Phase I Trial of Tanibirumab in Advanced or Metastatic Cancer

A Phase I Study of the Safety and Pharmacokinetics of a Fully Human Monoclonal Antibody to the Vascular Endothelial Growth Factor Receptor2 (Tanibirumab) in Patients With Advanced Cancers or Metastatic Cancer

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

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer; Advanced Cancer
• Intervention / Treatment: Biological: Tanibirumab

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-230
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Tanibirumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	The safety and tolerability of Tanibirumab will be assessed using the following measures: frequency and nature of dose-limiting toxicities (DLTs); nature, severity, and relatedness of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v4.0; changes in vital signs; and changes in clinical laboratory parameters.	28days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	The following PK parameters will be derived from the serum concentration-time profile of Tanibirumab following administration: serum total exposure (AUC), Cmax, clearance, volume of distribution (central compartment Vc and at steady state Vss), and half-life (t½).	Cycle 1 : predose, 0.5, 2, 4, 24 and 72 hours after 1st dose, predose and 0.5 hours after 2nd dose, predose, 0.5, 2, 4, 24, 72, 168 and 336 hours after 3rd dose. After cycle 2: predose of 1st dose and 0.5 hour after 3rd dose.
Efficacy	The following activity outcome measures will be assessed: objective response, defined as a complete or partial response confirmed 4 weeks after initial documentation; duration of objective response; and progression-free survival. Objective response and disease progression will be determined using RECIST 1.1	completion of 2 and more cycle

Collaborators and Investigators

• Sponsor: PharmAbcine
• Investigators: Principal Investigator: Young Seok Park, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: August 6, 2012
• First Submitted That Met QC Criteria: August 6, 2012
• First Posted (Estimate): August 8, 2012

Study Record Updates

• Last Update Posted (Estimate): January 29, 2014
• Last Update Submitted That Met QC Criteria: January 27, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Tanibirumab Phase I trial
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary
• Other Study ID Numbers: PMC1101-TAAC01