Combining Toripalimab with Gemcitabine and Cisplatin for Treating Advanced Head and Neck Cancer

Phase Ib Clinical Study of Toripalimab Combined With Gemcitabine and Cisplatin Neoadjuvant Chemotherapy in Patients With Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

This study is testing if a new combination of treatments, including Toripalimab, Gemcitabine, and Cisplatin, can help people with advanced head and neck cancer before their surgery.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University (Academic / other)
• Drugs / interventions: prednisone, chemotherapy
• Locations: 1 site (Zhuhai, Guangdong)
• Trial ID: NCT04947241 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of combining the PD-1 inhibitor Toripalimab with Gemcitabine and Cisplatin in patients with untreated locally advanced head and neck squamous cell carcinoma (HNSCC). The study will initially observe six patients for 90 days to assess dose-limiting toxicity (DLT) before expanding to a larger population if safety criteria are met. The trial aims to evaluate the potential of neoadjuvant therapy to improve outcomes in patients scheduled for surgery. The approach is designed to address the high rates of local and distant failure associated with advanced HNSCC.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with untreated locally advanced HNSCC who are eligible for surgical intervention.

Not a fit: Patients with advanced HNSCC who have already received treatment or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and reduce the risk of recurrence in patients with locally advanced HNSCC.

How similar studies have performed: Other studies have shown promising results with similar immunochemotherapy approaches in treating advanced cancers, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. Untreated locally advanced head and neck squamous cell carcinoma confirmed by histology or cytology;
2. Patients who are recommended to perform surgery;
3. Patients between 18 and 70 years old;
4. ECOG: 0～2 points;
5. Estimated survival time ≥ 6 months;
6. At least one measurable lesion should be detected according to the RECIST 1.1;
7. The major organs meet the following standards (no blood components and cell growth factors are injected within 14 days):

   1. Hemoglobin HB≥90 g/L; neutrophil ANC≥1.5×109/L; platelet count PLT≥100×109/L;
   2. Serum albumin ≥28g/L;
   3. Total bilirubin TBIL≤1.5×upper limit of normal, alanine aminotransferase ALT, aspartate aminotransferase AST≤2.5×upper limit of normal; if there is liver metastasis, ALT and AST≤5×upper limit of normal;
   4. Serum creatinine ≤1.5×upper limit of normal, and creatinine clearance ≥50 mL/min;
   5. Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × upper limit of normal (for the use of stable doses of anticoagulant therapy such as low molecular weight heparin or warfarin, and INR in the anticoagulant expected treatment can be filtered within the scope);
   6. TSH≤ upper limit of normal; if abnormal, the T3 and T4 levels should be examined, and the T3 and T4 levels are normal.
8. Women of childbearing age should take contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the medication period and within 3 months after the medication; the serum or urine pregnancy test is negative within 7 days before the study is enrolled, And must be a non-lactating patient, and the male should agree to take contraceptive measures during the study period and within 3 months after the end of the study period;
9. The subjects voluntarily joined the study, signed an informed consent form, had good compliance, and cooperated with the follow-up.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Allergic to anti-PD-1 monoclonal antibody, gemcitabine, or cisplatin;
3. History of other malignant tumors in the past 5 years or at the same time, except for cured skin basal cell carcinoma, cervical carcinoma in situ, and thyroid papillary carcinoma;
4. Uncontrollable clinical symptoms or diseases of the heart, such as: (1) Heart failure, NYHA Ⅱ, III or IV (2) Unstable angina (3) Myocardial infarction occurred within 1 year (4) Supraventricular in clinical significance or Patients with ventricular arrhythmia requiring clinical intervention;
5. Have received any of the following treatments:

   1. Have received any research relevant drugs before enrolling in this research;
   2. Enrolled in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or intervention in a new clinical study follow-up;
   3. Patients who need to be given corticosteroids (more than 10 mg prednisone equivalent dose per day) or other immunosuppressive agents for systemic treatment within 2 weeks before giving medication for the first time, except for local inflammation and prevention of allergies, nausea and vomiting The case of corticosteroids. In the absence of active autoimmune diseases, inhaled or topical steroids and adrenal corticosteroids with a dose greater than 10 mg per day of prednisone curative dose are allowed to replace;
   4. Have been vaccinated with anti-tumor vaccine or have been vaccinated with live vaccine within 4 weeks before the first administration of study drug;
   5. Received major surgery or severe trauma within 4 weeks before using the study drug for the first time;
   6. The left ventricular ejection fraction of the heart is greater than or equal to 60%;
6. Severe infection (CTC AE greater than grade 2) occurred within 4 weeks before the first use of the study drug, such as severe pneumonia, bacteremia, infection comorbidities that require hospitalization, etc.; baseline chest imaging examinations suggest active lung inflammation , There are symptoms and signs of infection 2 weeks before the first use of the study drug or the need for oral or intravenous antibiotic treatment (excluding prophylactic use of antibiotics);
7. Have active autoimmune diseases, history of autoimmune diseases;
8. A history of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation and bone marrow transplantation;
9. Patients with active tuberculosis infection found through medical history or CT examination, or patients with a history of active tuberculosis infection within 1 year before enrollment, or patients with a history of active tuberculosis infection but without formal treatment 1 year before being checked;
10. The subject has active hepatitis (HBV DNA ≥ 2000IU/ml or 10,000 copies/ml), hepatitis C (hepatitis C antibody is positive, and HCV-RNA is higher than the lower limit of the analysis method);
11. History of psychotropic drug abuse, alcohol and drug abuse;
12. Symptomatic brain metastases (confirmed or suspected);
13. The patients who are reckoned as not suitable for inclusion.

Where this trial is running

Zhuhai, Guangdong

• Fifth Affilliated Hospital of Sun Yat-sen University — Zhuhai, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Zhigang Liu, M.D. — Fifth Affilliated Hospital of Sun Yat-sen University
• Study coordinator: Zhigang Liu, M.D.

Conditions Locally Advanced Head and Neck Squamous Cell Carcinoma; Neoadjuvant Therapy; Anti-PD-1 Monopoly Antibody; immunochemotherapy; head and neck squamous cell carcinoma