Preoperative Tislelizumab -Cetuximab - Chemotherapy Followed by Salvage Surgery and Adjuvant Tislelizumab -Cetuximab for Resectable, Locally Recurrent Oral and Oropharyngeal Squamous Cell Carcinoma

Launched by SHANGHAI ZHONGSHAN HOSPITAL · Dec 8, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with locally recurrent oral and oropharyngeal squamous cell carcinoma, which is a type of cancer affecting the mouth and throat. The trial will test a combination of medications, including immunotherapy (Tislelizumab), targeted therapy (Cetuximab), and chemotherapy (Cisplatin and Nab-paclitaxel), given before surgery to help shrink the tumors. After surgery, patients will continue receiving Tislelizumab and Cetuximab for about six months. The goal is to see how effective and safe this treatment strategy is for patients who may still have cancer after initial treatment.

To be eligible for this trial, participants should be between 18 and 75 years old, have confirmed recurrent oral or oropharyngeal squamous cell carcinoma, and have had at least 16 weeks since their last treatment before the cancer came back. They must also be healthy enough to undergo surgery and have at least one measurable tumor. Participants can expect to receive careful monitoring and support throughout the study, and it's important to note that women who can become pregnant and men must agree to use birth control during the trial. This study is not yet recruiting participants, but it aims to offer new hope for those facing this challenging diagnosis.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Participants must have histologically or cytologically confirmed locoregionally recurrent oral/oropharyngeal squamous cell carcinoma (including tongue, lips, gums, cheeks, floor of mouth, hard palate, soft palate, posterior molar area, lateral pharyngeal wall, posterior pharyngeal wall, tonsils).
• • 2. Participants must have documented time of ≥ 16 weeks from completion of prior curative intent treatment for OSCC (surgery and/or radiation therapy with/without platinum chemotherapy or cetuximab targeted therapy) to diagnosis of local or locoregional recurrence.
• • 3. Age ranges from 18 to 75 years old
• • 4. ECOG performance status 0 or 1.
• • 5. Expected survival ≥ 12 weeks.
• • 6. The participants are clinically evaluated to be eligible for salvage surgery and must be intended to undergo salvage surgery.
• • 7. There must be at least one clinically assessable lesion according to the RECIST V1.1 criteria prior to treatment.
• • 8. The participants may have any human papillomavirus (HPV) status of the tumor. Patients with oropharyngeal cancer need to undergo HPV testing, including p16 immunohistochemistry and/or confirmatory HPV polymerase chain reaction (PCR) or in situ hybridization (ISH) testing.
• • 9. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and continue contraception for 12 months after the end of treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• • 10. Participants must have adequate organ and marrow function as defined below: The function of important organs meets the following requirements: (1) normal bone marrow reserve function, white blood cell (WBC) ≥ 3.0 × 10 \^ 9/L; Neutrophil count (NEUT) ≥ 1.5 × 10 \^ 9/L, platelet count (PLT) ≥ 100 × 10 \^ 9/L, hemoglobin (Hb) ≥ 90 g/L; (2) Normal renal function or serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥ 50 ml/min (Cockcroft Gault formula); (3) Normal liver function or total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); AST or ALT levels ≤ 3 times the upper limit of normal (ULN); (4) Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously. If FT3 and FT4 levels are normal, they can be included in the group).
• • 11. The participants voluntarily joined this study, signed an informed consent form, had good compliance, and cooperated with follow-up.
• Exclusion Criteria:
• • 1. Has known distant metastasis of the disease.
• • 2. Has received chemotherapy or radiotherapy for curative treatment of oral/oropharyngeal squamous cell carcinoma within the 16 weeks prior to enrollment in the study.
• • 3. Has received therapy treatment with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, or anti-CTLA-4 antibody (or any other antibody acting on T cell co stimulatory or checkpoint pathways).
• • 4. Has received live or attenuated vaccines within 30 days prior to the first dose of Tislelizumab, inactivated vaccines are allowed.
• • 5. Has received immunosuppressive drugs within 14 days prior to the first dose of study drug, nasal and inhaled corticosteroids or physiological doses of systemic corticosteroids (i.e. not exceeding 10 mg/day of prednisolone or other corticosteroids of equivalent physiological doses) are allowed.
• • 6. Has an active infection that requires systematic treatment; Has a history of non -infectious pneumonia/interstitial lung disease requiring steroid treatment, or current pneumonia/interstitial lung disease; Has a known history of hepatitis B (defined as positive for hepatitis B surface antigen \[HBsAg\]) or known history of active hepatitis C virus (defined as detection of HCV RNA \[qualitative\]) infection; Has a known history of human immunodeficiency virus (HIV) infection.
• • 7. Has received allogeneic tissue/solid organ transplantation.
• • 8. Has not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 2) with the exception of alopecia.
• • 9. Has obvious cardiovascular abnormalities (such as myocardial infarction, superior vena cava syndrome, and heart disease grade 2 or above diagnosed according to the New York Heart Association (NYHA) classification criteria within 3 months prior to the enrollment)。
• • 10. Has severe clinical infection (\>NCI-CTCAE 5.0 Level 2 infection);
• • 11. Has uncontrollable hypertension (systolic blood pressure\>150mmHg and/or diastolic blood pressure\>90mmHg after treatment with antihypertensive drugs) or clinically significant cardiovascular diseases - such as cerebrovascular accidents (≤ 6 months before enrollment), myocardial infarction (≤ 6 months before enrollment), unstable angina, congestive heart failure classified as Grade II or above by the New York Heart Association (NYHA), or severe arrhythmias that cannot be controlled with medication or have potential impact on experimental treatment.
• • 12. Pregnant women are not allowed to participate. Breast-feeding women who participate in this study should stop breast-feeding.
• • 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• • 14. Has participated in other clinical studies within 30 days prior to enrollment.
• • 15. Other situations that researchers consider unsuitable for participation in the study.