A Multicenter, Prospective, Double-Cohort Phase II Clinical Study of Camrelizumab in Combination With Docetaxel and Platinum or Apatinib Mesylate as First-Line Treatment for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Camrelizumab
- Conditions
- Recurrent Head and Neck Squamous Cell Carcinoma
- Sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
- Enrollment
- 81
- Locations
- 1
- Primary Endpoint
- Overall Survival (OS) in All Participants
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
This study is the first clinical study of first-line treatment of head and neck squamous cell carcinoma with drugs targeting VEGF signaling pathway combined with PD-1 inhibitors in China, which explores the new combination therapies urgently needed in clinical practice and lays a foundation for subsequent studies, with important scientific research significance and clinical value.
Detailed Description
Head and neck cancer is the sixth most common cancer in the world, with more than 550,000 cases and 300,000 deaths worldwide each year. About 75,000 Chinese suffer from head and neck cancer each year, and currently, there are a total of 176,000 patients with head and neck cancer in China. More than 95% of head and neck cancers are squamous cell carcinomas, and head and neck squamous cell carcinoma (SCCHN) disrupts and affects the patient's appearance and basic physiological functions, sensory functions, and language functions, thus affecting the patient's quality of life. Most head and neck squamous cell carcinomas are incurable, and they will develop local recurrence and metastasis. More than 60% of patients with head and neck squamous cell carcinoma have stage III or IV disease characterized by large size tumors with marked local invasion, evidence of metastasis to regional lymph nodes, or both. Locally advanced head and neck cancer has a high risk of local recurrence and distant metastasis and a poor prognosis. Over the past 20 years, multimodal treatment approaches have steadily improved cure rates while striving to maintain patient function and quality of life. Currently, there are a large number of ongoing clinical trials that combine targeted therapies and immunotherapies. The basic rationale behind these combinations is that they combine different immunological and tumor biological mechanisms to enhance antitumor activity; in addition, some evidence suggests that targeted therapies can enhance certain aspects of the "cancer-immune cycle" (e.g., tumor antigenicity, T cell priming/trafficking/infiltration, etc.) to synergistically enhance immunotherapy. This clinical study involved Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection (Camrelizumab), a Class 1 new therapeutic biological product developed by Jiangsu Hengrui Medicine Co., Ltd., which was approved by NMPA in May 2019 for the treatment of relapsed or refractory classical Hodgkin's lymphoma, by NMPA in March 2020 for the treatment of patients with advanced hepatocellular carcinoma who have received sorafenib and/or oxaliplatin-based systemic chemotherapy, and in June 2020 for the second-line treatment of esophageal squamous cell carcinoma and first-line treatment of non-squamous non-small cell lung cancer. Preclinical study data showed that camrelizumab had comparable in vivo efficacy and safety compared with similar drugs abroad. Since 2015, Hengrui has simultaneously carried out a number of phase I/II clinical trials in Australia and China to preliminarily verify the safety, tolerability and efficacy of camreibizumab in the treatment of advanced solid tumors. This clinical study also involved apatinib mesylate developed by Jiangsu Hengrui Medicine Co., Ltd. and marketed in 2014. Apatinib mesylate is a small molecule targeted drug, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, which exerts anti-angiogenic effect mainly by inhibiting VEGFR to treat malignant tumors. Preclinical studies have shown that its anti-tumor effect is superior to that of similar drugs. In 2014, apatinib mesylate has been used in patients with advanced gastric or gastro-esophageal junction adenocarcinoma who have progressed or relapsed after at least 2 prior systemic chemotherapies.
Investigators
ren guoxin
Dr.
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Eligibility Criteria
Inclusion Criteria
- •Newly diagnosed recurrent or metastatic head and neck squamous cell carcinoma which is histologically or cytologically confirmed, and unable to be cured by local treatment (the primary site of the tumor is the oropharynx, oral cavity, hypopharynx and larynx), recurrence or metastasis stage did not receive any anti-tumor systemic therapy (allowed as part of the treatment of locally advanced tumors, and it has been more than 6 months from the end of treatment to signing the informed consent);
- •ECOG score of 0 or 1;
- •At least one measurable lesion according to RECIST1.1 criteria.
