Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Head and Neck Squamous Cell Carcinoma, Neoadjuvant therapy, Immunotherapy, CDK4/6 inhibitor
Brief summary
The purpose of this study is to explore the safety and feasibility of anti-programmed cell death protein 1(PD-1) immunotherapy, Camrelizumab, combined with cyclin-dependent kinase 4/6 blockade, Dalpiciclib, as a new neoadjuvant treatment regimen for patients with resectable head and neck squamous cell carcinoma(HNSCC).
Detailed description
Head and Neck Squamous Cell Carcinoma (HNSCC) is the most common malignancies of the head and neck, accounting for 90% of head and neck cancer. The 5-year survival rate under standard treatment is only 50%. 70%\ 80% of first diagnosed patients already developed into locally advanced status (stage II-Iva). In recent years, the use of neoadjuvant therapy (NAC) followed by surgery or radiotherapy has been advocated because of its higher probability of local/regional failure and distant metastasis after treatment. TPF (Docetaxel + Cisplatin + Fluorouracil) regimen is considered as the standard regimen of induced chemotherapy for head and neck squamous cell carcinoma (especially in laryngeal cancer), which can significantly reduce the patient's distant metastasis rate and prolong overall survival (OS). However, the therapeutic effect of neoadjuvant therapy on head and neck squamous cell carcinoma has reached a bottleneck. In recent years, PD-1 inhibitors have achieved significant effects in the field of tumor therapy and have been approved for the treatment of various tumors including recurrent metastatic head and neck tumors. There are also several prospective clinical research attempting to combine ICB with targeted therapeutic drugs for neoadjuvant therapy of HNSCC. The efficacy and safety results show potential synergy between these drugs. Recent preclinical studies have shown that CDK4/6 inhibitors promote efficacy of PD-1/PD-L1 inhibitors through tumor antigen presentation enhancing, suppressed proliferation of regulatory T (Treg) cells, effector T- cell activation enhancing, and induction of T- cell memory. The previous study confirmed that CDK4/6 inhibitor combined with ICB can be administered safely in patients with recurrent or metastatic head and neck squamous cell carcinoma(HNSCC) and non-small cell lung carcinoma(NSCC). In summary, the investigators designed this study to explore the safety and efficacy of anti-PD1 immunotherapy, Camrelizumab, combined with CDK4/6 inhibitor, dalpiciclib, as a new neoadjuvant treatment regimen for patients with resectable HNSCC. It will also provide new ideas, strategies, and experimental evidence for the development of immunotherapy.
Interventions
DRUGCamrelizumab
Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery
Dalpiciclib will be given at a dose of 100 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.
Dalpiciclib will be given at a dose of 150 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.
Sponsors
West China Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or above. * Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following conditions: * were newly diagnosed and without distant metastasis; * were deemed surgically resectable evaluated by a head and neck surgeon; * were willing to undergo surgery. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Adequate organ and bone marrow function: absolute neutrophil count ≥ 1.5 × 10\^9/L, hemoglobin ≥ 80 g/L, platelets ≥ 80 × 10\^9/L;ALT, AST and ALP \< 2.5× upper limit of normal (ULN), total bilirubin ≤ 2×ULN;albumin≥ 2.8 g/dL；creatinine clearance ≥ 60 ml/min；INR≤ 1.5；APTT≤ 1.5×ULN * Written informed consent.
Exclusion criteria
* History of other malignancies (except for the history of malignant tumors that have been cured and have not recurred within 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, in situ cervical cancer, and gastrointestinal mucosal cancer, etc.） * Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease. * Any history of allergic disease, or a sever hypersensitivity reaction to drugs, or allergy to the study drug components. * Any of prior therapy with:anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； antitumor vaccine; any active vaccine against an infectious disease within 4 weeks prior to the first dose or planned during the study period; major surgery or serious trauma within 4 weeks before the first dose; toxicity from prior antitumor therapy has not recovered to ≤ CTCAE Version 5.0 ·Grade 1 or the level specified by the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of combination camrelizumab and dalpiciclib as assessed by number of participants who experience adverse events | Through the study completion, an average of 12 weeks | Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). |
| Feasibility of combination camrelizumab and dalpiciclib as assessed by number of participants who experience adverse events | Through the study completion, an average of 12 weeks | Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Through the study completion, an average of 12 weeks | Proportion of participants with measurable disease at baseline and have been re-evaluated after at least 1 cycle of therapy with observed reduction in tumor burden as defined by RECIST and iRECIST criteria after 2 doses of Proportion of participants with measurable disease at baseline and have been re-evaluated after at least 1 cycle of therapy with observed reduction in tumor burden as defined by RECIST and iRECIST criteria after 2 doses of nivolumab and ipilimumab. |
| Maximum Tolerated Dose (MTD) as determined by number of participants with dose limiting toxicities (DLT) | Through the study completion, an average of 12 weeks | Maximum tolerated dose will be determined by the maximum dose at which the least number of participants experience dose-limiting toxicity. The dose limiting toxicity is defined using the Common Terminology Criteria for Adverse Events (CTCAE). |
| Overall survival (OS) | Up to 2 years | Proportion of participants who achieve survival post treatment |
| Progression free survival(PFS) | Up to 2 years | Proportion of participants who achieve progression free survival post treatment |
| Major Pathologic Response | Time of surgery | Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells. |
Countries
China
Contacts
Primary ContactJin Zhou, MD.,PhD.
Backup ContactShangwei Sun
Outcome results
None listed