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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

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ClinicalTrials.gov Identifier: NCT02608229
Recruitment Status : Terminated (Adverse events)
First Posted : November 18, 2015
Results First Posted : May 1, 2020
Last Update Posted : June 4, 2020
Sponsor:
Collaborators:
BioMed Valley Discoveries, Inc
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Pancreatic Cancer
Cancer of Pancreas
Cancer of the Pancreas
Pancreas Cancer
Interventions Drug: BVD-523
Drug: Nab-paclitaxel
Drug: Gemcitabine
Procedure: Tumor biopsy
Enrollment 18
Recruitment Details The study opened to participant enrollment on 06/06/2016 and closed to participant enrollment on 08/19/2019.
Pre-assignment Details  
Arm/Group Title Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine
Hide Arm/Group Description
  • Treatment will be given in a 28-day cycle.
  • BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals).
  • 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 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 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.
  • Treatment will be given in a 28-day cycle.
  • First 2 patients enrolled: BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
  • Remaining 6 patients enrolled: BVD-523 450 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 800 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)
Period Title: Overall Study
Started 10 8
600 mg BVD-523 10 2
450 mg BVD-523 0 6
Completed 10 8
Not Completed 0 0
Arm/Group Title Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine Total
Hide Arm/Group Description
  • Treatment will be given in a 28-day cycle.
  • BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals).
  • 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 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 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.
  • Treatment will be given in a 28-day cycle.
  • First 2 patients enrolled: BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
  • Remaining 6 patients enrolled: BVD-523 450 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 800 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)
Total of all reporting groups
Overall Number of Baseline Participants 10 8 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants 8 participants 18 participants
65.5
(55 to 74)
61.5
(37 to 78)
63.5
(37 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
Female
3
  30.0%
2
  25.0%
5
  27.8%
Male
7
  70.0%
6
  75.0%
13
  72.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
10
 100.0%
8
 100.0%
18
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
10
 100.0%
7
  87.5%
17
  94.4%
More than one race
0
   0.0%
1
  12.5%
1
   5.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 8 participants 18 participants
10 8 18
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of BVD-523
Hide Description -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.
Time Frame Completion of cycle 1 for all dose de-escalation patients (1.8 years), the first cycle is 28 days for each individual patient
Hide Outcome Measure Data
Hide Analysis Population Description
-The MTD was not determined by DLTs in Dose De-escalation. 2 patients in Dose Expansion were treated at 600 mg but due to poor performance (inability to complete Cycle 1) the principal investigator felt it was reasonable to treat the remaining patients with 450 mg BVD-523 twice daily in the dose expansion portion of the study.
Arm/Group Title Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine
Hide Arm/Group Description:
  • Treatment will be given in a 28-day cycle.
  • BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals).
  • 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 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 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.
  • Treatment will be given in a 28-day cycle.
  • First 2 patients enrolled: BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
  • Remaining 6 patients enrolled: BVD-523 450 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 800 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)
Overall Number of Participants Analyzed 10 0
Measure Type: Number
Unit of Measure: mg
450
2.Secondary Outcome
Title Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events
Hide Description -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.
Time Frame 30 days after completion of treatment (median time was 67.5 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 600 mg BVD-523/Nab-paclitaxel/Gemcitabine 450 mg BVD-523/Nab-paclitaxel/Gemcitabine
Hide Arm/Group Description:
  • Treatment will be given in a 28-day cycle.
  • All patients who received 600 mg BVD-523 on a twice daily basis (at approximately 12-hour intervals) are included in this group
  • Nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes.
  • Treatment will be given in a 28-day cycle.
  • All patients who received 450 mg BVD-523 on a twice daily basis (at approximately 12-hour intervals) are included in this group
  • Nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 800 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes.
