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Clinical Trial VICCPHI1375


Phase I Dose Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients with Advanced Malignancies BVD-523-01

Principal Investigator(s)

Jeffrey Sosman


  • Protocol No. VICCPHI1375
  • Open Date: 05/16/2014
  • Staging: Phase I
  • Age Group: Adults
  • Scope: National
  • Objective: To define the safety and tolerability of BVD-523 in patients with advanced malignancies by determining the dose-limiting toxicities (DLT), the maximum tolerated dose (MTD), and the recommended Phase 2 Dose (RP2D)
  • Disease Sites: Phase I
  • Therapies: Molecular Targeted Agents / Immunotherapy / Biologics
  • Drugs: BVD-523
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT01781429
  • Secondary Protocol No: BVD-523-01


Patients are asked to take part in this research study because they have cancer that has not responded to treatment or for which there is no standard treatment. The purpose of the study is to test the safety of an experimental drug, BVD-523, at different dose levels. We want to find out what effects, good and/or bad, it has on patients and their cancer. The primary objective of this study is to define the maximum tolerated dose (MTD), the dose-limiting toxicities (DLT), and the recommended Phase 2 dose. This study is a two part study. The study doctor will tell the patient which part and dose level they will be participating in prior to their enrollment. Which part and dose level the patient is assigned to is determined by the timing of their enrollment into the study. In both parts of the study BVD-523 will be taken twice daily as pills for 21-day cycles. We will do some tests and procedures to monitor both the patient's cancer and their safety. Part I (Dose Escalation Phase): Part I (Dose Escalation Phase) will look at the safety of increasing dose levels of the study drug, BVD-523, in patients with advanced malignancies. Each dose group will initially include between 1-6 patients until the maximum tolerated dose (MTD) is reached and an acceptable Phase 2 dose is identified. The study doctors at Vanderbilt and at other hospitals participating in this study and the Sponsor will review the safety data of each dose level of the study drug following 21 days of dosing, before the patients in the next dose level are dosed and before Part 2 of the study can start. How the study drug affects your body will be tracked. Once an acceptable Phase 2 dose is identified in Part 1, then Part 2 of the study will commence, using that dose. Approximately 40 patients will be dosed in Part 1. Part 2 (Cohort Expansion Phase): Part 2 (Cohort Expansion Phase) of the study will look at the safety of study drug, BVD-523, and any possible signs of cancer response in patients with specific cancer types (determined by genetic tumor characteristics) and prior treatment history. There will be five treatment groups assigned by cancer disease characteristics. Each of the 5 groups will include between 10 - 15 patients with a total enrollment of approximately 70 additional patients. The dose in Part 2 will be the recommended Phase 2 dose determined from Part 1. How the study drug affects the patient's body will be tracked. BVD-523 is considered investigational, which means that it has not been approved by the U.S. Food and Drug Administration.


Ages Eligible for Study:18 Years and older
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No


Inclusion Criteria:
• Patients with metastatic or advanced-stage malignant tumor. Patients may have received up to 2 prior lines of chemotherapy for their metastatic disease
• ECOG score of 0 or 1
• Predicted life expectancy of ≥ 3 months
• Adequate bone marrow, liver and renal function renal function
• Adequate cardiac function
• For women: Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal, or compliant with a contraceptive regimen during and for 3 months after the treatment period
• For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 3 months after the treatment period
• For Part 2 of the Study only, patients must have measurable disease by RECIST 1.1 and be in one of the the groups below. Patients in groups 1, 2, 4, 5 and 6 may not have been previously treated with BRAF and/or MEK inhibitors
• Group 1: Patients with BRAF mutated cancer, except those with colorectal or non-small cell lung cancers
• Group 2: Patients with BRAF mutated colorectal cancer
• Group 3: Patients with BRAF mutated melanoma who have progressed on, or are refractory to BRAF and/or MEK inhibitors
• Group 4: Patients with NRAS mutated melanoma
• Group 5: Patients with MEK mutated cancer
• Group 6: Patients with BRAF mutated non-small cell lung cancer
Exclusion Criteria:
• Gastrointestinal condition which could impair absorption of study medication
• Uncontrolled or severe intercurrent medical condition
• Known uncontrolled brain metastases. Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants
• Any cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days or 5 half-lives, whichever is shorter
• Major surgery within 4 weeks prior to first dose
• Any use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of BVD-523.
• Pregnant or breast-feeding women
• Any evidence of serious active infections
• Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study
• A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
• Concurrent therapy with any other investigational agent
• Concomitant malignancies or previous malignancies with less than 2 years disease-free interval at the time of enrollment