Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

* 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)

BVD-523

Nab-paclitaxel

Tumor biopsy

Kian-Huat Lim, M.D., Ph.D.

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.

BVD-523 Plus Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

Phase Ib Study of BVD-523 Plus Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

-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.

-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.

* 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.

-The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9

* 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).

* 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.

-OS is defined as the days from the date of treatment start and death from any cause. Participants alive or lost to follow-up are censored.

BioMed Valley Discoveries, Inc

National Cancer Institute (NCI)

Washington University School of Medicine

* 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.

600 mg BVD-523/Nab-paclitaxel/Gemcitabine

* 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.

450 mg BVD-523/Nab-paclitaxel/Gemcitabine

Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine

Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

-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.

Maximum Tolerated Dose (MTD) of BVD-523

Grade 1/2 Hearing Impaired

Grade 1/2 blurred vision

Grade 3 abdominal infection

Grade 1/2 constipation

Grade 1/2 diarrhea

Grade 3 diarrhea

Grade 1/2 dry mouth

Grade 1/2 dyspepsia

Grade 1/2 flatulence

Grade 1/2 gastrointestinal pain

Grade 1/2 mucositis oral

Grade 1/2 nausea

Grade 3 nausea

Grade 1/2 taste change

Grade 1/2 vomiting

Grade 3 vomiting

Grade 1/2 acute kidney injury

Grade 3 lower GI hemorrhage

Grade 1/2 chills

Grade 1/2 edema limbs

Grade 1/2 edema trunk

Grade 1/2 fatigue

Grade 1/2 fever

Grade 1/2 thrush

Grade 5 death due to disease progression

Grade 1/2 alanine aminotransferase increased

Grade 1/2 alkaline phosphtase

Grade 4 blood bilirubin increased

Grade 3/4 neutrophil count decreased

Grade 3 platelet count decreased

Grade 1/2 lymphocyte count

Grade 1/2 white blood cell count decreased

Grade 1/2 hypercalcemia

Grade 1/2 hyperglycemia

Grade 1/2 hyperkalemia

Grade 1/2 hypoalbuminemia

Grade 1/2 hypocalcemia

Grade 1/2 dehydration

Grade 1/2 arthralgia

Grade 1/2 back pain

Grade 1/2 dizziness

Grade 1/2 headache

Grade 1/2 peripheral sensory neuropathy

Grade 1/2 numbness

Grade 1/2 insomnia

Grade 1/2 anxiety

Grade 1/2 cough

Grade 1/2 dyspnea

Grade 1/2 epistaxis

Grade 5 adult respiratory distress syndrome

Grade 1/2 alopecia

Grade 1/2 rash acneiform

Grade 3 rash acneiform

Grade 1/2 rash maculo-papular

Grade 1/2 sweating

Grade 1 scalp sun burned

Grade 1/2 hypertension

Grade 3 hypertension

Grade 1/2 hyperhydrosis

Grade 1/2 pruritus

Grade 1/2 myalgia

Grade 1/2 blood in stool

Grade 1/2 anorexia

Grade 3 anorexia

Grade 1/2 abdominal pain

Grade 3 abdominal pain

Grade 3 portal vein thrombosis

Grade 3 lung infection

Grade 1/2 anemia

Grade 3 anemia

Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events

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.

Response Rate

-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.

Biochemical Response of Treatment Regimen

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.

Time to Tumor Progression (TTP)

Progression-free Survival (PFS)

Participants were not considered evaluable for this outcome measure if they were not evaluable for dose-limiting toxicities per protocol and any participants that were alive were censored.

Overall Survival (OS)

Overall Study

Spots Global Cancer Trial Database for BVD-523 Plus Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial