Clinical trial NCT04413227: A Phase Ib Study With Pegylated Recombinant Human Endostatin in Advanced / Metastatic NSCLC or Other Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: NSCLC
Solid Tumor
Keywords: pegylated recombinant human endostatin (PEG-ENDO)
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-06-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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。

Eligibility criteria: 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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Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: First 21days for dosing（Cycle1，each cycle is 21 days)
measure: Adverse Event(AE)
timeFrame: From the time the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
measure: Serious Adverse Event(SAE)
timeFrame: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
measure: Laborarory test abnormality
timeFrame: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
measure: Vital signs abnormality
timeFrame: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
measure: Electrocardiogram(ECG) abnormality
timeFrame: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
measure: Serum concentration
timeFrame: 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.
measure: The maximum (or peak) serum ,Cmax
timeFrame: 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.
measure: AUC
timeFrame: 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.
measure: other PK parameters
timeFrame: 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.
measure: Maximum Tolerated Dose(MTD)
timeFrame: First 21days for dosing（Cycle1，each cycle is 21 days)
Secondary outcomes:
measure: Overall Response Rate(ORR)
timeFrame: at least 12 weeks
measure: Duration of Response(DOR)
timeFrame: Estimated at 4 months after fist documented PD or CR
measure: Progression-free survival (PFS)
timeFrame: Estimated at 4 months.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Tianjin
country: China
facility: Tianjin medical university cancer institute&hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Huang Dingzhi, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Hospital
name: Li Lin, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: