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

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

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.

Study Overview

• Status: Unknown
• Conditions: NSCLC; Solid Tumor
• Intervention / Treatment: Drug: Pegylated Recombinant Human Endostatin（PEG-ENDO）

Detailed Description

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。

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Huang Dingzhi, Ph.D; Phone Number: 3220 02223340123; Email: dingzhih72@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100005
      • Not yet recruiting
      • Beijing Hospital
      • Contact: Li Lin, Ph.D; Phone Number: 010-85136714; Email: lilin_51@163.com
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute＆Hospital
      • Contact: Huang Dingzhi, Ph.D; Phone Number: 3220 02223340123; Email: dingzhih72@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed and dated, written informed consent.
2. 18-70years old, male or female.
3. 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.
4. At least one measurable disease according to RECIST v1.1.
5. Life expectancy of at least 3 months.
6. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
7. Demonstrate adequate organ function -

Exclusion Criteria:

1. uncontrolled primary CNS tumors, brain metastases, or meningeal metastases.
2. Evidence of a tumor that compresses or invades major blood vessels.
3. History of hemoptysis (>1/2 teaspoon per event) or severe bleeding or evidence of bleeding disorders in the last 3 months.
4. Clinically significant active cardiovascular disease within 6 months prior to planned start of PEG-ENDO.
5. Prior treatment with anti-agiogenetic agent.

6. Pregnant female patients; breastfeeding female patients.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEG-ENDO+Docetaxel; 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）; 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; Other Names: Docetaxel

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Huang Dingzhi, Ph.D, Tianjin Medical University Cancer Institute & Hospital; Principal Investigator: Li Lin, Ph.D, Beijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2020
• Primary Completion (Anticipated): May 31, 2021
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: May 25, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 28, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: pegylated recombinant human endostatin (PEG-ENDO)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Docetaxel; Endostatins
• Other Study ID Numbers: SIM181202-PEGENDO-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No