PLD Combined With Cisplatin in the Treatment of Advanced Poorly Differentiated Thyroid Carcinoma

Study Overview
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Brief Summary
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This is a prospective, multicenter, open label Phase II Clinical Trial. 30 advanced poorly differentiated thyroid carcinoma patients who were histopathologically confirmed inoperable were enrolled in this study.

Detailed Description
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Subjects will receive the treatment regimen as follow: intravenous infusion of liposomal doxorubicin 35 mg/m2, d1; cisplatin 75 mg/m2, drip, total dose should be carried out on d1-3; once every 21days, for 6 cycles. Stop the treatment if the patients have progressed or intolerated to the toxicity. The primary endpoint is disease control rate(DCR), the secondary endpoint is overall survival (OS), progression-free survival (PFS), safety and quality of life assessment(QoL).

Official Title
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A Prospective, Multicenter, Open Label Phase Ⅱ Clinical Trial of Doxorubicin Hydrochloride Liposome Injection Combined With Cisplatin in the Treatment of Advanced Poorly Differentiated Thyroid Carcinoma

Conditions
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Poorly Differentiated Thyroid Carcinoma

Intervention / Treatment
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* Drug: PLD
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteer to participate and sign the informed consent form; Age :18-70 years old; Histopathologically confirmed inoperable advanced poorly differentiated thyroid carcinoma; Previously received surgery, I131 treatment, radiotherapy, chemotherapy patients can be enrolled； At least one measurable lesion according to the solid tumor efficacy evaluation criteria (RECIST 1.1); Expected survival time ≥ 3 months; Karnofsky score ≥70; Blood test：ANC ≥1.5×109/L； PLT ≥75×109/L；Hb ≥90g/L; Liver function:Serum bilirubin (SB) level:≤ normal upper limit（ULN）2 times; aspartate aminotransferase(AST) and alanine aminotransferase(ALT) ≤ ULN 2.5times; or ≤ ULN 5times if Liver metastases are present; Renal function: Serum creatinine ≤ ULN 1.5times; LVEF ≥ 50%; No serious complications such as active digestive tract hemorrhage, perforation, jaundice, gastrointestinal obstruction, noncancerous fever > 38℃; Subjects are well-behaved, able to undergo the follow-up efficacy and adverse reactions according to the program requirements. Exclusion Criteria: Active or uncontrolled severe infection (≥CTCAE grade 2 infection)； Previously received anthracycline-based regimen: the cumulative dose of doxorubicin at or above 500 mg / m2 or the cumulative dose of epirubicin reached or exceeded 800 mg / m2; The New York Heart Association (NYHA) graded class II or above heart disease patients previously or at present; Patients with CNS disorders or CNS metastases; Allergic to chemotherapeutic drugs or their excipients or intolerant patients; Received any other test drug treatment within 30 days of the first chemotherapy administration; Pregnant or lactating women; Arterial/venous thrombosis occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis, and pulmonary embolism; History of aneurysm; Neurological disorders with a history of epilepsy or ataxia require treatment; A history of drug abuse and incapable of abstinence or mental disorder; A history of peripheral neuropathy and the muscle strength is below level 3; Suffering from other diseases and complications of hand-foot syndrome; Researchers think it is not suitable for enrolling.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: PLD plus Cisplatin<br>liposomal doxorubicin(PLD) 35 mg/m2,iv,d1, plus cisplatin 75 mg/m2,drip,d1-3, once every 21days, for 6 cycles, to progression or intolerance. | Drug: PLD<br>* intravenous infusion of liposomal doxorubicin 35 mg/m2, d1,once every 21days, for 6 cycles.<br>* Other names: duomeisu;Drug: Cisplatin<br>* cisplatin 75 mg/m2, drip, total dose should be carried out on d1-3; once every 21days, for 6 cycles.<br>* Other names: shunbo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease control rate(DCR) | the rate of CR,PR and SD | disease control rate will be evaluated every 2 cycles (each cycle is 21 days) from date of administration of drugs until the date of first documented progression，up to 18 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | overall survival | From date of randomization until the date of death from any cause,assessed up to 18 months. | 
| PFS | progression-free survival | From date of randomization until the date of first documented disease progression or date of death from any case,whichever came first,assessed up to 18 months. | 
| Incidence of adverse events assessed by number and severity of adverse event in the treatment. | Evaluate the adverse reaction rate of drugs assessed by number and severity of adverse events in the treatment of advanced thyroid poorly differentiated carcinoma. | A summary of adverse events of each cycle,from date of administration of drugs until 30 days after the last chemotherapy or progression,whichever came first,assessed up to 18 months. | 
| quality of life assessment | Evaluate the QoL according to Functional Assessment of Cancer Therapy. | It will be assessed before the administration of drugs at each first day of the chemotherapy cycle,up to 6 cycles,each cycle is 21 days. |