Overall Number of Participants Analyzed 12 6
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1/2 Hearing Impaired
1
   8.3%
0
   0.0%
Grade 1/2 blurred vision
3
  25.0%
0
   0.0%
Grade 3 abdominal infection
1
   8.3%
0
   0.0%
Grade 1/2 constipation
5
  41.7%
2
  33.3%
Grade 1/2 diarrhea
5
  41.7%
4
  66.7%
Grade 3 diarrhea
2
  16.7%
0
   0.0%
Grade 1/2 dry mouth
2
  16.7%
0
   0.0%
Grade 1/2 dyspepsia
1
   8.3%
1
  16.7%
Grade 1/2 flatulence
1
   8.3%
0
   0.0%
Grade 1/2 gastrointestinal pain
1
   8.3%
0
   0.0%
Grade 1/2 mucositis oral
2
  16.7%
2
  33.3%
Grade 1/2 nausea
5
  41.7%
1
  16.7%
Grade 3 nausea
1
   8.3%
1
  16.7%
Grade 1/2 taste change
1
   8.3%
0
   0.0%
Grade 1/2 vomiting
0
   0.0%
1
  16.7%
Grade 3 vomiting
2
  16.7%
1
  16.7%
Grade 1/2 acute kidney injury
1
   8.3%
0
   0.0%
Grade 3 lower GI hemorrhage
1
   8.3%
0
   0.0%
Grade 1/2 chills
3
  25.0%
1
  16.7%
Grade 1/2 edema limbs
3
  25.0%
1
  16.7%
Grade 1/2 edema trunk
1
   8.3%
0
   0.0%
Grade 1/2 fatigue
3
  25.0%
2
  33.3%
Grade 1/2 fever
5
  41.7%
2
  33.3%
Grade 1/2 thrush
1
   8.3%
1
  16.7%
Grade 5 death due to disease progression
1
   8.3%
1
  16.7%
Grade 1/2 alanine aminotransferase increased
2
  16.7%
0
   0.0%
Grade 1/2 alkaline phosphtase
2
  16.7%
0
   0.0%
Grade 4 blood bilirubin increased
1
   8.3%
0
   0.0%
Grade 3/4 neutrophil count decreased
3
  25.0%
1
  16.7%
Grade 3 platelet count decreased
1
   8.3%
1
  16.7%
Grade 1/2 lymphocyte count
1
   8.3%
0
   0.0%
Grade 1/2 white blood cell count decreased
2
  16.7%
0
   0.0%
Grade 1/2 hypercalcemia
2
  16.7%
0
   0.0%
Grade 1/2 hyperglycemia
1
   8.3%
0
   0.0%
Grade 1/2 hyperkalemia
2
  16.7%
0
   0.0%
Grade 1/2 hypoalbuminemia
1
   8.3%
0
   0.0%
Grade 1/2 hypocalcemia
1
   8.3%
0
   0.0%
Grade 1/2 dehydration
1
   8.3%
1
  16.7%
Grade 1/2 arthralgia
4
  33.3%
1
  16.7%
Grade 1/2 back pain
2
  16.7%
0
   0.0%
Grade 1/2 dizziness
4
  33.3%
1
  16.7%
Grade 1/2 headache
3
  25.0%
0
   0.0%
Grade 1/2 peripheral sensory neuropathy
5
  41.7%
0
   0.0%
Grade 1/2 numbness
1
   8.3%
0
   0.0%
Grade 1/2 insomnia
2
  16.7%
1
  16.7%
Grade 1/2 anxiety
1
   8.3%
1
  16.7%
Grade 1/2 cough
1
   8.3%
1
  16.7%
Grade 1/2 dyspnea
2
  16.7%
0
   0.0%
Grade 1/2 epistaxis
1
   8.3%
0
   0.0%
Grade 5 adult respiratory distress syndrome
1
   8.3%
0
   0.0%
Grade 1/2 alopecia
5
  41.7%
3
  50.0%
Grade 1/2 rash acneiform
3
  25.0%
4
  66.7%
Grade 3 rash acneiform
2
  16.7%
0
   0.0%
Grade 1/2 rash maculo-papular
4
  33.3%
0
   0.0%
Grade 1/2 sweating
1
   8.3%
0
   0.0%
Grade 1 scalp sun burned
1
   8.3%
0
   0.0%
Grade 1/2 hypertension
3
  25.0%
0
   0.0%
Grade 3 hypertension
1
   8.3%
0
   0.0%
Grade 1/2 hyperhydrosis
0
   0.0%
1
  16.7%
Grade 1/2 pruritus
0
   0.0%
1
  16.7%
Grade 1/2 myalgia
0
   0.0%
1
  16.7%
Grade 1/2 blood in stool
0
   0.0%
1
  16.7%
Grade 1/2 anorexia
3
  25.0%
1
  16.7%
Grade 3 anorexia
0
   0.0%
1
  16.7%
Grade 1/2 abdominal pain
2
  16.7%
2
  33.3%
Grade 3 abdominal pain
0
   0.0%
1
  16.7%
Grade 3 portal vein thrombosis
0
   0.0%
1
  16.7%
Grade 3 lung infection
0
   0.0%
1
  16.7%
Grade 1/2 anemia
3
  25.0%
1
  16.7%
Grade 3 anemia
0
   0.0%
1
  16.7%
3.Secondary Outcome
Title Response Rate
Hide Description
  • Response rate is the percentage of participants with best response of complete response or partial response per RECIST 1.1
  • Complete response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
  • Partial response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Through completion of treatment (median time was 37.5 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who did not have a follow-up CT scan were excluded from this outcome measure. The 2 participants analyzed in the Dose Expansion arm received 450 mg of BVD-523.
Arm/Group Title Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine
Hide Arm/Group Description:
  • Treatment will be given in a 28-day cycle.
  • BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals).
  • 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 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 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.
  • Treatment will be given in a 28-day cycle.
  • First 2 patients enrolled: BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
  • Remaining 6 patients enrolled: BVD-523 450 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 800 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)
Overall Number of Participants Analyzed 5 2
Measure Type: Count of Participants
Unit of Measure: Participants
2
  40.0%
0
   0.0%
4.Secondary Outcome
Title Biochemical Response of Treatment Regimen
Hide Description -The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9
Time Frame Through completion of treatment (median time was 37.5 days)
Hide Outcome Measure Data
Hide Analysis Population Description
-Participants with normal CA19-9 levels at baseline were excluded from this outcome measure and those who did not have an additional CA19-9 level drawn after baseline. Of the 5 participants analyzed in Dose Expansion Arm, 1 received 600 mg BVD-523 and 4 participants received 450 mg BVD-523.
Arm/Group Title Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine
Hide Arm/Group Description:
  • Treatment will be given in a 28-day cycle.
  • BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals).
  • 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 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 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.
  • Treatment will be given in a 28-day cycle.
  • First 2 patients enrolled: BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
  • Remaining 6 patients enrolled: BVD-523 450 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 800 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)
Overall Number of Participants Analyzed 7 5
Measure Type: Count of Participants
Unit of Measure: Participants
3
  42.9%
1
  20.0%
5.Secondary Outcome
Title Time to Tumor Progression (TTP)
Hide Description
  • Time to tumor progression is defined as the days from start of treatment until progressive disease.
  • Progression is defined as 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).
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who did not have a follow-up CT scan were excluded from this outcome measure. The 2 participants analyzed in the Dose Expansion Arm received 450 mg BVD-523.
Arm/Group Title Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine
Hide Arm/Group Description:
  • Treatment will be given in a 28-day cycle.
  • BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals).
  • 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 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 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.
  • Treatment will be given in a 28-day cycle.
  • First 2 patients enrolled: BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
  • Remaining 6 patients enrolled: BVD-523 450 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 800 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)
Overall Number of Participants Analyzed 5 2
Median (Full Range)
Unit of Measure: days
85
(63 to 243)
39.5
(30 to 49)
6.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description
  • Progression is defined as 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. Patients alive without progression or lost to follow-up are censored.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who did not have a follow-up CT scan were excluded from this outcome measure. The 2 participants analyzed in the Dose Expansion Arm received 450 mg BVD-523.
Arm/Group Title Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine
Hide Arm/Group Description:
  • Treatment will be given in a 28-day cycle.
  • BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals).
  • 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 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 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.
  • Treatment will be given in a 28-day cycle.
  • First 2 patients enrolled: BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
  • Remaining 6 patients enrolled: BVD-523 450 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 800 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)
Overall Number of Participants Analyzed 5 2
Median (Full Range)
Unit of Measure: days
85
(63 to 243)
39.5
(30 to 49)
7.Secondary Outcome
Title Overall Survival (OS)
Hide Description -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.
Time Frame Up to 2 years
Outcome Measure Data Not Reported
Time Frame Adverse events were collected from start of study treatment until 30 days following completion of study treatment. Median length of follow-up for adverse events was 67.5 days. One patient in dose expansion is still being followed for all-cause mortality.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 600 mg BVD-523/Nab-paclitaxel/Gemcitabine 450 mg BVD-523/Nab-paclitaxel/Gemcitabine
Hide Arm/Group Description
  • Treatment will be given in a 28-day cycle.
  • All patients who received 600 mg BVD-523 on a twice daily basis (at approximately 12-hour intervals) are included in this group
  • Nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes.
  • Treatment will be given in a 28-day cycle.
  • All patients who received 450 mg BVD-523 on a twice daily basis (at approximately 12-hour intervals) are included in this group
  • Nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
  • Gemcitabine 800 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes.
All-Cause Mortality
600 mg BVD-523/Nab-paclitaxel/Gemcitabine 450 mg BVD-523/Nab-paclitaxel/Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   11/12 (91.67%)   4/6 (66.67%) 
Hide Serious Adverse Events
600 mg BVD-523/Nab-paclitaxel/Gemcitabine 450 mg BVD-523/Nab-paclitaxel/Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   8/12 (66.67%)   4/6 (66.67%) 
Blood and lymphatic system disorders     
Anemia  1  0/12 (0.00%)  1/6 (16.67%) 
Gastrointestinal disorders     
Abdominal pain  1  0/12 (0.00%)  1/6 (16.67%) 
Diarrhea  1  1/12 (8.33%)  0/6 (0.00%) 
Lower GI hemorrhage  1  1/12 (8.33%)  0/6 (0.00%) 
Nausea  1  1/12 (8.33%)  1/6 (16.67%) 
Vomiting  1  1/12 (8.33%)  0/6 (0.00%) 
General disorders     
Death due to disease progression  1  1/12 (8.33%)  1/6 (16.67%) 
Fever  1  5/12 (41.67%)  0/6 (0.00%) 
Infections and infestations     
Abdominal infection  1  1/12 (8.33%)  0/6 (0.00%) 
Lung infection  1  0/12 (0.00%)  1/6 (16.67%) 
Investigations     
Blood bilirubin increased  1  1/12 (8.33%)  0/6 (0.00%) 
Neutrophil count decreased  1  1/12 (8.33%)  0/6 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  0/12 (0.00%)  1/6 (16.67%) 
Renal and urinary disorders     
Acute kidney injury  1  1/12 (8.33%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  1  1/12 (8.33%)  0/6 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
600 mg BVD-523/Nab-paclitaxel/Gemcitabine 450 mg BVD-523/Nab-paclitaxel/Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders     
