A Study of TC(Docetaxel and Carboplatin) Regimen With or Without Nimotuzumab in Recurrent Metastatic Oral Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This prospective, single-center, randomized, controlled study will evaluate the efficacy and safety of TC Regimenwith or without nimotuzumab in recurrent metastatic oral squamous cell carcinoma. Treatment may continue as long as participants are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.

Official Title
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A Phase II, Prospective, Single-center, Randomized, Controlled Study of TC(Docetaxel and Carboplatin) Regimen With or Without Nimotuzumab in Recurrent Metastatic Oral Squamous Cell Carcinoma

Conditions
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Oral Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Nimotuzumab
* Drug: Docetaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteer to participate in clinical research; fully understand and know the research and sign informed consent. Age ≥18 years, and ≤75years , either sex. Eastern Collaborative Oncology Group Performance status (ECOG PS) 0 ,1 or 2. Patients with distant metastasis and/or recurrence of oral squamous cell carcinoma (including gingival cancer, tongue cancer, lip cancer, buccal cancer, oral cancer, etc) diagnosed by histopathology (according to the 8th edition of AJCC). Unable to perform local treatment (including radiotherapy and surgery). Have at least one measurable lesion as defined by RECIST 1.1. Normal hepatic function: total bilirubin≤1.5×normal upper limit (ULN); Alanine aminotransferase and Aspartate aminotransferase levels ≤2.5×ULN or ≤5×ULN if liver metastasis is present. Normal renal function ：Creatinine ≤1.5×ULN or calculated creatinine clearance ≥45 mL/min (using Cockcroft/Gault formula to calculate ). Normal hematological function：absolute neutrophil count ≥1.5×109/L, platelet count ≥70×109/L, hemoglobin≥80g/L [no blood transfusion or erythropoietin (EPO) within 7 days] Dependency]. Has a life expectancy of at ≥3 months. Exclusion Criteria: ECOG PS >2. Patients who received radiotherapy, chemotherapy, monoclonal antibody and oral EGFR-TKI therapy within three months. Patients who are receiving any other investigational agents within 30 days prior to entering the study. The tumor has metastasized to the brain and / or pia mater. History of other malignancies (except for cured cervical carcinoma in situ or skin basal cell carcinoma and other malignancies that have been cured for more than 5 years). Accompanied by other serious diseases, including but not limited to: Uncontrollable congestive heart failure (NYHA grade Ⅲ or Ⅳ), unstable angina, poorly controlled arrhythmia, uncontrolled moderate or above hypertension (SBP > 160mmhg or DBP > 100mmhg) ; Severe active infection; Uncontrollable diabetes (refers to the high fluctuation of blood glucose, the impact on patients' life and the frequent occurrence of hypotension despite the standard insulin treatment and frequent blood glucose monitoring) ; Mental illness affecting informed consent and / or program compliance. Those who are allergic to the drug or its components used in the program. Pregnancy (confirmed by hCG test in blood or urine) or lactating women, or childbearing age subjects are unwilling or unable to take effective contraceptive measures (applicable to both male and female subjects) until at least 6 months after the last trial treatment. Those who are not considered suitable for the study by the researchers. Unwilling to participate in this study or unable to sign informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimotuzumab plus TC Regimen chemotherapy<br>Nimotuzumab (200 mg) plus TC Regimen chemotherapy every 3 weeks | Drug: Nimotuzumab<br>* Nimotuzumab will be administered intravenously at a fixed dose of 200 milligrams (mg) on Day 1 of each 21-day cycle.<br>Drug: Docetaxel<br>* Docetaxel 75 milligrams per square meter (mg/m^2) will be administered intravenously on Day 1 of each 21-day cycle.<br>Drug: Carboplatin<br>* Carboplatin AUC 5 will be administered intravenously on Day 1 of each 21-day cycle.<br>|
| Active Comparator: TC Regimen chemotherapy<br>TC Regimen chemotherapy every 3 weeks | Drug: Docetaxel<br>* Docetaxel 75 milligrams per square meter (mg/m^2) will be administered intravenously on Day 1 of each 21-day cycle.<br>Drug: Carboplatin<br>* Carboplatin AUC 5 will be administered intravenously on Day 1 of each 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare Progression Free Survival (PFS) between Nimotuzumab + TC Regimen chemotherapy and TC Regimen chemotherapy using RECIST 1.1. | PFS was defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1. | approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare objective response rate between Nimotuzumab + TC Regimen and TC Regimen chemotherapy. | ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria. | approximately 24 months | 
| Compare Overall Survival (OS) between Nimotuzumab + TC Regimen chemotherapy and TC Regimen chemotherapy | To compare the efficacy of the combination of Nimotuzumab plus TC Regimen chemotherapy versus TC Regimen chemotherapy in terms of overall survival (OS) in patients with recurrent metastatic oral squamous cell carcinoma. Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive. | approximately 24 months | 
| Compare Disease Control Rate (DCR) between Nimotuzumab + TC Regimen and TC Regimen chemotherapy. | DCR was defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD). | approximately 24 months | 
| Number of Participants who Experience Treatment Related Adverse Events (AEs). | All Adverse Events and Serious Adverse events will be collected and collated according to grade and frequency. AEs graded using CTCAE (Version 4.0) criteria. | approximately 24 months |