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Tests treatment safety and results for BRAF V600E Mutation
Official title A Trial to Evaluate CSF ctDNA and Safety of Plixorafenib Alone or With Retifanlimab in Patients With BRAF-altered Glioma
ClinicalTrials.gov ID: NCT06610682
What this study is testing
What is Plixorafenib?
Plixorafenib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for braf v600e mutation.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The investigators will evaluate the sensitivity of ctDNA from plasma and CSF at baseline (defined as C1D1) and over time in response to treatment with plixorafenib alone or in combination with retifanlimab in patients with BRAF-V600E mutant glioma refractory to prior therapies.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Inclusion Arm A Only:
- Patient must have received prior BRAF and/or MEK inhibitor therapy.
- Prior RAF dimer disruptor or pan-RAF inhibitor not allowed
- Prior immunotherapy allowed
- The following intervals from previous treatments should have elapsed prior to enrollment: a. BRAFi/MEKi should be stopped 2 weeks prior to surgery
You likely can't join if
- Exclusion Arm A Only:
- Prior RAF dimer disruptor or pan-RAF inhibitor. Exclusion Arm B Only:
- Prior immunotherapy (of note prior RAF dimer-disruptor or pan-RAF inhibitor is allowed).
- Known history of clinically significant autoimmune disease that, in the opinion of the investigator, may be exacerbated by immune checkpoint blockade...
- Daily systemic steroids \> 4mg daily dexamethasone or equivalent.
- Have received a live vaccine within 28 days before the planned start of study treatment. Exclusion Both Arms:
See the full eligibility criteria
Who can join
- Inclusion Arm A Only:
- Patient must have received prior BRAF and/or MEK inhibitor therapy.
- Prior RAF dimer disruptor or pan-RAF inhibitor not allowed
- Prior immunotherapy allowed
- The following intervals from previous treatments should have elapsed prior to enrollment: a. BRAFi/MEKi should be stopped 2 weeks prior to surgery
- Patients must be maintained on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to screening MRI. No maximum dose. Topical and inhaled steroid treatment is allowed. Inclusion...
- Patient must have received prior BRAF and/or MEK inhibitor therapy.
- Prior RAF dimer disruptor or pan-RAF inhibitor allowed,
- Prior immunotherapy not allowed (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathway).
- The following intervals from previous treatments should have elapsed prior to first infusion: a. BRAFi/MEKi should be stopped 7 days prior to first retifanlimab infusion and at least 2 weeks prior to surgery.
- Patients must be maintained on a stable (\<4mg daily dexamethasone) or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to screening MRI. Topical and inhaled steroid treatment is...
- Histologic diagnosis of a primary CNS tumor with documented BRAF-V600E mutation by a CLIA approved DNA or RNA-based sequencing test (NGS or RNAseq). Immunohistochemistry alone is insufficient.
- Karnofsky performance status ≥ 70.
- Patient is 18 years of age or older.
- Measurable disease by RANO 2.0 criteria on screening MRI. Leptomeningeal disease allowed.
- Willing to submit archival tumor sample if available.
- The following intervals from previous treatments should have elapsed prior to either day of surgery (for Arm A) or first infusion of Retifanlimab (for Arm B):
- 12 weeks from the completion of radiation.
- 8 weeks from an anti-VEGF therapy
- 4 weeks from a nitrosourea chemotherapy
- 2 weeks or 5 half-lives from any investigational (not FDA-approved) agents or FDA-approved non-nitrosourea chemotherapy (whichever is shorter)
- Patients must have the following organ and marrow function:
- Absolute neutrophil count \>1,000/mcL
- Platelets \>100,000/mcL
- Hemoglobin \> 9 g/dL
- Total bilirubin \ 1.5 × ULN with direct bilirubin \< 1.5 × ULN;
- AST (SGOT) and ALT (SGPT) \< 2.5 x institutional ULN
- PT or PTT \< 1.5 x institutional ULN
- Creatinine ≤ 1.5 x institutional ULN OR
- Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
- Patient must be able to provide written informed consent.
- All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline except for
- Alopecia (Grade ≤2)
- Sensory neuropathy (Grade ≤2)
- Lymphopenia (Grade \<2)
- Other adverse events that have resolved to Grade ≤2 that, according to the clinical judgment of the investigator, do not constitute a safety risk to the participant.
- Ability to swallow and retain orally administered medications, including a liquid suspension.
- Female participants of childbearing potential (defined as all females who have experienced menarche and who are not postmenopausal or surgically sterile) must have a negative serum pregnancy test prior to study start...
- Male participants must also be documented to be surgically sterile or agree to use adequate contraception and not to donate sperm from screening until 30 days after the last dose of plixorafenib or 120 days after last...
- Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with other malignancies must be...
- Life expectancy equal or greater than six months.
What rules you out
- Exclusion Arm A Only:
- Prior RAF dimer disruptor or pan-RAF inhibitor. Exclusion Arm B Only:
- Prior immunotherapy (of note prior RAF dimer-disruptor or pan-RAF inhibitor is allowed).
- Known history of clinically significant autoimmune disease that, in the opinion of the investigator, may be exacerbated by immune checkpoint blockade (e.g., multiple sclerosis, systemic lupus erythematosus, inflammatory...
- Daily systemic steroids \> 4mg daily dexamethasone or equivalent.
- Have received a live vaccine within 28 days before the planned start of study treatment. Exclusion Both Arms:
- Current use of any other standard or investigational agents (excepting tumor treating fields).
- Known co-occurring NF1 and/or RAS-related alteration known to cause resistance.
- Known hypersensitivity to plixorafenib, retifanlimab or to excipients.
- Current use of a prohibited medication (including herbal medications, supplements, or foods), as described in Section 5.6, or use of a prohibited medication ≤ 7 days prior to first infusion of retifanlimab.
- Impairment in gastrointestinal function or disease that may significantly alter the absorption of oral plixorafenib (such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small...
- Clinically significant cardiovascular disease including, but not limited to the following:
- History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary artery bypass grafting, coronary angioplasty or stenting ≤ 180 days prior to start date;
- Congestive heart failure requiring treatment (New York Heart Association Grade \> 2);
- History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
- QTcF interval ≥ 480 ms.
- History of recent (≤ 90 days) thromboembolic or cerebrovascular event such as transient ischemic attack, cerebrovascular accident, or hemodynamically significant (massive or sub-massive) deep vein thrombosis or...
- Known history of any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus. people with previously treated viral hepatitis and undetectable virus may be...
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible.
- Pregnant women are excluded from this study because the effects of plixorafenib or retifanlimab on a fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to...
- Contraindication to ventricular reservoir placement or biospecimen collection.
- Current use of strong inhibitors or inducers of CYP3A.
The study team makes the final eligibility decision.
Where it's taking place
- Baltimore, Maryland, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Baltimore, Maryland, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.