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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04413227
• Other study ID #: SIM181202-PEGENDO-102
• Status: Recruiting
• Phase: Phase 1
• Start date: April 2, 2020
• Est. completion date: September 30, 2021

Study information

• Verified date: May 2020
• Source: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Contact: Huang Dingzhi, Ph.D
• Phone: 02223340123
• Email: dingzhih72[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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。

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 30, 2021
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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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Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Neoplasms
• NSCLC
• Solid Tumor

Intervention

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

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing	Beijing
China	Tianjin medical university cancer institute&hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Simcere Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLT)	Incidence of Dose Limiting Toxicity	First 21days for dosing(Cycle1,each cycle is 21 days)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	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
Secondary	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
Secondary	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.