A Phase Ib Study With Pegylated Recombinant Human Endostatin in Advanced / Metastatic NSCLC or Other Solid Tumors

Study Overview
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Brief Summary
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The primary purpose of this study is to examine the safety, tolerability and pharmacokinetics of PEG-ENDO in combination with docetaxel in subjects previously treated or untreated (standard therapy is not suitable or without standard therapy) for advanced or metatatic non-small cell lung cancer (NSCLC) or other solid tumors.

Detailed Description
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This is a multicenter, open-label, dose-escalation study in subjects with advanced or metatatic non-small cell lung cancer (NSCLC) or other solid tumors.There will be five cohorts planning as following: cohort 1: PEG-ENDO 1 mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 2: PEG-ENDO 2mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 3: PEG-ENDO 4 mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 4: PEG-ENDO 6 mg/kg+Docetaxel75 mg/m2,once every 3 weeks at day 1 cohort 5: PEG-ENDO 8 mg/kg+Docetaxel75 mg/m2, once every 3 weeks at day 1 * Every 3 weeks as a treatment cycle. Subjects received only PEG-ENDO in the first cycle. For second cycle or the higher, they received a combination therapy of PEG-ENDO and docetaxel. Docetaxel was limited in 4 or 6 cycles。 The observation period of DLT was the 21 days after the first administration of PEG-ENDO. During the observation period of DLT (cycle 1), subjects only receive the corresponding dose of PEG-ENDO , for the second cycle and higher ,they will treated with the combination of PEG-ENDO and Docetaxel until disease progression (PD) or intolerance . Docetaxel was limited in 4 or 6 cycles。

Official Title
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A Phase Ⅰb Study Evaluating the Safety, Tolerability and Pharmacokinetics of Pegylated Recombinant Human Endostatin (PEG-ENDO) in Subjects With Advanced / Metastatic Non-small Cell Lung Cancer (NSCLC) or Other Solid Tumors

Conditions
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NSCLC, Solid Tumor

Intervention / Treatment
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* Drug: Pegylated Recombinant Human Endostatin（PEG-ENDO）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent. 18-70years old, male or female. Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer(NSCLC) or other solid tumor, previous treated with standard therapy , or standard therapy not suitabl ,or without standard therapy. At least one measurable disease according to RECIST v1.1. Life expectancy of at least 3 months. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1. Demonstrate adequate organ function - Exclusion Criteria: uncontrolled primary CNS tumors, brain metastases, or meningeal metastases. Evidence of a tumor that compresses or invades major blood vessels. History of hemoptysis (>1/2 teaspoon per event) or severe bleeding or evidence of bleeding disorders in the last 3 months. Clinically significant active cardiovascular disease within 6 months prior to planned start of PEG-ENDO. Prior treatment with anti-agiogenetic agent. Pregnant female patients; breastfeeding female patients. -

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-ENDO+Docetaxel<br>PEG-ENDO( 1 mg/kg or 2mg/kg or 4mg/kg or 6mg/kg or 8mg/kg）+Docetaxel 75 mg/m2，once every 3 weeks at day 1 | Drug: Pegylated Recombinant Human Endostatin（PEG-ENDO）<br>* PEG-ENDO 1 mg/kg or 2 mg/kg or 4 mg/kg or 6 mg/kg or 8 mg/kg+Docetaxel 75 mg/m2，once every 3 weeks at day 1<br>* Other names: Docetaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLT) | Incidence of Dose Limiting Toxicity | First 21days for dosing（Cycle1，each cycle is 21 days) | 
| Adverse Event(AE) | Incidence of Adverse Events | From the time the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment | 
| Serious Adverse Event(SAE) | Incidence of Serious Adverse Events | From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment | 
| Laborarory test abnormality | Incidence of clinically significant laboratory abnormalities | From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment | 
| Vital signs abnormality | Incidence of vital signs abnormalities | From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment | 
| Electrocardiogram(ECG) abnormality | Incidence of clinically significant ECG abnormalities | From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment | 
| Serum concentration | Serum concentration of PEG-ENDO | Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles. | 
| The maximum (or peak) serum ,Cmax | Cmax of PEG-ENDO following dose concentration. | Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles. | 
| AUC | The area under the plot of serum concentration of drug (not logarithm of the concentration) against time after drug administration. | Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles. | 
| other PK parameters | The other PK parameters (if applicable). | Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles. | 
| Maximum Tolerated Dose(MTD) | To determine the Maximum Tolerated Dose (MTD) of PEG-ENDO in subjects with Advanced / Metastatic NSCLC or Other Solid Tumors | First 21days for dosing（Cycle1，each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate(ORR) | ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | at least 12 weeks | 
| Duration of Response(DOR) | DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 | Estimated at 4 months after fist documented PD or CR | 
| Progression-free survival (PFS) | PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by by Investigator assessment in accordance to RECIST 1.1 | Estimated at 4 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pegylated recombinant human endostatin (PEG-ENDO)