Status:
TERMINATED
Study of Ulixertinib for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations
Lead Sponsor:
BioMed Valley Discoveries, Inc
Conditions:
Advanced Solid Tumor
BRAF Gene Mutation
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This BVD-523-ABC study builds on the safety and clinical activity experience of previous studies that have evaluated ulixertinib as a novel targeted cancer treatment in cohorts of patients with specif...
Detailed Description
This multi-center, phase II study will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib (BVD-523) in patients with advanced mali...
Eligibility Criteria
Inclusion
- Patients with a locally advanced or metastatic malignancy, that has progressed following systemic therapy for their disease, if available, or for which the patient is not a candidate or refuses.
- Tumors harboring a MEK or atypical BRAF alteration.
- Provide signed and dated informed consent prior to initiation of any study-related procedures that are not considered standard of care (SoC).
- Male or female patients aged ≥18 years.
- Patients must have measurable disease by RECIST version 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
- Adequate renal function \[creatinine ≤1.5 times ULN (upper limit of normal)\] or a glomerular filtration rate (GFR) of ≥50 mL/min (using Cockcroft-Gault).
- Adequate hepatic function \[total bilirubin ≤1.5 times ULN; AST (aspartate transaminase) and ALT (alanine transaminase) ≤3 times ULN or ≤5 times ULN if the elevation is due to liver involvement by tumor\].
- Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x 109 cells/L; absolute neutrophil count ≥1.5 x 109 cells/L).
- Adequate cardiac function: Left ventricular ejection fraction (LVEF) of \>50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and a corrected QT interval (QTc) \<480ms by the Fridericia method (QTcF).
- Contraception - women: Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal (no menstrual cycle for at least 12 consecutive months), or compliant with a medically approved contraceptive regimen during and for 3 months after the last administration of study drug. Abstinence is not considered an adequate contraceptive regimen.
- Contraception - men: Must be surgically sterile, or compliant with a medically approved contraceptive regimen during and for 3 months after the last administration of study drug.
- Willing and able to participate in the trial and comply with all trial requirements.
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational agent may be included after consultation with the medical monitor.
Exclusion
- Gastrointestinal (GI) condition that could impair absorption of study medication (specific cases e.g., remote history of GI surgery, may be enrolled after discussion with the medical monitor) or inability to ingest 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, with no dose change in the previous 4 weeks, can be allowed.
- Having received any cancer-directed therapy (chemotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. Patients previously treated with radiotherapy must have recovered from the acute toxicities associated with such treatment.
- 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 study drug. A minimum of 10 days between termination of the prior investigational drug and administration of study drug is required. In addition, any drug-related toxicity except alopecia should have recovered to Grade 1 or less.
- Prior therapy with any ERK inhibitor (e.g. LY3214996, LTT462).
- Groups 1-4: Prior therapy with any BRAF and/or MEK inhibitor (e.g. encorafenib, dabrafenib, vemurafenib, binimetinib, trametinib, cobimetinib) is excluded. Prior BRAF and/or MEK inhibitor therapy is permitted for Groups 5 and 6.
- For Part B, agents targeting BRAF or MEK kinases and experimental agents are not permitted as physician's choice
- Pregnant or breast-feeding women.
- Any evidence of serious active infections. Patients are allowed to enroll if they have been fever-free for at least 48 hours and are on an active treatment that is not prohibited in Appendix 1 of the protocol.
- Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study (based on the investigator's judgment).
- A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
- Concurrent therapy with any other investigational agent.
- Concurrent therapy with drugs known to be strong inhibitors or inducers of CYP1A2, CYP2D6, and CYP3A4.
Key Trial Info
Start Date :
January 7 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 23 2023
Estimated Enrollment :
104 Patients enrolled
Trial Details
Trial ID
NCT04488003
Start Date
January 7 2021
End Date
May 23 2023
Last Update
June 4 2024
Active Locations (22)
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1
Mayo Clinic
Phoenix, Arizona, United States, 85054
2
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States, 92663
3
Christiana Care Health Services / Helen F. Graham Cancer Center
Newark, Delaware, United States, 19713
4
Johns Hopkins Sibley Memorial Hospital
Washington D.C., District of Columbia, United States, 20016