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

This study is currently recruiting participants.
Verified January 2014 by BioMed Valley Discoveries, Inc
Sponsor:
Information provided by (Responsible Party):
BioMed Valley Discoveries, Inc
ClinicalTrials.gov Identifier:
NCT01781429
First received: January 28, 2013
Last updated: January 31, 2014
Last verified: January 2014
  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: Endpoint Classification: Safety Study
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Determination of recommended phase 2 dose (RP2D) of BVD-523 determined by dose-limiting toxicities. [ Time Frame: Until safety and tolerability limit further dose escalation; up to ~18 months ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]
  • Clinical evidence of tumor response assessed by physical or radiological exam. [ Time Frame: Patients will be evaluated at baseline and at 60 days ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
    To evaluate pharmacodynamic measures in healthy or malignant tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.

  • Radiographic response assessed using using F-fluorodeoxyglucose-positron-emission tomography (FDG-PET) scans. [ Time Frame: Patients will be evaluated at baseline and day 22 (end of 1st cycle) to identify early response. ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: March 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (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 given orally, twice daily for 21-day cycles.

In Part 1 of the study, an accelerated dose escalation plan will be used to establish dose limiting toxicities (DLT), maximum tolerated dose (MTD), and the recommended Phase 2 dose (RP2D).

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 (RP2D). 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with metastatic or advanced-stage malignant tumor, confirmed histologically, for whom no therapy exists that would be curative. Patients may have received up to 2 prior lines of chemotherapy for their metastatic disease.
  • ECOG performance status of 0 or 1
  • Predicted life expectancy of ≥ 3 months
  • Adequate bone marrow, liver and renal function renal function as assessed by the following laboratory requirements:

    1. creatinine ≤ 1.5 times ULN (upper limit of normal)] and/or GFR of ≥ 50mL/min
    2. total bilirubin ≤ 1.5 x UNL; AST (aspartate transaminase) and/or ALT (alanine transaminase) ≤ 3x UNL or ≤ 5 x UNL if due to liver involvement by tumor
    3. hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x 10 cells/L; absolute neutrophil count ≥ 1.5 x 109 cells/L
  • Adequate cardiac function, e.g. [left ventricular ejection fraction (LVEF) of > 50%; corrected QT interval (QTc) < 470 ms]
  • 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 following 4 groups:

    1. Patients with BRAF mutated melanoma; not previously treated with inhibitors of BRAF, MEK, or ERK
    2. Patients with BRAF mutated melanoma who have progressed while being treated with BRAF inhibitors.
    3. Patients with BRAF mutated non-melanoma; not previously treated with inhibitors of BRAF, MEK, or ERK
    4. Patients with RAS mutated advanced malignancy; not previously treated with inhibitors of BRAF, MEK, or ERK

Exclusion Criteria:

  • Gastrointestinal (GI) 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, with no dose change in the previous 4 weeks, can be allowed
  • 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. A minimum of 10 days between termination of the investigational drug and administration of BVD-523 is required. In addition, any drug- related toxicity except alopecia should have recovered to Grade 1 or less
  • 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 (RVO) or central serous retinopathy (CSR)
  • Concurrent therapy with any other investigational agent
  • Concurrent therapy with drugs known to be strong inhibitors of CYP1A2, CYP2D6, or CYP3A4, or strong inducers of CYP3A4.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01781429

Contacts
Contact: Saurabh Saha, MD, PhD 816-960-4661 ssaha@biomed-valley.com

Locations
United States, California
UCLA Med-Hematology & Oncology Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Phyllis Wu    310-794-0738    zpwu@mednet.ucla.edu   
Sub-Investigator: Antoni Ribas, MD         
Principal Investigator: Deborah Wong, M.D., Ph.D.         
United States, Connecticut
Sarah Cannon Research Institute/Yale Cancer Center Not yet recruiting
New Haven, Connecticut, United States, 06520
Contact: Matthew Madura    203-737-5381    matthew.madura@yale.edu   
Principal Investigator: Paul Eder, MD         
United States, Florida
Florida Cancer Specialists and Research Group (Sarah Cannon Research Institute) Recruiting
Sarasota, Florida, United States, 34232
Contact: Jill Martin, RN    941-377-9993 ext 319    jimartin@flcancer.com   
Principal Investigator: Manish Patel, MD         
United States, Massachusetts
Massachusetts General Hospital (MGH) Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Dennise Martinez    617-724-0695    dmartinez7@partners.org   
Principal Investigator: Keith Flaherty, MD         
United States, Tennessee
Sarah Cannon Research Institute Hospital at Vanderbilt Recruiting
Nashville, Tennessee, United States, 37203
Contact: Suzanne Jones, PhD    615-329-7274    Suzanne.jones@scresearch.net   
Principal Investigator: Jeffrey Infante, MD         
Principal Investigator: Howard Burris, MD         
Sponsors and Collaborators
BioMed Valley Discoveries, Inc
  More Information

No publications provided

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 31, 2014
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on April 16, 2014