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

Solid Tumors Clinical Trial

Official title:

A Phase Ib Study of hPV19, a Novel Humanized Monoclonal Antibody Against Vascular Endothelial Growth Factor (VEGF),in Combination With Chemotherapy in Patients With Advanced Solid Tumors Refractory to Standard Therapy.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03503604
• Other study ID #: STW201701B
• Status: Not yet recruiting
• Phase: Phase 1
• First received: March 20, 2018
• Last updated: April 18, 2018
• Start date: May 1, 2018
• Est. completion date: March 1, 2019

Study information

• Verified date: April 2018
• Source: SuZhou Stainwei Biotech Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: March 1, 2019
• Est. primary completion date: January 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Confirmed malignity

• Measurable disease

• Performance status 2 or less(ECOG)

• Life expectancy =3 months

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Biological:
• hPV19 mAb
Intravenous (IV) infusions, 4 and 6 milligrams per kilogram (mg/kg) every 2 weeks
• hPV19 mAb
Intravenous (IV) infusions, 6 milligrams per kilogram (mg/kg) every 3 weeks

Drug:
• 5-Fluorouracil
400 mg/m2 bolus followed by a 2400 mg/m2 continuous infusion, every 2 weeks
• Oxaliplatin
IV Infusion, 85 milligrams per square meter (mg/m2) every 2 weeks
• Leucovorin
IV infusion, 400 mg/m2 every 2 weeks
• Paclitaxel
IV infusion, 175 mg/m2 every 3 weeks
• Carboplatin
IV infusion, AUC=6 every 3 weeks
• Gemcitabine
IV infusion, 1000 mg/m2 at day1 and day 8 every 3 weeks
• Carboplatin
IV infusion, AUC=4 every 3 weeks
• Irinotecan
IV Infusion,180 milligrams per square meter (mg/m2) every 2 weeks

Locations

Country	Name	City	State
China	Shanghai East Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
SuZhou Stainwei Biotech Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: Grade 4 neutropenia =7 days; febrile neutropenia; grade 4 anemia; grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding; = 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; =Grade 3 hypertension that cannot resolved to a lower grade with supportive treatment within 2 weeks or uncontrolled hypertension; Urine protein =3.5 grams/24 hours and cannot resolved to < 1.0 grams/24 hours within 2 weeks; Gastrointestinal perforation: symptoms, signs and imaging evidence of abdominal pain require surgical treatment; Grade 3 or 4 arterial thromboembolism, including stroke and myocardial infarction;	during the first 21 days
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	Half Life (t1/2) of hPV19	t1/2 is the time required for the plasma/serum concentration to decrease 50%	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.
Secondary	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.
Secondary	Steady State Volume of Distribution (Vss) of hPV19	Vss is the theoretical volume in which the total amount of study drug would need to be uniformly distributed during steady state to produce the same concentration as it is in plasma/serum	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.
Secondary	Best Overall Response [Anti-Tumor Activity of hPV19 Plus Chemotherapy]	Best overall response evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria.; Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Progressive Disease (PD): an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 mm (the appearance of 1 or more new lesions was considered progression). Stable Disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.	Up to six months after 1st treatment or until progression of disease (PD)