Anemia  1  3/12 (25.00%)  1/6 (16.67%) 
Ear and labyrinth disorders     
Hearing impaired  1  1/12 (8.33%)  0/6 (0.00%) 
Eye disorders     
Blurred vision  1  3/12 (25.00%)  0/6 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  2/12 (16.67%)  2/6 (33.33%) 
Constipation  1  5/12 (41.67%)  2/6 (33.33%) 
Diarrhea  1  6/12 (50.00%)  4/6 (66.67%) 
Dry mouth  1  2/12 (16.67%)  0/6 (0.00%) 
Dyspepsia  1  1/12 (8.33%)  1/6 (16.67%) 
Flatulence  1  1/12 (8.33%)  0/6 (0.00%) 
Gastrointestinal pain  1  1/12 (8.33%)  0/6 (0.00%) 
Mucositis oral  1  2/12 (16.67%)  2/6 (33.33%) 
Nausea  1  5/12 (41.67%)  1/6 (16.67%) 
Taste change  1  1/12 (8.33%)  0/6 (0.00%) 
Vomiting  1  1/12 (8.33%)  2/6 (33.33%) 
Blood in stool  1  0/12 (0.00%)  1/6 (16.67%) 
General disorders     
Chills  1  3/12 (25.00%)  1/6 (16.67%) 
Edema limb  1  3/12 (25.00%)  1/6 (16.67%) 
Edema trunk  1  1/12 (8.33%)  0/6 (0.00%) 
Fatigue  1  3/12 (25.00%)  2/6 (33.33%) 
Fever  1  0/12 (0.00%)  2/6 (33.33%) 
Thrush  1  1/12 (8.33%)  1/6 (16.67%) 
Investigations     
Alanine aminotransferase increased  1  2/12 (16.67%)  0/6 (0.00%) 
Alkaline phosphatase increased  1  2/12 (16.67%)  0/6 (0.00%) 
Neutrophil count decreased  1  2/12 (16.67%)  1/6 (16.67%) 
Platelet count decreased  1  1/12 (8.33%)  1/6 (16.67%) 
Lymphocyte count decreased  1  1/12 (8.33%)  0/6 (0.00%) 
White blood cell decreased  1  2/12 (16.67%)  0/6 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  3/12 (25.00%)  1/6 (16.67%) 
Hypercalcemia  1  2/12 (16.67%)  0/6 (0.00%) 
Hyperglycemia  1  1/12 (8.33%)  0/6 (0.00%) 
Hyperkalemia  1  2/12 (16.67%)  0/6 (0.00%) 
Hypoalbuminemia  1  1/12 (8.33%)  0/6 (0.00%) 
Hypocalcemia  1  1/12 (8.33%)  0/6 (0.00%) 
Dehydration  1  1/12 (8.33%)  1/6 (16.67%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/12 (33.33%)  1/6 (16.67%) 
Back pain  1  2/12 (16.67%)  0/6 (0.00%) 
Nervous system disorders     
Dizziness  1  4/12 (33.33%)  1/6 (16.67%) 
Headache  1  3/12 (25.00%)  0/6 (0.00%) 
Peripheral sensory neuropathy  1  5/12 (41.67%)  0/6 (0.00%) 
Numbness  1  1/12 (8.33%)  0/6 (0.00%) 
Psychiatric disorders     
Insomnia  1  2/12 (16.67%)  1/6 (16.67%) 
Anxiety  1  1/12 (8.33%)  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/12 (8.33%)  1/6 (16.67%) 
Dyspnea  1  2/12 (16.67%)  0/6 (0.00%) 
Epistaxis  1  1/12 (8.33%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  5/12 (41.67%)  3/6 (50.00%) 
Rash acneiform  1  5/12 (41.67%)  4/6 (66.67%) 
Rash maculo-papular  1  4/12 (33.33%)  0/6 (0.00%) 
Sweating  1  1/12 (8.33%)  0/6 (0.00%) 
Scalp sun burned  1  1/12 (8.33%)  0/6 (0.00%) 
Hyperhydrosis  1  0/12 (0.00%)  1/6 (16.67%) 
Pruritus  1  0/12 (0.00%)  1/6 (16.67%) 
Vascular disorders     
Hypertension  1  4/12 (33.33%)  0/6 (0.00%) 
Portal vein thrombosis  1  0/12 (0.00%)  1/6 (16.67%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Andrea Wang-Gillam, M.D., Ph.D.
Organization: Washington University School of Medicine
Phone: 314-362-5740
EMail: awang-gillam@wustl.edu
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02608229    
Other Study ID Numbers: 201601098
5P50CA196510-02 ( U.S. NIH Grant/Contract )
First Submitted: November 16, 2015
First Posted: November 18, 2015
Results First Submitted: March 27, 2020
Results First Posted: May 1, 2020
Last Update Posted: June 4, 2020