A Phase 2 interventional study of Laboratory Biomarker Analysis and Vemurafenib in Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma and Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, sponsored by National Cancer Institute (NCI). Completed at 116 sites in 2 countries. Open to participants aged 12 Months to 21 Years. Per ClinicalTrials.gov, last updated 2025-01-27.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
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.
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.
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:
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
Stem cell Infusions (with or without total-body irradiation [TBI]):
For patients with solid tumors without known bone marrow involvement:
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:
Exclusion Criteria:
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.
Other: Laboratory Biomarker Analysis · Drug: Vemurafenib
Correlative studies
Given PO
Also known as: BRAF (V600E) kinase inhibitor RO5185426, BRAF(V600E) Kinase Inhibitor RO5185426, PLX 4032, PLX-4032, PLX4032, RG 7204, RG-7204, RG7204, RO 5185426, RO-5185426, Zelboraf
Objective Response Rate (ORR)
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.
Time frame: From enrollment to the end of treatment, up to 2 years
Progress Free Survival (PFS)
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.
Time frame: 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
Percentage of Patients Experiencing Grade 3 or Higher Adverse Events
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.
Time frame: From enrollment to 30 days after the end of treatment, up to 2 years
Changes in Tumor Genomics
Will explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid. Will be summarized with simple summary statistics and will be descriptive in nature.
Time frame: Baseline up to 4.5 years
| Milestone | Treatment (Vemurafenib) |
|---|---|
| Started | 4 |
| Completed | 0 |
| Not completed | 4 |
| Withdrew: Adverse event | 1 |
| Withdrew: Protocol violation | 1 |
| Withdrew: Progressive disease | 2 |
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.
| percentage of participants | Treatment (Vemurafenib) |
|---|---|
| Objective Response Rate (ORR) | 25 (5.8 to 64.4) |
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 participants | Treatment (Vemurafenib) |
|---|---|
| Progress Free Survival (PFS) | 75 (12.8 to 96.1) |
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.
| percentage of participants | Treatment (Vemurafenib) |
|---|---|
| Percentage of Patients Experiencing Grade 3 or Higher Adverse Events | 75 (19.4 to 99.4) |
Will explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid. Will be summarized with simple summary statistics and will be descriptive in nature.
Results for this outcome have not been posted.
Collected over Adverse Events monitored/assessed from enrollment to 30 days after the end of treatment, up to 2 years. All-Cause Mortality monitored/assessed up to 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Vemurafenib) | 1/4 (25%) | 3/4 (75%) | 3/4 (75%) |
| Event | Treatment (Vemurafenib) |
|---|---|
| Cardiac arrestCardiac disorders | 1/4 |
| HyperglycemiaMetabolism and nutrition disorders | 1/4 |
| Acute kidney injuryRenal and urinary disorders | 1/4 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 1/4 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 1/4 |
| Event | Treatment (Vemurafenib) |
|---|---|
| ConstipationGastrointestinal disorders | 1/4 |
| DiarrheaGastrointestinal disorders | 1/4 |
| FeverGeneral disorders | 1/4 |
| Alanine aminotransferase increasedInvestigations | 1/4 |
| Aspartate aminotransferase increasedInvestigations | 1/4 |
| Lymphocyte count decreasedInvestigations | 1/4 |
| Neutrophil count decreasedInvestigations | 1/4 |
| White blood cell decreasedInvestigations | 1/4 |
| Glucose intoleranceMetabolism and nutrition disorders | 1/4 |
| HyponatremiaMetabolism and nutrition disorders | 1/4 |
| Age, Categorical(Participants) | Treatment (Vemurafenib) |
|---|---|
| <=18 years | 4 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Age, Continuous(years) | Treatment (Vemurafenib) |
|---|---|
| Mean | 11.3 ± 5.7 |
| Sex: Female, Male(Participants) | Treatment (Vemurafenib) |
|---|---|
| Female | 1 |
| Male | 3 |
| Ethnicity (NIH/OMB)(Participants) | Treatment (Vemurafenib) |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 3 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Treatment (Vemurafenib) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 2 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Treatment (Vemurafenib) |
|---|---|
| United States | 4 |
Showing the first 100 of 116 sites across 2 countries.
Documents are hosted by the registry — open the source record to download them.
This study is completed, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
National Cancer Institute (NCI)