorruanmin@sjtu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of written Informed Consent Form (ICF) prior to any study specific procedures;
2. aged between 18 and 75 years are eligible;
3. Male and Female are available；
4. Patients with locally advanced primary salivary gland adenocarcinoma confirmed by pathology or histology (except nasopharyngeal carcinoma);At least one measurable lesion (≥10mm on spiral CT scan, meeting RECIST 1.1 criteria);
5. Patients have not received chemotherapy or radiotherapy, targeted therapy, or surgery for any previous reason;
6. Patients with indications for surgery；
7. Primary TNM stage Ⅲ-ⅣA (T1-2/N1-2/M0 or T3-4A/CN0-2 /M0, AJCC2018);
8. Patients should not be accompanied by any other anticancer therapy;
9. It is not concomitant with long-term treatment (≥3 months) with ≥20mg daily dose of methylprednisolone or equivalent dose of corticosteroids;
10. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
11. Predicted survival ≥12 weeks;

12. Screening laboratory values must meet the following criteria (within past 14 days):

    • neutrophils ≥3.0×109/L ;
    • platelets ≥100×109/L；
    • hemoglobin ≥ 9.0 g/dL;
    • albumin≥3g/dL；
    • 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; Endogenous creatinine clearance >50ml/min (Cockcroft- Gault formula);
13. Males or female of childbearing potential must: agree 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 6 months after the last dose of study drug.

Exclusion Criteria:

1. Prior treatment with Surufatinib,or other antiangiogenic drugs were used within 6 months;
2. Prior antitumor therapy with chemotherapy, radical radiation therapy ，biological immunotherapy，targeted therapy within 4 weeks.
3. Prior participation in other clinical trials not approved or listed in China within past 4 weeks；
4. Prior major surgery within past 4 weeks (Venous catheterization, puncture and drainage are excluded);
5. International standardized ratio (INR) >1.5 or partially activated prothrombin time (APTT) >1.5×ULN;
6. Clinically significant severe electrolyte abnormality judged by investigator ;
7. Hypertension that is not controlled by the drug, and is defined as: SBP≥140 mmHg and/or DBP≥90 mmHg;
8. Currently suffering from poorly controlled diabetes (after regular treatment, fasting plasma glucose concentration ≥10mmol/L);
9. The patient currently has disease or condition that affects the absorption of the drug, or the patient cannot be administered orally;
10. Digestive tract disease such as gastric and duodenal active ulcer, ulcerative colitis or unresected tumor, or other conditions determined by the investigator that may cause gastrointestinal bleeding and perforation;
11. Evidence of bleeding tendency or history within 3 months, or thromboembolic event (including a stroke event and/or a transient ischemic attack) occurred within 12 month;
12. Cardiovascular disease of significant clinical significance (myocardial infarction, unstable arrhythmia or unstable angina ，Coronary Artery Bypass Grafting within past 6 months,)；
13. Had other malignant tumors in the past 5 years (except for basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ that have been effectively controlled);
14. Active or uncontrolled severe infection (≥CTCAE2 infection);
15. Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (>2000IU/ml);
16. Evidence with active CNS disease or previous brain metastases;
17. The toxicity associated with previous anti-tumor treatment has not recovered to ≤CTCAE1, except for peripheral neurotoxicity and alopecia ≤CTCAE2 caused by oxaliplatin;
18. Pregnant or nursing;
19. Transfusion therapy, blood products and hematopoietic factors, such as albumin and granulocyte colony stimulating factor (G-CSF), had been received within 14 days before enrollment;
20. Tumor involving skin and/or pharyngeal mucosa with ulceration;
21. Patients with a history of psychotropic drug abuse and unable to quit or with mental disorders;
22. Any other disease, with clinical significance of metabolic abnormalities, abnormal physical examination or laboratory abnormalities, according to researchers, there is reason to doubt is not suitable for the use of study drugs in patients with a disease or condition (such as have a seizure and require treatment), or will affect the interpretation of results, or make the patients at high risk.
23. Routine urine indicated that urine protein ≥2+, and the 24-hour urine protein volume >1.0g;
24. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Salivary Gland Carcinomas; Patients with Salivary Gland Carcinomas were given Surufatinib .

Drug: Surufatinib; Patients receive oral Surufatinib at a dose of 300mg/d (once-daily dosing continuously, every 28-day treatment cycle), A total of 2 cycles were performed, and efficacy evaluation was performed at the end of each cycle or was determined to be required by the investigator. If disease progression or unacceptable toxicity occurred during the period, induction therapy was terminated early, and after corresponding treatment, surgical treatment was entered as early as possible. Surufatinib treatment was interrupted 4-7 days before surgical treatment to maintain organ function; Note: Postoperative radiotherapy or chemoradiotherapy is permitted after radical surgery at the discretion of the investigator.; Other Names: radiotherapy or chemoradiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	CR + PR rate according to the RECIST version 1.1 guidelines.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the anti-tumor activity:DCR	Disease control rate (DCR):CR + PR + SD rate according to the RECIST version 1.1 guidelines.	up to 12 months
Major pathological response rate (MPR)	the reduction of the active tumor below an established clinically significant node.	up to 12 months
Progression Free Survival (PFS)	To assess the efficacy of Neoadjuvant Surufatinib for Patients With Salivary Gland Carcinomas, patients by assessment of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).	up to 36 months
Overall survival time	OS was calculated from the date of pharmacy to death from any cause.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• Investigators: Principal Investigator: Min Ruan, MD, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Mouth Neoplasms; Carcinoma; Salivary Gland Neoplasms
• Other Study ID Numbers: HMPL-012-SPRING-HNC101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No