Trial Title:
Neoadjuvant Camrelizumab With Dalpiciclib for Resectable Head and Neck Squamous Cell Carcinomas
NCT ID:
NCT06109207
Condition:
Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Conditions: Keywords:
Head and Neck Squamous Cell Carcinoma
Neoadjuvant therapy
Immunotherapy
CDK4/6 inhibitor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Camrelizumab
Description:
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
Arm group label:
Camrelizumab+Dalpiciclib(100mg) 3 patients
Arm group label:
Camrelizumab+Dalpiciclib(150mg) 3 patients
Intervention type:
Drug
Intervention name:
Dalpiciclib 100mg
Description:
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.
Arm group label:
Camrelizumab+Dalpiciclib(100mg) 3 patients
Intervention type:
Drug
Intervention name:
Dalpiciclib 150mg
Description:
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.
Arm group label:
Camrelizumab+Dalpiciclib(150mg) 3 patients
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.
Criteria for eligibility:
Criteria:
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/exclusion criteria.
- With serious medical diseases, such as grade II and above cardiac dysfunction (NYHA
criteria), ischemic heart disease, supraventricular or ventricular arrhythmia,
poorly controlled diabetes mellitus, poorly controlled hypertension,
echocardiographic ejection fraction < 50%, etc.
- With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary
tuberculosis, or history of pulmonary tuberculosis infection that were not
controlled by treatment.
- With hyperthyroidism, or organic thyroid disease.
- With active infection, or unexplained fever during the screening period or 48 hours
before the first dose.
- With active hepatitis B or C, or known history of positive HIV test, or acquired
immunodeficiency syndrome.
- History of a clear neurological or psychiatric disorder.
- History of drug abuse or alcohol abuse.
- Women who are pregnant or breastfeeding, or have a reproductive plan from the
screening period to 3 months after the end of the study, or have sex without
contraceptive measures, or are unwilling to take appropriate contraceptive measures.
- Received any investigational drug within 4 weeks prior to the first dose, or
concurrently enrolled in another clinical trial.
- Any other factors that are not suitable for inclusion in this study judged by
investigators.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
West China Hospital, Sichuan University
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Jin Zhou, MD.,PhD.
Phone:
+8613880626596
Email:
zhoujin096@scu.edu.cn
Contact backup:
Last name:
Shangwei Sun
Phone:
+8615291996883
Email:
sunshangwei@stu.scu.edu.cn
Start date:
October 31, 2023
Completion date:
October 31, 2025
Lead sponsor:
Agency:
West China Hospital
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06109207
