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Trial record 1 of 1 for:    NCT02608229
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BVD-523 Plus Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

This study is currently recruiting participants.
See Contacts and Locations
Verified March 2017 by Washington University School of Medicine
Sponsor:
Collaborator:
BioMed Valley Discoveries, Inc
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02608229
First received: November 16, 2015
Last updated: March 16, 2017
Last verified: March 2017
  Purpose
In light of the central role of extracellular signal-regulated kinases (ERK) in pancreatic cancer, the investigators propose a phase I study to evaluate the ERK inhibitor BVD-523 at the recommended phase 2 dose in combination with nab-paclitaxel plus gemcitabine in patients with newly diagnosed metastatic pancreatic cancer. The primary endpoint will be maximum tolerated dose (MTD) or RP2D and safety. The secondary endpoints include safety, response rate, biochemical response, progression-free survival (PFS) and overall survival (OS). The exploratory endpoints include the assessing the impact of BVD-523 on the MEK/ERK pathway and other major pathway pertain to pancreatic cancer.

Condition Intervention Phase
Pancreatic Cancer Cancer of Pancreas Cancer of the Pancreas Pancreas Cancer Drug: BVD-523 Drug: Nab-paclitaxel Drug: Gemcitabine Procedure: Tumor biopsy Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase Ib Study of BVD-523 Plus Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of treatment regimen [ Time Frame: Completion of cycle 1 for all dose de-escalation patients (approximately 1 year and 1 month) ]
    • The maximum tolerated dose (MTD) is defined as the Dose Level 1 if 0 or 1 dose-limiting toxicities (DLTs) are seen in patients at that dose level or Dose Level -1 if 2+ DLTs are seen in Dose Level 1 but only 0 or 1 DLTs are seen in patients at Dose Level -1.


Secondary Outcome Measures:
  • Safety and toxicity profile of treatment regimen as measured by grade and frequency of adverse events [ Time Frame: 30 days after completion of treatment (estimated to be 28 weeks) ]
    -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

  • Biochemical response of treatment regimen (MTD or above only) [ Time Frame: Completion of treatment (estimated to be 24 weeks) ]
    -The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9

  • Time to tumor progression (TTP) [ Time Frame: Up to 2 years ]
    • Time to tumor progression is defined as the days from registration to time of progressive disease.
    • At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    • At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
    • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    -OS is defined as the days from the date of treatment start and death from any cause. Patients alive or lost to follow-up are censored.


Estimated Enrollment: 25
Actual Study Start Date: June 6, 2016
Estimated Study Completion Date: December 31, 2021
Estimated Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine
  • Treatment will be given in a 28-day cycle.
  • BVD-523 is an oral drug which will given at the protocol-dictated dose on a twice daily basis (at approximately 12-hour intervals).
  • Dose de-escalation patients will take BVD-523 at 600 mg twice daily on its own for two weeks before initiating Cycle 1 treatment with gemcitabine and nab-paclitaxel.
  • Nab-paclitaxel will be given at a dose of 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine will be given at a dose of 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes.
  • Mandatory biopsy at baseline and baseline at end of 2 week BVD-523 lead in.
Drug: BVD-523 Drug: Nab-paclitaxel
Other Names:
  • Abraxane
  • Paclitaxel Albumin-stabilized Nanoparticle Formulation
Drug: Gemcitabine
Other Names:
  • Gemcitabine hydrochloride
  • Gemzar
Procedure: Tumor biopsy
Experimental: Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine
  • Treatment will be given in a 28-day cycle.
  • BVD-523 is an oral drug which will given at the protocol-dictated dose on a twice daily basis (at approximately 12-hour intervals).
  • Nab-paclitaxel will be given at a dose of 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine will be given at a dose of 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes.
  • Mandatory biopsy at baseline and at end of cycle 2 (if deemed safe for participant and feasible to obtain)
Drug: BVD-523 Drug: Nab-paclitaxel
Other Names:
  • Abraxane
  • Paclitaxel Albumin-stabilized Nanoparticle Formulation
Drug: Gemcitabine
Other Names:
  • Gemcitabine hydrochloride
  • Gemzar
Procedure: Tumor biopsy

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed newly diagnosed treatment-naïve metastatic adenocarcinoma of the pancreas with metastatic disease diagnosed no more than 8 weeks prior to enrollment.
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • At least 18 years of age.
  • Life expectancy > 3 months.
  • ECOG performance status ≤ 1
  • Normal bone marrow and organ function as defined below:

    • Absolute neutrophil count ≥ 1,500/mcL
    • Platelets ≥ 100,000/mcL
    • Hemoglobin ≥ 9.0 g/dL
    • Total bilirubin ≤ IULN
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN, unless there are liver metastases in which case AST and ALT ≤ 5.0 x IULN
    • Creatinine ≤ 1.5 x IULN OR GFR of ≥ 50 mL/min
    • Cardiac function ≥ ILLN, e.g., LVEF of > 50% as assessed by MUGA or ECHO, QTc < 470 ms
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for three months following study discontinuation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment.
  • A history of other malignancy with the exception of those treated with curative intent with no evidence of disease for 2 years.
  • Currently receiving any other investigational agents.
  • Known brain metastases or CNS involvement.
  • Significant ascites that require therapeutic paracentesis.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BVD-523, gemcitabine, nab-paclitaxel, or other agents used in the study.
  • Neuropathy ≥ grade 1.
  • History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
  • History of interstitial lung disease or pneumonitis.
  • Concurrent therapy with drugs known to be strong inhibitors of CYP1A2, CYP2D6, and CYP3A4, or strong inducers of CYP3A4 (see Appendix B).
  • Gastrointestinal condition which could impair absorption of BVD-523 or inability to ingest BVD-523.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
  • Known HIV-positivity.
  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: NCT02608229

Contacts
Contact: Andrea Wang-Gillam, M.D., Ph.D. (314) 362-5740 awang-gillam@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Andrea Wang-Gillam, M.D., Ph.D.    314-362-5740    awang-gillam@wustl.edu   
Principal Investigator: Andrea Wang-Gillam, M.D., Ph.D.         
Sub-Investigator: Manik Anin, M.D.         
Sub-Investigator: Eric Knoche, M.D.         
Sub-Investigator: Kian-Huat Lim, M.D., Ph.D.         
Sub-Investigator: A. Craig Lockhart, M.D.         
Sub-Investigator: Kathryn Robinson, M.D.         
Sub-Investigator: Alex Politsmakher, M.D.         
Sub-Investigator: Caron Rigden, M.D.         
Sub-Investigator: Preet Singh, M.D.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Ben Tan, M.D.         
Sub-Investigator: Ashiq Masood, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
BioMed Valley Discoveries, Inc
Investigators
Principal Investigator: Andrea Wang-Gillam, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02608229     History of Changes
Other Study ID Numbers: 201601098
Study First Received: November 16, 2015
Last Updated: March 16, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 27, 2017