Ulixertinib in Treating Patients with Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders with MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
Description
This phase II Pediatric MATCH trial studies how well ulixertinib works in treating patients with solid tumors that have spread to other places in the body (advanced), non-Hodgkin lymphoma, or histiocytic disorders that have a genetic alteration (mutation) in a signaling pathway called MAPK. A signaling pathway consists of a group of molecules in a cell that control one or more cell functions. Genes in the MAPK pathway are frequently mutated in many types of cancers. Ulixertinib may stop the growth of cancer cells that have mutations in the MAPK pathway.
Eligibility Criteria
Inclusion Criteria
- Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621J based on the presence of an actionable mutation.
- Patients must have a body surface area >= 0.54 m^2 at the time of study enrollment.
- Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG)+ evaluable disease are eligible. Measurable disease in patients with central nervous system (CNS) involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice. * Note: The following do not qualify as measurable disease: ** Malignant fluid collections (e.g., ascites, pleural effusions) ** Bone marrow infiltration except that detected by MIBG scan for neuroblastoma ** Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma ** Elevated tumor markers in plasma or cerebrospinal fluid (CSF) ** Previously radiated lesions that have not demonstrated clear progression post radiation ** Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately. * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. ** >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea). * Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): >= 7 days after the last dose of agent. * Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. * Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. * Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator. * Interleukins, Interferons and Cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors). * Stem cell Infusions (with or without TBI): ** Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion: >= 84 days after infusion and no evidence of GVHD. ** Autologous stem cell infusion including boost infusion: >= 42 days. * Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.). * Radiotherapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial brain metastases (BM) radiation. ** Note: Radiation may not be delivered to “measurable disease” tumor site(s) being used to follow response to subprotocol treatment. * Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy. * Patients must not have received prior exposure to BVD-523FB (ulixertinib) or other ERK inhibitors.
- For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment).
- For patients with solid tumors without known bone marrow involvement: Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
- Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity.
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2, or (within 7 days prior to enrollment).
- A serum creatinine based on age/gender (within 7 days prior to enrollment). * Age 1 to < 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6 * Age 2 to < 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8 * Age 6 to < 10 years, maximum serum creatinine (mg/dL) male 1, female 1 * Age 10 to < 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2 * Age 13 to < 16 years, maximum serum creatinine (mg/dL) male 1.5, female 1.4 * Age >= 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4
- Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment).
- Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L.) (within 7 days prior to enrollment).
- Serum albumin >= 2 g/dL (within 7 days prior to enrollment).
- Shortening fraction of >= 27% by echocardiogram, or (within 7 days prior to enrollment).
- Ejection fraction of >= 50% by gated radionuclide study (within 7 days prior to enrollment).
- QTc interval =< 480 milliseconds (within 7 days prior to enrollment).
- Patients must be able to swallow intact capsules.
- All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria
- Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment and for 3 months after last dose of BVD-523FB (ulixertinib).
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid.
- Patients who are currently receiving another investigational drug are not eligible.
- Patients who are currently receiving other anti-cancer agents are not eligible.
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
- Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
- Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP1A2 and CYP2D6 are not eligible. Strong inhibitors of CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, zafirlukast) should be avoided from 14 days prior to enrollment to the end of the study. Strong inhibitors of CYP2D6 (e.g., bupropion, paroxetine, fluoxetine, quinidine, terbinafine) should also be avoided from 14 days prior to enrollment to the end of the study.
- Patients with known significant ophthalmologic conditions (uncontrolled glaucoma, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible.
- Patients who have an uncontrolled infection are not eligible.
- Patients who have received a prior solid organ transplantation are not eligible.
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
Locations & Contacts
Alabama
Birmingham
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 205-638-9285
Email: oncologyresearch@peds.uab.edu
Arizona
Mesa
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 602-747-9738
Tucson
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: aselegue@email.arizona.edu
Arkansas
Little Rock
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 501-364-7373
California
Downey
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 626-564-3455
Loma Linda
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 909-558-3375
Long Beach
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 562-933-5600
Los Angeles
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 323-361-4110
Madera
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 559-353-3000
Email: Research@valleychildrens.org
Oakland
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 510-428-3324
Email: cgolden@mail.cho.org
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
San Francisco
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-827-3222
Colorado
Aurora
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 303-764-5056
Email: josh.b.gordon@nsmtp.kp.org
Denver
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 303-839-6000
Delaware
Wilmington
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 302-651-6884
Email: dperry@nemours.org
District of Columbia
Washington
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 202-884-2549
Florida
Gainesville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 352-273-8010
Email: cancer-center@ufl.edu
Jacksonville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 904-697-3529
Miami
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-624-2778
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 305-243-2647
Orlando
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 407-303-2090
Email: FH.Cancer.Research@flhosp.org
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 321-843-2584
Email: melissa.leffin@orlandohealth.com
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 407-650-7150
Saint Petersburg
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 727-767-4784
Email: Ashley.Repp@jhmi.edu
Tampa
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 813-356-7168
Email: Katelynn.Colgain@baycare.org
West Palm Beach
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 561-881-2815
Georgia
Atlanta
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 404-785-2025
