Trial Title:
A Phase II Study of Neoadjuvant Immunotherapy in Combination With Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma
NCT ID:
NCT06444009
Condition:
Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Conditions: Keywords:
Locally advanced head and neck squamous cell carcinoma
Neoadjuvant therapy
Immunotherapy
AK112
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
A Randomized, Controlled, Phase II Study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ivonescimab combined with TP
Description:
Both interventions all drugs intravenous infusion, D1, once every 3 weeks, a total of 3
cycles.
Arm group label:
Ivonescimab in combination with Nab-paclitaxel + Cisplatin
Other name:
ITP
Intervention type:
Drug
Intervention name:
Cadonilimab combined with TP
Description:
Both interventions all drugs intravenous infusion, D1, once every 3 weeks, a total of 3
cycles.
Arm group label:
Cadonilimab in combination with Nab-paclitaxel + Cisplatin
Other name:
CTP
Intervention type:
Drug
Intervention name:
Penpulimab combined with TP
Description:
Both interventions all drugs intravenous infusion, D1, once every 3 weeks, a total of 3
cycles.
Arm group label:
Penpulimab in combination with Nab-paclitaxel + Cisplatin
Other name:
PTP
Summary:
A Randomized, Phase II Study of ivonescimab or cadonilimab or penpulimab in Combination
With Cisplatin and Nab-paclitaxel in Patients With III-IVB (according to the 8th edition
of UICC/AJCC staging) locally advanced head and neck squamous cell carcinoma (HNSCC)
eligible for resection. This proposed study will evaluate the efficacy and safety of
preoperative administration of ivonescimab or cadonilimab or penpulimab combined with
chemotherapy in HNSCC who are eligible for resection.
Detailed description:
In this study, eligible patients will be randomized in a 1:1:1 ratio to either the
ivonescimab combined with chemotherapy treatment group (Cohort 1), or the cadonilimab
combined with chemotherapy treatment group (Cohort 2), or the penpulimab combined with
chemotherapy treatment group (Cohort 3). Pathological response rate will be the primary
outcome measures. Adverse events will also be recorded.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Males and females； Age：18 to 75 years.
2. Histologically or cytologically confirmed head and neck squamous cell carcinoma
(HNSCC).
3. Patients with resectable locally advanced head and neck squamous cell carcinoma
(LA-HNSCC), classified as stage III-IVB according to the 8th edition of UICC/AJCC
staging.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. No prior treatment for the cancer.
6. Intention to undergo curative treatment.
7. Patients with normal organ function and suitable for immunotherapy combined with
chemotherapy and surgery:
Adequate hematologic function (total white blood cell count ≥ 3.0×10^9/L, absolute
lymphocyte count ≥ 0.8×10^9/L, absolute neutrophil count ≥ 1.5×10^9/L, platelets ≥
100×10^9/L, hemoglobin ≥ 90g/L); Adequate hepatic function (bilirubin level ≤ 2
times the upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels ≤ 2.5 times ULN); Adequate renal function (serum
creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 60 mL/min
(Cockcroft-Gault formula), urine protein <2+ on dipstick or <1g in a 24-hour urine
collection); Good cardiac function, i.e., normal or clinically insignificant
abnormalities on electrocardiogram (ECG), echocardiogram showing a left ventricular
ejection fraction (LVEF) ≥50%; Adequate coagulation function: International
Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times ULN; participants on
anticoagulation treatment are eligible if the PT is within the therapeutic range of
the anticoagulant;
8. Blood pressure well controlled (defined as systolic blood pressure ≤ 150 mmHg and
diastolic blood pressure ≤ 90 mmHg) with or without antihypertensive medication, and
no change in antihypertensive treatment within 1 week before the first dose of study
medication.
9. Patients with HBV infection capable of having detectable HBV DNA levels (≥10IU/mL or
above the limit of quantitation) (manifested as positive for hepatitis B surface
antigen (HbsAg) and/or hepatitis B core antibody (anti-HBc)) must receive antiviral
therapy according to clinical practice at the site before randomization to ensure
adequate viral suppression. Patients must maintain antiviral therapy during the
study and for 6 months after the last dose of study treatment. Patients who are
anti-HBc positive but do not have detectable HBV DNA (<10IU/mL or below the limit of
quantitation) are not required to receive antiviral therapy unless their HBV DNA
levels exceed 10IU/mL or the limit of quantitation during treatment.
10. Women of childbearing potential (15-49 years old) must have a negative pregnancy
test within 7 days before starting treatment; patients of childbearing potential
must agree to use effective contraception to ensure they do not become pregnant
during the study period and for 3 months after stopping treatment.
11. Participants voluntarily join the study, sign an informed consent form, have good
compliance, and cooperate with follow-up.
Exclusion Criteria:
1. Patients who have received any form of anti-tumor treatment previously.
2. Patients with allergic constitution and congenital immune deficiencies.
3. Patients who have undergone organ transplantation.
4. Patients with a history of severe bleeding tendencies or coagulation dysfunction;
those who have had clinically significant bleeding symptoms within 1 month prior to
the study treatment, including but not limited to gastrointestinal bleeding,
hemoptysis; those who have received prolonged anticoagulation treatment within 10
days prior to the study treatment.
5. Patients who have experienced arteriovenous thrombotic events within 6 months before
the study treatment, such as cerebrovascular accidents (including transient ischemic
attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and
pulmonary embolism.
6. Patients with active autoimmune diseases or inflammatory diseases, or a history
thereof, including inflammatory bowel disease (e.g., colitis or Crohn's disease),
diverticulitis (excluding diverticulosis), systemic lupus erythematosus, sarcoidosis
or Wegener's granulomatosis (e.g., granulomatosis with polyangiitis, Graves'
disease, rheumatoid arthritis, hypophysitis, and uveitis). Exceptions to this
criterion include patients with vitiligo or alopecia; patients with stable
hypothyroidism after hormone replacement therapy (e.g., following Hashimoto's
thyroiditis); patients with any chronic skin disease not requiring systemic
treatment; inclusion of patients without active disease in the last 5 years is
allowed only after consultation with the study physician.
7. Patients with active infections, including tuberculosis or human immunodeficiency
virus (HIV 1/2 antibody positive).
8. Patients with uncontrollable complications, including but not limited to: persistent
or active infections receiving study treatment (except HBV or HCV), symptomatic
congestive heart failure, uncontrolled diabetes, uncontrolled hypertension, unstable
angina, uncontrolled arrhythmias, active interstitial lung disease, severe chronic
gastrointestinal disease with diarrhea, or any psychiatric/social situations that
might limit compliance with study requirements, significantly increase the risk of
adverse events (AE), or impair the ability of the patient to give written informed
consent.
9. Pregnant or breastfeeding women.
10. Patients who do not agree to use effective contraception during the treatment period
and for 3 months thereafter.
11. Patients participating in other clinical studies simultaneously.
12. Patients who are critically ill and unable to complete the investigation.
13. Patients with a history of other primary malignant tumors, except for the following:
Malignant tumors treated with curative intent and no known active disease for ≥5
years prior to study treatment and with a low risk of relapse; adequately treated
non-melanoma skin cancer or in-situ melanoma without evidence of disease; adequately
treated carcinoma in situ without evidence of disease.
14. Patients with a history of psychiatric illness (e.g., schizophrenia, mania, anxiety
disorder, depression, phobia) or diagnosed with a psychiatric disease at the time of
enrollment or their spouses.
15. Patients or their spouses with communication barriers due to confusion, aphasia,
intellectual disability, or other reasons that prevent normal responses.
16. Patients with other malignant neoplastic diseases.
17. Patients whom the researcher considers unsuitable for inclusion or whose
participation might affect their ability to participate or complete the study for
other reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
June 1, 2024
Completion date:
December 1, 2027
Lead sponsor:
Agency:
Lei Liu
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/NCT06444009
