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| ID | Type | Description | Link |
|---|---|---|---|
| 5P50CA196510-02 | U.S. NIH Grant/Contract | View source |
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Adverse events
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| Name | Class |
|---|---|
| BioMed Valley Discoveries, Inc | INDUSTRY |
| National Cancer Institute (NCI) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Experimental |
|
|
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Experimental |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BVD-523 | Drug |
| ||
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of BVD-523 | -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. | Completion of cycle 1 for all dose de-escalation patients (1.8 years), the first cycle is 28 days for each individual patient |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | -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. | 30 days after completion of treatment (median time was 67.5 days) |
Not provided
Inclusion Criteria:
Histologically or cytologically confirmed newly diagnosed treatment-naïve metastatic adenocarcinoma of the pancreas with metastatic disease diagnosed no more than 6 weeks prior to enrollment. Patients with advanced pancreatic cancer progressed on 5-FU (or capecitabine) based regimen will be allowed in the expansion cohort.
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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Kian-Huat Lim, M.D., Ph.D. | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36427020 | Derived | Grierson PM, Tan B, Pedersen KS, Park H, Suresh R, Amin MA, Trikalinos NA, Knoerzer D, Kreider B, Reddy A, Liu J, Der CJ, Wang-Gillam A, Lim KH. Phase Ib Study of Ulixertinib Plus Gemcitabine and Nab-Paclitaxel in Patients with Metastatic Pancreatic Adenocarcinoma. Oncologist. 2023 Feb 8;28(2):e115-e123. doi: 10.1093/oncolo/oyac237. | |
| 28939558 | Derived | Germann UA, Furey BF, Markland W, Hoover RR, Aronov AM, Roix JJ, Hale M, Boucher DM, Sorrell DA, Martinez-Botella G, Fitzgibbon M, Shapiro P, Wick MJ, Samadani R, Meshaw K, Groover A, DeCrescenzo G, Namchuk M, Emery CM, Saha S, Welsch DJ. Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22. |
| Label | URL |
|---|---|
| Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine | View source |
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The study opened to participant enrollment on 06/06/2016 and closed to participant enrollment on 08/19/2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine |
|
| FG001 | Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine |
|
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine |
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) of BVD-523 | -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 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. | Posted | Number | mg | Completion of cycle 1 for all dose de-escalation patients (1.8 years), the first cycle is 28 days for each individual patient |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 600 mg BVD-523/Nab-paclitaxel/Gemcitabine |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kian-Huat Lim, M.D., Ph.D. | Washington University School of Medicine | 314-362-6157 | kian-huat.lim@wustl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 7, 2020 | Feb 19, 2021 | Prot_SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
Not provided
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| ID | Term |
|---|---|
| C000618314 | ulixertinib |
| C520255 | 130-nm albumin-bound paclitaxel |
| D000068196 | Albumin-Bound Paclitaxel |
| D013660 | Taxes |
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 |
Not provided
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Not provided
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| Nab-paclitaxel |
| Drug |
|
|
| Gemcitabine | Drug |
|
|
| Tumor biopsy | Procedure |
|
| Response Rate |
| Through completion of treatment (median time was 37.5 days) |
| Biochemical Response of Treatment Regimen | -The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9 | Through completion of treatment (median time was 37.5 days) |
| Time to Tumor Progression (TTP) |
| Up to 2 years |
| Progression-free Survival (PFS) |
| Up to 2 years |
| Overall Survival (OS) | -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. | Up to 2 years |
| BG001 | Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine |
|
|
|
| Secondary | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | -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. | Posted | Count of Participants | Participants | 30 days after completion of treatment (median time was 67.5 days) |
|
|
|
| Secondary | Response Rate |
| 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. | Posted | Count of Participants | Participants | Through completion of treatment (median time was 37.5 days) |
|
|
|
| Secondary | Biochemical Response of Treatment Regimen | -The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9 | -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. | Posted | Count of Participants | Participants | Through completion of treatment (median time was 37.5 days) |
|
|
|
| Secondary | Time to Tumor Progression (TTP) |
| 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. | Posted | Median | Full Range | days | Up to 2 years |
|
|
|
| Secondary | Progression-free Survival (PFS) |
| 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. | Posted | Median | Full Range | days | Up to 2 years |
|
|
|
| Secondary | Overall Survival (OS) | -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. | 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. | Posted | Median | 95% Confidence Interval | months | Up to 2 years |
|
|
|
| 11 |
| 12 |
| 8 |
| 12 |
| 12 |
| 12 |
| EG001 | 450 mg BVD-523/Nab-paclitaxel/Gemcitabine |
| 5 | 6 | 4 | 6 | 6 | 6 |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lower GI hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Death due to disease progression | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Abdominal infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Adult respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hearing impaired | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Taste change | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Chills | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema limb | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema trunk | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Thrush | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Numbness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sweating | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Scalp sun burned | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperhydrosis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blood in stool | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Portal vein thrombosis | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D004066 |
| Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| 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 |
|