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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
BioMed Valley Discoveries, Inc
ClinicalTrials.gov Identifier:
NCT01781429
First received: January 28, 2013
Last updated: January 4, 2017
Last verified: October 2016
  Purpose
This open-label, multi-center Phase 1/2 study will assess the safety, pharmacokinetics, and pharmacodynamics of escalating doses of BVD-523 in patients with advanced malignancies. The study also seeks to demonstrate target modulation and early signs of clinical response in select patient populations.

Condition Intervention Phase
Advanced Solid Tumors
Drug: BVD-523
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies

Further study details as provided by BioMed Valley Discoveries, Inc:

Primary Outcome Measures:
  • Determination of recommended phase 2 dose of BVD-523 determined by dose-limiting toxicities. [ Time Frame: As indicated by safety and tolerability during study conduct; ~42months ]

Secondary Outcome Measures:
  • Characterization of the time versus plasma concentration profiles of BVD-523 and selected metabolites. [ Time Frame: Samples will be collected on day 1 and day 15 of Cycle 1 ]
  • Clinical evidence of tumor response assessed by physical or radiological exam. [ Time Frame: Patients will be evaluated at baseline and at periodic follow-up visits ]

Other Outcome Measures:
  • Pharmacodynamic response assessed by blood and tissue analyses. [ Time Frame: Patients will be evaluated at baseline and on ~day 15 of Cycle 1 ]
    To evaluate pharmacodynamic measures in healthy or malignant tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.

  • Radiographic response assessed using F-fluorodeoxyglucose-positron-emission tomography scans. [ Time Frame: Patients will be evaluated at baseline and day 22 (end of 1st cycle) to identify early response. ]

Estimated Enrollment: 125
Study Start Date: March 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BVD-523 Drug: BVD-523
Oral, multiple escalating doses, twice daily, for 21 days in each treatment cycle

Detailed Description:

The study is being performed to assess the safety and tolerability of BVD-523

In Part 1 of the study, an accelerated dose escalation plan will be used to establish dose limiting toxicities, maximum tolerated dose, and the recommended Phase 2 dose.

In Part 2 of the study, additional patients with particular tumor types and/or cancers harboring specific genetic mutations will be recruited for treatment at the Recommended Phase 2 Dose. Patients may also be assessed pharmacodynamic measures in healthy or malignant tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
    • Group 7: Patients with ERK mutated 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01781429

Locations
United States, California
UCLA Med-Hematology & Oncology
Los Angeles, California, United States, 90095
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520
United States, Florida
Florida Cancer Specialists and Research Group (Sarah Cannon Research Institute)
Sarasota, Florida, United States, 34232
United States, Massachusetts
Massachusetts General Hospital (MGH)
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute Hospital at Vanderbilt
Nashville, Tennessee, United States, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37212
United States, Texas
UT M.D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
BioMed Valley Discoveries, Inc
  More Information

Responsible Party: BioMed Valley Discoveries, Inc
ClinicalTrials.gov Identifier: NCT01781429     History of Changes
Other Study ID Numbers: BVD-523-01  BVD-523-01 
Study First Received: January 28, 2013
Last Updated: January 4, 2017

ClinicalTrials.gov processed this record on January 23, 2017