Trial Title:
Ulixertinib in People With Histiocytic Neoplasms
NCT ID:
NCT06411821
Condition:
Histiocytic Neoplasms
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Ulixertinib (BVD-523)
23-282
Mitogen-activated protein kinase
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Multicenter phase 2 trial evaluating the efficacy and safety of monotherapy ulixertinib,
an oral selective extracellular signalregulated kinase (ERK) inhibitor, for patients with
histiocytic neoplasms:
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ulixertinib
Description:
300 mg twice daily, for every 28-day cycle.
Arm group label:
Mitogen-activated protein kinase (MAPK) pathway mutation (primary cohort)
Arm group label:
No Mitogen-activated protein kinase (MAPK) pathway mutation identified (exploratory cohort)
Other name:
BVD-523
Summary:
The researchers are doing this study is to find out whether ulixertinib is an effective
and safe treatment for people with histiocytic neoplasms.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically confirmed histiocytic neoplasm or histologic findings consistent with
histiocytic neoplasm with confirmatory radiologic or molecular findings. Pathologic
examination can be performed at any of the enrolling institutions. This
qualification is made because it is well known that biopsies of histiocytic
neoplasms are variable and do not always demonstrate "typical" morphologic
appearance with all of the classically described elements. As a result, histiocytic
neoplasms are not exclusively pathologic diagnoses-rather, they are interpretations
of histologic findings in a clinical and radiologic context. These criteria were
applied in NCT02649972 and will be applied in this trial
- Identified mutation in MAPK pathway genes, including but not limited to ARAF, BRAF,
RAF1, NRAS, KRAS, MAP2K1, MAP2K2, and NF1 (primary cohort). Tumor mutation may be
identified by tumor sequencing or cfDNA-based sequencing. Concordance between cfDNA
and tumor sequencing for BRAFV600E and non-BRAF mutations in histiocytic neoplasms
has been documented by our group and others
- Measurable disease according to PRC, confirmed by an investigator radiologist
- Age (a) ≥18 years prior to interim safety and efficacy analyses or (b) ≥12 years
following the interim safety and efficacy analyses
- The histiocytic neoplasm must be (a) disease that is recurrent/refractory/persistent
despite local therapies, chemotherapy, immunosuppression, or BRAF/MEK inhibitors OR
(b) multisystem disease OR (c) single-system disease that is causing end-organ
dysfunction and is unlikely to benefit from local or conventional (chemotherapy or
immunosuppressive) therapies on the basis of evidence-based guidelines (e.g.
symptomatic neurologic-only LCH)
- Prior treatment (chemotherapy, BRAF inhibitor, or MEK inhibitor) is required and the
patient must have (a) progressive disease or persistent disease (i.e. having disease
measurable by PRC) or (b) intolerance or contraindication to chemotherapy, BRAF
inhibition, or MEK inhibition.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (age ≥ 16) or
Lansky 50-100 (age 12-15)
- Adequate renal function (according to the Cockcroft-Gault equation; creatinine ≤1.5
times upper limit of normal [ULN] or a glomerular filtration rate of ≥50 mL/min)
- Pediatric patients (<18 years old) must have a creatinine clearance or
radioisotope GFR ≥ 70 mL/min/1.73 m^2 or serum creatinine based on age/gender
as follows:
- < 13 years- 1.2 (Male),1.2 (Female)
- 13 to < 16 years- 1.5 (Male), 1.4 (Female)
°≥ 16 years- 1.7 (Male), 1.4 (Female)
- The threshold creatinine values in this Table were derived from the Schwartz
formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing
child length and stature data published by the CDC.
- Patients with renal impairment deemed the direct result of disease and
therefore amenable to improvement with Ulixertinib treatment may be enrolled at
the discretion of the treating investigator
- Adequate hepatic function (total bilirubin ≤1.5 times ULN, aspartate transaminase
[AST] and- alanine transaminase [ALT] ≤3 times ULN or ≤5 times ULN if attributable
to liver involvement by tumor). Patients with hepatic impairment deemed the direct
result of disease and therefore amenable to improvement with Ulixertinib treatment
may be enrolled at the discretion of the treating investigator.