Email: Leann.Schilling@choa.org
Savannah
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 912-350-7887
Email: clayter1@memorialhealth.com
Idaho
Boise
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 208-381-2774
Email: eslinget@slhs.org
Illinois
Chicago
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
Peoria
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-226-4343
Indiana
Indianapolis
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-248-1199
Iowa
Des Moines
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 515-241-8912
Email: samantha.mallory@unitypoint.org
Iowa City
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-237-1225
Louisiana
New Orleans
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: CHResearch@lcmchealth.org
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 504-703-8712
Email: Gregory.Johnstone@ochsner.org
Maine
Bangor
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 207-973-4274
Maryland
Baltimore
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 410-955-8804
Email: jhcccro@jhmi.edu
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 410-601-6120
Email: pridgely@lifebridgehealth.org
Massachusetts
Boston
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-442-3324
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-726-5130
Michigan
Ann Arbor
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-865-1125
Minnesota
Minneapolis
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 612-813-5193
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 612-624-2620
Rochester
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 855-776-0015
Mississippi
Jackson
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 601-815-6700
Missouri
Kansas City
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 816-302-6808
Email: rryan@cmh.edu
Saint Louis
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 314-268-4000
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 314-251-7066
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu
Nebraska
Omaha
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 402-955-3949
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 402-559-6941
Email: unmcrsa@unmc.edu
New Jersey
Hackensack
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 201-996-2879
Morristown
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 973-971-5900
New Brunswick
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 732-745-8600ext6163
Email: kcovert@saintpetersuh.com
New York
Buffalo
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-767-9355
Email: askroswell@roswellpark.org
New Hyde Park
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 718-470-3460
New York
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 212-263-4434
Email: prmc.coordinator@nyumc.org
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 212-305-6361
Email: nr2616@cumc.columbia.edu
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 212-746-1848
Rochester
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 585-275-5830
Syracuse
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 315-464-5476
North Carolina
Asheville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 828-213-2539
Email: Karen.Smith3@HCAHealthcare.com
Charlotte
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-804-9376
Durham
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-275-3853
Ohio
Cincinnati
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 513-636-2799
Email: cancer@cchmc.org
Columbus
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 614-072-2657
Email: amy.yekisa@nationwidechildrens.org
Dayton
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-228-4055
Toledo
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 419-824-1842
Oklahoma
Oklahoma City
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu
Oregon
Portland
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 503-413-2560
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 503-494-1080
Email: trials@ohsu.edu
Pennsylvania
Danville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 570-271-5251
Email: HemonCCTrials@geisinger.edu
Philadelphia
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 267-425-5544
Email: CancerTrials@email.chop.edu
Pittsburgh
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 412-692-8570
Email: jean.tersak@chp.edu
Puerto Rico
San Juan
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 787-727-1000
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 787-474-0333
South Carolina
Greenville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 864-522-2066
Email: kim.williams3@prismahealth.org
Tennessee
Knoxville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 865-541-8266
Memphis
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 866-278-5833
Email: info@stjude.org
Nashville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-811-8480
Texas
Austin
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 512-628-1902
Email: TXAUS-DL-SFCHemonc.research@ascension.org
Dallas
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 972-566-5588
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 214-648-7097
Email: canceranswerline@UTSouthwestern.edu
Fort Worth
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 682-885-2103
Email: CookChildrensResearch@cookchildrens.org
Houston
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 713-798-1354
Email: burton@bcm.edu
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-632-6789
Email: askmdanderson@mdanderson.org
San Antonio
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 210-575-6240
Email: Vinod.GidvaniDiaz@hcahealthcare.com
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 210-450-3800
Email: phoresearchoffice@uthscsa.edu
Utah
Salt Lake City
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 801-585-5270
Vermont
Burlington
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 802-656-8990
Email: rpo@uvm.edu
Virginia
Norfolk
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 757-066-8724
Email: CCBDCresearch@chkd.org
Richmond
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 804-628-1914
Email: klcampbell@vcu.edu
Washington
Seattle
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 866-987-2000
Spokane
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-228-6618
Email: HopeBeginsHere@providence.org
Tacoma
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 253-968-0129
Email: mamcdci@amedd.army.mil
Wisconsin
Madison
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-622-8922
Milwaukee
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 414-955-4727
Email: MACCCTO@mcw.edu
Trial Objectives and Outline
PRIMARY OBJECTIVES:
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with BVD-523FB (ulixertinib) with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the MAPK pathway.
SECONDARY OBJECTIVES:
I. To estimate the progression free survival in pediatric patients treated with BVD-523FB (ulixertinib) with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the MAPK pathway.
II. To obtain information about the tolerability of BVD-523FB (ulixertinib) in children and adolescents with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics of BVD-523FB (ulixertinib) in children and adolescents with relapsed or refractory cancer.
EXPLORATORY OBJECTIVES:
I. To evaluate other biomarkers as predictors of response to BVD-523FB (ulixertinib) and specifically, whether tumors that harbor different mutations or fusions will demonstrate differential response to BVD-523FB (ulixertinib) treatment.
II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
OUTLINE: This is a dose-escalation study.
Patients receive ulixertinib orally (PO) twice daily (BID). Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Trial Phase & Type
Treatment
Lead Organization
Lead Organization
Childrens Oncology Group
Principal Investigator
Kieuhoa Tran Vo