- •Tumor tissue with PD-L1 detection (paraffin specimens or fresh tumor tissue within 2 years) can be provided; Patients with Oropharyngeal cancer should provide P16 detection status by using IHC method;
- •Patients with a history of brain/meningeal metastasis must be treated with local therapy (surgery/radiotherapy) before the start of the study, and clinically stable for at least 3 months (corticosteroids are allowed before the first dose of the study drug, but need to be discontinued 2 weeks before the start of the study drug); The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up.
Exclusion Criteria
- •Progression within 6 months after systemic treatment for locally advanced head and neck squamous cell carcinoma;
- •Previous history of primary tumor of nasopharyngeal carcinoma;
- •Intolerable to platinum-based therapy;
- •Previous treatment with platinum-based regimen and disease progression;
- •Patients who participated in or were participating in other drug/therapy clinical trials 4 weeks before the first dose of study drug;
- •Patients who underwent major surgery or had not recovered from the side effects of this surgery; Patients who has accepted live vaccination, immunotherapy, or patients who underwent radiotherapy within 2 weeks;
- •Patients who received any other anti-tumor treatment;
- •Patients who are using immunosuppressive agents, or systemic hormone therapy to achieve the purpose of immunosuppression (dose \> 10 mg/day prednisone or other effective hormones), and continue to use 2 times before enrollment;
- •History of other malignant tumors within the past 5 years, except cured cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, early prostate cancer and cervical carcinoma in situ;
- •Patients who have received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin and other treatments before the first dose of study drug;
Arms & Interventions
Camrelizumab + Chemotherapy
Participants receive Camrelizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 24 months;plus cisplatin 75 mg/m\^2 IV or carboplatin at a target area under the curve of 5 (AUC 5) IV, per Investigator's choice, on Day 1 of each 3-week cycle (6 cycle maximum); plus docetaxel 75 mg/m\^2 IV on Day 1 of each 3-week cycle (6 cycle maximum).
Intervention: Camrelizumab
Camrelizumab + Chemotherapy
Participants receive Camrelizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 24 months;plus cisplatin 75 mg/m\^2 IV or carboplatin at a target area under the curve of 5 (AUC 5) IV, per Investigator's choice, on Day 1 of each 3-week cycle (6 cycle maximum); plus docetaxel 75 mg/m\^2 IV on Day 1 of each 3-week cycle (6 cycle maximum).
Intervention: Cisplatin
Camrelizumab + Chemotherapy
Participants receive Camrelizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 24 months;plus cisplatin 75 mg/m\^2 IV or carboplatin at a target area under the curve of 5 (AUC 5) IV, per Investigator's choice, on Day 1 of each 3-week cycle (6 cycle maximum); plus docetaxel 75 mg/m\^2 IV on Day 1 of each 3-week cycle (6 cycle maximum).
Intervention: Docetaxel
Camrelizumab + Chemotherapy
Participants receive Camrelizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 24 months;plus cisplatin 75 mg/m\^2 IV or carboplatin at a target area under the curve of 5 (AUC 5) IV, per Investigator's choice, on Day 1 of each 3-week cycle (6 cycle maximum); plus docetaxel 75 mg/m\^2 IV on Day 1 of each 3-week cycle (6 cycle maximum).
Intervention: Carboplatin
Camrelizumab +Apatinib mesylate
Participants receive Camrelizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 24 months;plus Apatinib 250mg qd for up to 24 months.
Intervention: Camrelizumab
Camrelizumab +Apatinib mesylate
Participants receive Camrelizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 24 months;plus Apatinib 250mg qd for up to 24 months.
Intervention: Apatinib Mesylate
Outcomes
Primary Outcomes
Overall Survival (OS) in All Participants
Time Frame: 12 months
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.
Secondary Outcomes
- DOR in Participants With PD-L1 CPS ≥1(24 months)
- Number of Participants Experiencing an Adverse Event (AE).(12 months)
- Quality of life（EORTC QLQ-C30 scale）(12 months)
- Objective Response Rate Per RECIST 1.1(12 months)
- Duration of Response Per RECIST 1.1(24 months)
- ORR in Participants With PD-L1 CPS ≥1(12 months)
- Progression Free Survival Per RECIST 1.1(12 months)
- ORR in Participants With PD-L1 CPS ≥20(12 months)
- DOR in Participants With PD-L1 CPS ≥20(12 months)