- Adequate bone marrow function (hemoglobin ≥9.0 g/dL, platelets ≥100 x 10^9 cells/L,
absolute neutrophil count ≥1.5 x 10^9 cells/L). Patients with cytopenias deemed the
direct result of disease and therefore amenable to improvement with Ulixertinib
treatment may be enrolled at the discretion of the treating investigator.
- Adequate cardiac function
- Left ventricular ejection fraction >50% as assessed by multi-gated acquisition
or ultrasound or echocardiography and
- Corrected QT interval (QTc) <480 ms according to the Fridericia method (QTcF)
- Contraception
- For women: a negative pregnancy test for those 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 treatment period
- For men: must be surgically sterile or compliant with a medically approved
contraceptive regimen during and for 3 months after the treatment period
- For patients aged <18 years who are not sexually active: abstinence is an
acceptable form of contraception. The reliability of sexual abstinence needs to
be evaluated in relation to the duration of the study and the preferred and
usual lifestyle of the participant.
- 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 at the discretion of the site PI
Exclusion Criteria:
- Uncontrolled or severe intercurrent medical condition
- Receipt of any histiocytic neoplasm-directed therapy (chemotherapy, targeted
therapy, biologic) within 28 days or 5 half-lives (whichever is shorter) before the
first dose of ulixertinib. Patients previously treated with radiotherapy must have
recovered from acute toxicities associated with such treatment
- Histiocytic neoplasm mandated for observation-only or first-line local therapy per
established guidelines. Examples would include asymptomatic nodal RDD, asymptomatic
osseous ECD, or limited cutaneous LCH
- Major surgery within 4 weeks of the first dose of ulixertinib
- Pregnant, lactating, or breast-feeding (for women)
- Any evidence of serious active infections. Patients are allowed to enroll if they
have been fever free for at least 48 h
- History or current evidence of risk of retinal vein occlusion or central serous
retinopathy. Examples of risk factors to be considered would include uncontrolled
ocular hypertension or history of hyperviscosity.
- Concurrent therapy with drugs known to be strong inhibitors or inducers of CYP1A2,
CYP2D6, and CYP3A4
- Concurrent therapy with p-glycoprotein inhibitors and sensitive substrates of
CYP1A2, CYP2B6, CYP2C8, and CYP3A4/5 with narrow therapeutic indices
- Inability to swallow oral medications
- Prior stomach or duodenal resection that, in the opinion of the site PI, would
affect the breakdown and absorption of the study medications. Patients with a
feeding tube will also be excluded, as ulixertinib tablets cannot be taken broken,
cracked or otherwise not intact. Note: ulixertinib is primarily absorbed in the
duodenum, and therefore the potential inclusion of a patient with any prior stomach
or duodenal resection should be discussed with the MSK PI
- Concurrent therapy with any investigational agent
- Any use of an investigational drug within 28 days or 5 half-lives (whichever is
shorter). In addition, any drug toxicities should have recovered to grade 1 or less
before start of the trial medication
Gender:
All
Minimum age:
12 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Basking Ridge (Consent Only)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eli Diamond, MD
Phone:
212-610-0243
Facility:
Name:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eli Diamond, MD
Phone:
212-610-0243
Facility:
Name:
Memorial Sloan Kettering Bergen (Consent Only)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eli Diamond, MD
Phone:
212-610-0243
Facility:
Name:
Memorial Sloan Kettering Suffolk-Commack (Consent Only)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eli Diamond, MD
Phone:
212-610-0243
Facility:
Name:
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eli Diamond, MD
Phone:
212-610-0243
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eli Diamond, MD
Phone:
212-639-7576
Contact backup:
Last name:
Rona Yaeger, MD
Phone:
646-888-5109
Investigator:
Last name:
Eli Diamond, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Nassau (Consent Only)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eli Diamond, MD
Phone:
212-610-0243
Start date:
May 7, 2024
Completion date:
May 2027
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
BioMed Valley Discoveries, Inc
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06411821
http://www.mskcc.org/mskcc/html/44.cfm
