Back to results

Phase I Trial of Tanibirumab in Advanced or Metastatic Cancer

Primary Purpose

Advanced Cancer, Metastatic Cancer

Status

Completed

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Tanibirumab

About this trial

This is an interventional treatment trial for Advanced Cancer focused on measuring Tanibirumab Phase I trial

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Samsung Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tanibirumab

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

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

Full Information

NCT ID

NCT01660360

First Posted

August 6, 2012

Last Updated

January 27, 2014

Sponsor

PharmAbcine

1. Study Identification

Unique Protocol Identification Number

NCT01660360

Brief Title

Phase I Trial of Tanibirumab in Advanced or Metastatic Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2014

Overall Recruitment Status

Completed

Study Start Date

November 2011 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PharmAbcine

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Cancer, Metastatic Cancer

Keywords

Tanibirumab Phase I trial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tanibirumab

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Tanibirumab

Primary Outcome Measure Information:

Title

Safety and tolerability

Description

Time Frame

28days

Secondary Outcome Measure Information:

Title

Pharmacokinetics

Description

Time Frame

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.

Title

Efficacy

Description

Time Frame

completion of 2 and more cycle

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Young Seok Park, MD, PhD

Organizational Affiliation

Samsung Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Samsung Medical Center

City

Seoul

ZIP/Postal Code

135-230

Country

Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

Phase I Trial of Tanibirumab in Advanced or Metastatic Cancer

We'll reach out to this number within 24 hrs