Weekly Docetaxel Plus Cisplatin as First-line Chemotherapy in Metastatic Salivary Gland Cancer Patients : a Multicenter Phase II Study

Study Overview
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Brief Summary
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Cisplatin plus weekly docetaxel as first-line chemotherapy in metastatic salivary gland cancer patients : a multicenter phase II study

Detailed Description
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Preclinically, paclitaxel and docetaxel have demonstrated activity against salivary gland cancers1. Phase II trial of single-agent paclitaxel2, conducted by Eastern Cooperative Oncology Group in 45 patients with advanced SGC. Eight partial responses were observed among the 31 patients with mucoepidermoid carcinoma (MEC) or adenocarcinoma, but no responses were identified in the 14 patients with ACC. Based on its impressive anti-tumor activity in patients with head and neck cancer, especially in squamous cell carcinoma, Ragusa et al.3 evaluated the activity of docetaxel in 4 patients with high grade MEC of the major salivary glands. The treatment was well tolerated, and there was complete response in two and partial response in the other two patients. However, myelosuppression is one of the serious concerns with every 3 week schedule of docetaxel administration, especially in older patients. Alternatively, a weekly dosing of docetaxel has been reported to reduce toxicity and Investigator previously reported weekly docetaxel and cisplatin chemotherapy in recurrent or metastatic nasopharyngeal cancer demonstrated high response rate with modest toxicities4. So Investigator planned this phase II study to evaluate the efficacy and safety of cisplatin plus weekly docetaxel in patients with metastatic salivary gland cancer.

Official Title
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Weekly Docetaxel Plus Cisplatin as First-line Chemotherapy in Metastatic Salivary Gland Cancer Patients : a Multicenter Phase II Study

Conditions
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Salivary Gland Cancer

Intervention / Treatment
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* Drug: docetaxel plus Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed salivary gland cancer with one of the following histologic subtypes : mucoepidermoid, adenocarcinoma/ductal carcinoma or adenoid cystic carcinoma Only progressive disease in case of ACC Progressive disease is defined as one of the following occurring within 6 months of study entry (i) at least a 20% increase in radiologically or clinically measurable disease, (ii) appearance of new lesions or (iii) deterioration in clinical status stage IV or recurrent cancer which is incurable with surgery or radiotherapy age ≥ 20 years ECOG performance status 0-1 ⑥ At least one measurable tumor lesion according to RECIST 1.1 Expected survival for approximately 12 weeks or longer ⑧ No prior systemic chemotherapy (Patients who received adjuvant chemotherapy or chemoradiotherapy completed more than 6 months before will be eligible) At least 4 weeks later after major surgery or radiotherapy ⑩ Organ function as evidence by the following; WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3, ANC ≥ 1,500 cells/mm3, Hemoglobin ≥ 10 g/dL (transfusion allowed), Platelet count ≥ 100,000 plts/mm3; Total bilirubin ≤ 1.5 ULN AST/ALT ≤ 2.5 ULN, (if liver metastases: AST, ALT ≤5.0 x ULN); Creatinine clearance 50 mL/min or serum creatinine ≤ 1.5 x UNL ⑪ Written informed consent Exclusion Criteria: Severe or unstable cardiac disease, including (for example) coronary artery disease requiring increased doses of anti-anginal medication and/or coronary angioplasty (including stent placement) within the preceding 24 months (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias) Uncontrolled systemic illness such as DM, hypertension, hypothyroidism and infection Pregnant and nursing women (women of reproductive potential have to agree to use an effective contraceptive method) ④ Symptomatic CNS malignancy (history of completely resected or irradiated brain metastases by WBRT or stereotactic radiosurgery allowed) ⑤ Patients with alcohol abuse

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin plus docetaxel<br>D1, D8 Docetaxel 35 mg/m2 + D5W 100mL MIV over 1hr D1 Cisplatin 70mg/m2 + NS 150mL MIV over 1hr every 3 weeks Treatment will be continued until disease progression or unacceptable toxic effects. | Drug: docetaxel plus Cisplatin<br>* D1, D8 Docetaxel 35 mg/m2 + D5W 100mL MIV over 1hr D1 Cisplatin 70mg/m2 + NS 150mL MIV over 1hr every 3 weeks Treatment will be continued until disease progression or unacceptable toxic effects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | To evaluate the effectiveness of regimen. The overall response rate will be measured by RECIST v1.1. | Up to 30months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overal survival defined by date of all-cause mortality from date of IP administration will be calculated. | The time until defineded by date of all-cause mortality from date of IP administration. Up to 30 months. | 
| progression-free survival (PFS) | It is measure of the period of survival without disease progression. | The time until the date of either disease progression or the all cause mortality from the date of IP administration. Up to 30months. | 
| Adeverse event(AE) | Adverse event will be evaluate using CTCAE V.4.0 | from the date of informed consent signature to 21days after last drug administration. |