A Study of Anti-VEGF Monoclonal Antibody hPV19 in Patients With Solid Tumors

NCT03503604 | Unknown Phase 1

• 1 other identifier: STW201701B
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

hPV19 is a monoclonal antibody (mAb) directed against vascular endothelial growth factor (VEGF). hPV19 binds to human VEGF with unique binding site on VEGF different from that of Bevacizumab(Avastin) and inhibits the binding of VEGF to it's receptors, VEGF-R1 and VEGF-R2. By preventing VEGF binding to its receptors, growth of tumor blood vessels are inhibited and tumor growth prevented or slowed. In this study we are investigating the tolerability, safety, pharmacokinetics and anti-tumor activity of hPV19 in combination with chemotherapy in patients with solid tumors. hPV19 will give to patients by intravenous(i.v.) infusion with a single and multiple doses.

Conditions

Solid Tumors

Keywords

mAb; VEGF; antibody; phase1

Outcome Measures

Primary Outcomes (2)

• Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period

  DLTs were adverse events (AEs) possibly related to study drug that met the National Cancer Institute's Common Terminology Criteria for AEs (NCI CTCAE, version 4.03) with any one of the following: 1. Grade 4 neutropenia ≥7 days; febrile neutropenia; grade 4 anemia; grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding; 2. ≥ grade 3 nonhematologic toxicity with the exception of nausea, vomiting, diarrhea, dehydration or electrolyte abnormalities that resolved to a lower grade with maximum supportive treatment within 3 days; 3. ≥Grade 3 hypertension that cannot resolved to a lower grade with supportive treatment within 2 weeks or uncontrolled hypertension; 4. Urine protein ≥3.5 grams/24 hours and cannot resolved to \< 1.0 grams/24 hours within 2 weeks; 5. Gastrointestinal perforation: symptoms, signs and imaging evidence of abdominal pain require surgical treatment; 6. Grade 3 or 4 arterial thromboembolism, including stroke and myocardial infarction;

  during the first 21 days

• Number of Participants With hPV19 Drug-Related Adverse Events or Serious Adverse Events

  Data are presented for the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade ≥3 TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to hPV19. Events related to chemotherapy were reported separately.

  Baseline to the last dose plus 28 days.

Secondary Outcomes (7)

• Number of Participants With Serum Anti-hPV19 Antibodies (Immunogenicity)

  before Single dose; Day 21 of 21-day DLT assessment period; Every 8 or 9 weeks after 21-day DLT assessment period.

• Maximum Concentration (Cmax) of hPV19

  Single dose(Cycle 1)：2h before administered; after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.

• Area Under the Curve (AUC) of hPV19

  Single dose(Cycle 1)：2h before administered, after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.

• Half Life (t1/2) of hPV19

  Single dose(Cycle 1)：2h before administered, after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.

• Clearance (CL) of hPV19

  Single dose(Cycle 1)：2h before administered, after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.

Study Arms (4)

group 1

EXPERIMENTAL

hPV19 mAb plus FOLFOX(5-Fluorouracil,Oxaliplatin,Leucovorin)

Biological: hPV19 mAb; Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

group 2

EXPERIMENTAL

hPV19 mAb plus paclitaxel/carboplatin

Biological: hPV19 mAb; Drug: Paclitaxel; Drug: Carboplatin

group 3

EXPERIMENTAL

hPV19 mAb plus gemcitabine/carboplatin

Biological: hPV19 mAb; Drug: Gemcitabine; Drug: Carboplatin

group 4

EXPERIMENTAL

hPV19 mAb plus FOLFIRI(5-Fluorouracil,Irinotecan, Leucovorin)

Biological: hPV19 mAb; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Irinotecan

Interventions

hPV19 mAb BIOLOGICAL

Intravenous (IV) infusions, 4 and 6 milligrams per kilogram (mg/kg) every 2 weeks

Also known as: anti-VEGF mAb

group 1; group 4

5-Fluorouracil DRUG

400 mg/m2 bolus followed by a 2400 mg/m2 continuous infusion, every 2 weeks

group 1; group 4

Oxaliplatin DRUG

IV Infusion, 85 milligrams per square meter (mg/m2) every 2 weeks

group 1

Leucovorin DRUG

IV infusion, 400 mg/m2 every 2 weeks

group 1; group 4

Paclitaxel DRUG

IV infusion, 175 mg/m2 every 3 weeks

group 2

Carboplatin DRUG

IV infusion, AUC=6 every 3 weeks

group 2

Gemcitabine DRUG

IV infusion, 1000 mg/m2 at day1 and day 8 every 3 weeks

group 3

Irinotecan DRUG

IV Infusion,180 milligrams per square meter (mg/m2) every 2 weeks

group 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed malignity
• Measurable disease
• Performance status 2 or less(ECOG)
• Life expectancy ≥3 months

You may not qualify if:

• hepatitis C virus (HCV), or HIV antibody positive
• Previously received anti-VEGF mAb or fusion-protein drugs within 28 days nearly
• Evidence of serious infection

Sponsors & Collaborators

• SuZhou Stainwei Biotech Inc.: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

MeSH Terms

Interventions

Fluorouracil; Oxaliplatin; Leucovorin; Paclitaxel; Carboplatin; Gemcitabine; Irinotecan

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Camptothecin; Alkaloids

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2018
• First Posted: April 20, 2018
• Study Start: May 1, 2018
• Primary Completion: January 1, 2019
• Study Completion: March 1, 2019
• Last Updated: April 20, 2018

Record last verified: 2018-04

Locations

CN (1)