Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
- Conditions
- Ann Arbor Stage III Childhood Non-Hodgkin LymphomaEwing SarcomaAdvanced Malignant Solid NeoplasmEpendymomaHepatoblastomaMalignant GliomaOsteosarcomaPeripheral Primitive Neuroectodermal TumorRecurrent Childhood Central Nervous System NeoplasmMalignant Germ Cell Tumor
- Interventions
- Other: Laboratory Biomarker Analysis
- Registration Number
- NCT03220035
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II Pediatric MATCH trial studies how well vemurafenib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with BRAF V600 mutations that have spread to other places in the body (advanced) and have come back (recurrent) or do not respond to treatment (refractory). Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
- Detailed Description
PRIMARY OBJECTIVE:
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with vemurafenib with advanced solid tumors (including central nervous system \[CNS\] tumors), lymphomas or histiocytic disorders that harbor activating BRAF V600 mutations.
SECONDARY OBJECTIVES:
I. To estimate the progression free survival in pediatric patients treated with vemurafenib with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating BRAF V600 mutations.
II. To obtain information about the tolerability of vemurafenib in children with relapsed or refractory cancer.
EXPLORATORY OBJECTIVE:
I. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
OUTLINE:
Patients receive vemurafenib orally (PO) twice daily (BID) on day 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4
-
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621G based on the presence of a BRAF V600 mutation
-
Patients must have a body surface area >= 0.55 m^2 at enrollment; patients < 0.73 m^2 must follow the dosing nomogram; patients >= 0.73 m^2 at enrollment must follow the dosing nomogram
-
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) positive (+) evaluable disease are eligible; measurable disease in patients with 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 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 absolute neutrophil count [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 total-body irradiation [TBI]):
- Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (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.)
-
Radiation therapy (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 bone marrow (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, iobenguane I-131 [131I-MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
-
Patients must not have received prior exposure to a BRAF inhibitor (e.g. vemurafenib, dabrafenib or encorafenib)
-
-
For patients with solid tumors without known bone marrow involvement:
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- 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 in above criteria (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 a serum creatinine based on age/gender as follows:
- 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
-
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)
-
Serum albumin >= 2 g/dL
-
Corrected QT (QTc) interval =< 480 milliseconds; Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades De Pointes; if possible, alternative agents should be considered; patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available
-
Patients must be able to swallow intact tablets
-
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
- 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 6 months after the last dose of vemurafenib
- 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 moderate to strong inducers or inhibitors of CYP3A4 are not eligible; moderate to 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 inhibitors or inducers of p-glycoprotein (P-gp) or adenosine triphosphate (ATP)-binding cassette, subfamily G, member 2 (ABCG2 [BCRP]) are not eligible
- Patients with known active cutaneous squamous cell carcinoma (includes keratoacanthoma or mixed keratoacanthoma subtype) are not eligible; patients who have fully excised lesions with dermatologic confirmation of absence of disease are eligible
- Patients with low grade glioma patients (World Health Organization [WHO] grades I and II) 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (vemurafenib) Laboratory Biomarker Analysis Patients receive vemurafenib PO BID on day 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Treatment (vemurafenib) Vemurafenib Patients receive vemurafenib PO BID on day 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) From enrollment to the end of treatment, up to 2 years ORR will be defined as complete response + partial response and assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.
- Secondary Outcome Measures
Name Time Method Progress Free Survival (PFS) From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 5 years PFS will be defined as time from the initiation of protocol treatment to the I of any of the following events: disease progression or disease recurrence or death from any cause. Patients with local calls of disease progression (i.e. calls made by the treating institution), will be counted as having had an event, even if the central review does not declare progression. PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
Percentage of Patients Experiencing Grade 3 or Higher Adverse Events From enrollment to 30 days after the end of treatment, up to 2 years Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity.
Trial Locations
- Locations (116)
Children's Healthcare of Atlanta - Arthur M Blank Hospital
🇺🇸Atlanta, Georgia, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Banner Children's at Desert
🇺🇸Mesa, Arizona, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Mission Hospital
🇺🇸Asheville, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
UMC Cancer Center / UMC Health System
🇺🇸Lubbock, Texas, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
University of Vermont and State Agricultural College
🇺🇸Burlington, Vermont, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
San Jorge Children's Hospital
🇵🇷San Juan, Puerto Rico
University Pediatric Hospital
🇵🇷San Juan, Puerto Rico