Tislelizumab Combined With Chemotherapy Followed by Surgery Versus Up-front Surgery in Resectable Clinically Node-negative Head and Neck Squamous Cell Carcinoma

NCT06323369 | Recruiting Phase 2

• 1 other identifier: SYSKY-2023-1283-02
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective, randomized, open-label, multicenter Phase 2 trial designed to compare the efficacy and safety of Tislelizumab combined with chemotherapy followed by surgery versus up-front surgery in resectable clinically node-negative head and neck squamous cell carcinoma.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Disease-Free Survival(DFS )

  Time from randomization until recurrence of tumor or death from any cause

  3years

• Lymph node positivity rate

  Proportion of positive lymph nodes in resection specimens among total subjects

  Within 30 days after surgery

Secondary Outcomes (7)

• Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Adverse Events

  From time of first dose of study treatment until the end of follow-up (up to 5 years)

• Pathological complete response (pCR) rate

  Up to 30 days post-sugery

• Major Pathological Response (MPR) rate

  Up to 30 days post-sugery

• lymph node division

  Within 30 days after surgery

• Event-free Survival (EFS)

  3 years

Study Arms (2)

Neoadjuvant Tislelizumab + Chemotherapy (Arm A)

EXPERIMENTAL

Neoadjuvant therapy ( 3 cycles ) ： Cycle1、2、3（Cycle length: 21 days）：Tislelizumab(IV) , dose= 200mg, day=1; Cisplatin(IV) , dose=75 mg/m2, or Carboplatin(IV) , AUC=5, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Following surgical resection, lymph node positive participants receive 200 mg Tislelizumab Q3W plus chemoradiotherapy as adjuvant therapy. Lymph node negative participants receive 200 mg Tislelizumab Q3W as adjuvant therapy.

Drug: Tislelizumab（neoadjuvant）; Drug: Cisplatin （neoadjuvant）; Drug: Nab-paclitaxel （neoadjuvant）; Procedure: Surgical resection; Drug: Cisplatin（adjuvant）; Drug: Tislelizumab（adjuvant）; Radiation: Radiation; Drug: Carboplatin（neoadjuvant）; Drug: Carboplatin（adjuvant）

Up-front Surgery (Arm B)

ACTIVE COMPARATOR

Following surgical resection, lymph node positive participants receive chemoradiotherapy as adjuvant therapy. Lymph node negative participants receive follow-up.

Procedure: Surgical resection; Drug: Cisplatin（adjuvant）; Radiation: Radiation; Drug: Carboplatin（adjuvant）

Interventions

Tislelizumab（neoadjuvant） DRUG

Tislelizumab 200 mg administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Neoadjuvant Tislelizumab + Chemotherapy (Arm A)

Cisplatin （neoadjuvant） DRUG

Cisplatin 75 mg/m2 administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Neoadjuvant Tislelizumab + Chemotherapy (Arm A)

Nab-paclitaxel （neoadjuvant） DRUG

Nab-paclitaxel 260mg/m2 administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Neoadjuvant Tislelizumab + Chemotherapy (Arm A)

Surgical resection PROCEDURE

Standard of care

Neoadjuvant Tislelizumab + Chemotherapy (Arm A); Up-front Surgery (Arm B)

Cisplatin（adjuvant） DRUG

Cisplatin 100 mg/m2 administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Neoadjuvant Tislelizumab + Chemotherapy (Arm A); Up-front Surgery (Arm B)

Tislelizumab（adjuvant） DRUG

Tislelizumab 200 mg administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Neoadjuvant Tislelizumab + Chemotherapy (Arm A)

Radiation RADIATION

Recommended, standard of care

Neoadjuvant Tislelizumab + Chemotherapy (Arm A); Up-front Surgery (Arm B)

Carboplatin（neoadjuvant） DRUG

Cisplatin AUC=5 administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Neoadjuvant Tislelizumab + Chemotherapy (Arm A)

Carboplatin（adjuvant） DRUG

Cisplatin AUC=5 administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Neoadjuvant Tislelizumab + Chemotherapy (Arm A); Up-front Surgery (Arm B)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically confirmed diagnosis of HNSCC which is planned for treatment with curative intent including surgical resection: stage III/IVA.
• Greater than or equal to 18 and less than 80 years of age at time of study entry.
• ECOG performance status of 0 or 1. Measurable disease as per RECIST 1.1. Patients must have no prior exposure to immune-mediated therapy, including anti- cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1, anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines.
• Screening labs must meet the following criteria and must be obtained within 14 days prior to registration:
• Adequate hepatic and renal function as demonstrated by
• Serum creatinine \< 1.5 X ULN or CrCl \> 40mL/min (if using the Cockcroft-Gault formula below):
• Males: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum creatinine (mg/dL)） Females: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum creatinine (mg/dL))x 0.85 AST/ALT ≤ 3 x ULN Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Adequate bone marrow function as demonstrated by:
• Absolute Neutrophil Count \>1,500/µL Platelets \> 100 X 103/µL Hemoglobin \> 9.0 g/dL Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 21 days of study enrollment.
• Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; "women of reproductive potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
• Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year; men who are receiving the study medications will be instructed to adhere to contraception for 31 weeks after the last dose of study drugs; men who are azoospermic do not require contraception.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Subjects must agree to allow use of any pre-treatment tissue remaining after definitive diagnosis is made (ie, archival and or fresh tissue) for research purposes. In addition, subjects must consent to allow use of their residual post-operative tissue for research purposes.

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had another known invasive malignancy within the previous 5 years and/or has had surgery, chemotherapy, targeted small molecule therapy or radiation therapy within 5 years for a known malignancy prior to study day 0.
• If subject received major surgery for any other reason, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day -5. Inhaled or topical steroids, and adrenal replacement steroid \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Has an active autoimmune disease requiring systemic steroid treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids.
• Active, known or suspected autoimmune disease. Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger .
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• A history of allergic reaction attributed to compounds of similar chemical or biologic composition to the treatment or other agents used in the study.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the last dose of trial treatment.
• Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibodies).
• Has known active Hepatitis B or C. Known history of active TB (bacillus tuberculosis ).

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Medical Ethics Committee of Sun Yat-sen Memorial Hospital

Guangzhou, Yuexiu, 510120, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiation

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Physical Phenomena

Central Study Contacts

Bin Wei

CONTACT

18476425874; weib6@mail2.sysu.edu.cn

Qunxing Li

CONTACT

81332471; liqx73@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: March 21, 2024
• Study Start: March 25, 2024
• Primary Completion (Estimated): March 25, 2029
• Study Completion (Estimated): September 25, 2029
• Last Updated: May 17, 2024

Record last verified: 2024-05

Locations

CN (1)