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

NCT ID: NCT01781429

Last Updated: 2020-03-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-31

Study Completion Date

2018-09-30

Brief Summary

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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.

Detailed Description

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The study is being performed to assess the safety and tolerability of BVD-523

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

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. Patients may also be assessed pharmacodynamic measures in healthy or malignant tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.

Conditions

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Advanced Solid Tumors

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BVD-523

Group Type EXPERIMENTAL

BVD-523

Intervention Type DRUG

Oral, multiple escalating doses, twice daily, for 21 days in each treatment cycle

Interventions

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BVD-523

Oral, multiple escalating doses, twice daily, for 21 days in each treatment cycle

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients with metastatic or advanced-stage malignant tumor. Patients may have received up to 2 prior lines of chemotherapy for their metastatic disease
* ECOG score of 0 or 1
* Predicted life expectancy of ≥ 3 months
* Adequate bone marrow, liver and renal function renal function
* Adequate cardiac function
* 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 the groups below. Patients in groups 1, 2, 4, 5 and 6 may not have been previously treated with BRAF and/or MEK inhibitors

* Group 1: Patients with BRAF mutated cancer, except those with colorectal or non-small cell lung cancers
* Group 2: Patients with BRAF mutated colorectal cancer
* Group 3: Patients with BRAF mutated melanoma who have progressed on, or are refractory to BRAF and/or MEK inhibitors
* Group 4: Patients with NRAS mutated melanoma
* Group 5: Patients with MEK mutated cancer
* Group 6: Patients with BRAF mutated non-small cell lung cancer
* Group 7: Patients with ERK mutated cancer

Exclusion Criteria

* Gastrointestinal 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
* 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.
* 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 or central serous retinopathy
* Concurrent therapy with any other investigational agent
* Concomitant malignancies or previous malignancies with less than 2 years disease-free interval at the time of enrollment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BioMed Valley Discoveries, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UCLA Med-Hematology & Oncology

Los Angeles, California, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Florida Cancer Specialists and Research Group (Sarah Cannon Research Institute)

Sarasota, Florida, United States

Site Status

Massachusetts General Hospital (MGH)

Boston, Massachusetts, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Sarah Cannon Research Institute Hospital at Vanderbilt

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

UT M.D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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Wu J, Liu D, Offin M, Lezcano C, Torrisi JM, Brownstein S, Hyman DM, Gounder MM, Abida W, Drilon A, Harding JJ, Sullivan RJ, Janku F, Welsch D, Varterasian M, Groover A, Li BT, Lacouture ME. Characterization and management of ERK inhibitor associated dermatologic adverse events: analysis from a nonrandomized trial of ulixertinib for advanced cancers. Invest New Drugs. 2021 Jun;39(3):785-795. doi: 10.1007/s10637-020-01035-9. Epub 2021 Jan 3.

Reference Type DERIVED
PMID: 33389388 (View on PubMed)

Mendzelevski B, Ferber G, Janku F, Li BT, Sullivan RJ, Welsch D, Chi W, Jackson J, Weng O, Sager PT. Effect of ulixertinib, a novel ERK1/2 inhibitor, on the QT/QTc interval in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. 2018 Jun;81(6):1129-1141. doi: 10.1007/s00280-018-3564-1. Epub 2018 Mar 30.

Reference Type DERIVED
PMID: 29603015 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28939558 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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BVD-523-01

Identifier Type: OTHER

Identifier Source: secondary_id

BVD-523-01

Identifier Type: -

Identifier Source: org_study_id

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