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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Advanced Cancer
- Sponsor
- PharmAbcine
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Safety and tolerability
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
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
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
Outcomes
Primary Outcomes
Safety and tolerability
Time Frame: 28days
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 Outcomes
- Pharmacokinetics(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(completion of 2 and more cycle)