Phase I Trial of Tanibirumab in Advanced or Metastatic Cancer

NCT ID: NCT01660360

Last Updated: 2014-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2013-09-30

Brief Summary

The primary objective of this study is to assess the safety, tolerability, and maximum tolerated dose (MTD) of Tanibirumab in patients with advanced or metastatic cancer who are refractory or for whom there are no standard therapeutic option.

• To evaluate the pharmacokinetics of Tanibirumab in such patients
• To determine a recommended phase II dose (RP2D) of Tanibirumab based on above assessments

Detailed Description

This is a Phase I, first-in-human, open-label, non-randomized, dose-escalating study of Tanibirumab which is a fully human monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR2/KDR). This study will enroll patients with advanced or metastatic cancer who are refractory or for whom there are no standard therapeutic options. Tanibirumab will be administered intravenously to such patients over 60 minutes on Day 1, 8, and 15 (subject to change pending PK and toxicity data). Each treatment cycle will be a minimum of 28 days in length. The dose escalation study employing a 3 + 3 design is designed to identify the RP2D which will be based on safety, tolerability and PK of the RP2D. This study is expected to enroll a total of approximately 18-24 patients.

Conditions

Advanced Cancer; Metastatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tanibirumab

The total dose of Tanibirumab for each patient will depend on dose level assignment and the patient's weight. Dose levels to be potentially tested in Phase I include: 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, 12 mg/kg, 16 mg/kg, and 20 mg/kg.

Group Type: EXPERIMENTAL

Tanibirumab

Intervention Type: BIOLOGICAL

Interventions

Tanibirumab

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Age > 20 years
• Signed informed consent
• Histologically documented, incurable, locally advanced or metastatic cancers that have failed to respond to at least one prior regimen or for which there is no standard therapy.
• Disease that is measurable or evaluable by RECIST 1.1 criteria (for Solid Tumors)
• ECOG performance status 0-2
• Documented negative pregnancy test for women of childbearing potential and use of an effective means of contraception for both men and women while enrolled in the study
• Granulocyte count ≥ 1,500/㎣, platelet count ≥ 100,000/㎣, and hemoglobin ≥ 9 g/dL
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)(≤ 3 x ULN if liver metastatic cancer)
• Alkline phosphatase, AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastatic cancer)
• Serum creatinine ≤ 1.5 mg/dL
• INR (international normalized ratio) ≤ 1.3, and aPTT (activated partial thromboplastin time) ≤ 1.5 x ULN
• Subject had to have a projected life expectancy of at least 3 months
• Bazetts correction QTc < 450 msec in ECG at Screening

Exclusion Criteria

• Less than 4 weeks since last chemotherapy (including biologic unless previous Avastin treatment, experimental, and hormonal therapy), radiation therapy, or major surgical procedure
• All incisions from any procedure must be fully healed and sutures removed prior to infusion on Day 1
• Pleural effusions, ascites, or leptomeningeal disease as the only manifestation of the current malignancy
• Subjects that have hypertension that is remained uncontrolled, despite drug regimen.
• Subjects with grade III or IV hemorrhage/bleeding and who have experienced pulmonary hemorrhage/hemoptysis (exceed size of 2.5 mL of erythrocyte) or who have experienced grade III/IV hemorrhage/bleeding.
• The presence of gastrointestinal perforation
• The presence of tracheoesophageal fistula or grade Ⅳ fistula
• Subjects with grade Ⅳ proteinuria (nephritic syndrome)
• The presence of arterial thromboembolic events
• Subjects who have history of life threatening (grade Ⅳ) pulmonary embolism
• Subjects with a known hypersensitivity to CHO cell product or other recombined human or humanized antibody
• Subjects with mental illness
• Subjects with a known hypersensitivity to any of the ingredients/substrates in investigational product of this study
• Subjects who given any investigational drug within longer period between 30 days and 5 times of half life before participation in this study
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by drugs
• Clinically important history of liver disease, including viral or other active hepatitis, current alcohol abuse, or cirrhosis
• Known human immunodeficiency virus (HIV) infection
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the subjects at high risk from treatment complications
• Significant traumatic injury within 3 weeks of Day 1
• Inability to comply with study and follow-up procedures

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmAbcine

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Young Seok Park, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Locations

Samsung Medical Center

Seoul, , South Korea

Countries

South Korea

Other Identifiers

PMC1101-TAAC01

Identifier Type: -

Identifier Source: org_study_id