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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)

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 and have come back or do not respond to treatment. Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Germ Cell (Pediatrics), Miscellaneous, Neuroblastoma (Pediatrics), Pediatric Lymphoma, Pediatric Solid Tumors, Pediatrics, Wilms / Other Kidney (Pediatrics)
Phase II
Both
Mol. targeted/Immunotherapy/Biologics
PLX4032, RO5185426 (Vemurafenib), Vemurafenib
Borinstein, Scott
National
Vanderbilt University
06-26-2018
Treatment
COGAPEC1621G
NCT03220035

Eligibility

12 Months
BOTH
NO
Inclusion Criteria:

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 >= 0.37 m^2 at enrollment while the 120 mg strength tablet supply is available; patients = 0.73 m^2 at enrollment must follow the dosing nomogram

Patients enrolled after the drug supply of the 120 mg strength has been exhausted must have a body surface area >= 0.73 m^2 at enrollment and 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 =
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 == 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 = 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4

Bilirubin (sum of conjugated + unconjugated) =
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =
Serum albumin >= 2 g/dL

Corrected QT (QTc) interval =
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



Exclusion Criteria:

Pregnant or breast-feeding women will not be entered on this study; 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

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