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Tests treatment safety and results for Cancer Harboring BRAF Alterations
Official title A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations
ClinicalTrials.gov ID: NCT05503797
What this study is testing
What is Plixorafenib?
Plixorafenib is an investigational medicine, given as a pill taken by mouth, being studied as a potential treatment for cancer harboring braf alterations.
Also referred to as FORE8394, PLX8394.
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 objective of this Master Protocol is to evaluate the efficacy and safety of plixorafenib in participants with locally advanced or metastatic solid tumors, or recurrent or progressive primary central nervous system (CNS) tumors harboring BRAF fusions, or in participants with rare BRAF V600-mutated solid tumors, melanoma, thyroid, or recurrent primary CNS tumors.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 10 and older
You may be able to join if
- Subprotocol A:
- Male and female, ≥10 years of age, and weighing ≥30 kg.
- Histologic diagnosis of a solid tumor or primary CNS tumor.
- Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome)...
- Have an archival tissue sample available meeting protocol requirements.
You likely can't join if
- Subprotocol A:
- Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations for advanced unresectable or metastatic disease.
- Prior treatment with a MEK inhibitor.
- Tyrosine kinase inhibitor(s) and/or targeted therapies are allowed (other than BRAF/MAPK pathway inhibitors per Exclusion Criteria 3 and 4) and will...
- Malignancy with co-occurring activating RAS mutation(s) at any time.
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
See the full eligibility criteria
Who can join
- Subprotocol A:
- Male and female, ≥10 years of age, and weighing ≥30 kg.
- Histologic diagnosis of a solid tumor or primary CNS tumor.
- Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome) sequencing.
- Have an archival tissue sample available meeting protocol requirements.
- Consent to provide scan(s) prior to baseline to assess change in tumor trajectory.
- Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.
- All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline. Subprotocol B:
- Male and female, ≥10 years of age, and weighing ≥30 kg.
- Histological diagnosis of a primary CNS tumor, including but not limited to the following:
- Adults (≥18 years) with Grade 1-4 glioma or glioneuronal tumor (including glioblastoma, anaplastic astrocytoma, high grade astrocytoma with piloid features, pilocytic astrocytoma, gliosarcoma, anaplastic pleomorphic...
- Pediatric patients (10-17 years of age) with a Grade 3 or 4 glioma or glioneuronal tumor, including those with a prior, histologically confirmed, diagnosis of a low-grade glioma or glioneuronal tumor and now have...
- Participants must have unresectable, locally advanced or metastatic disease that: i. Had prior treatment with radiotherapy and/or first-line chemotherapy or concurrent chemoradiation therapy OR
- Note: Participants who have a WHO Grade 3 or 4 glioma for whom chemotherapy and/or radiotherapy is not considered standard of care may remain eligible for the study. ii. Is intolerant to available therapies OR iii. The...
- Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test at CLIA or CLIA-equivalent laboratory approved by sponsor or sponsor-designated central test.
- An archival tissue sample available meeting protocol requirements, or fresh biopsy is required if the archival sample is not available for retrospective confirmation test.
- Consent to provide scan(s) prior to baseline to assess change in tumor trajectory.
- Measurable disease based upon specified response criteria, as determined by the radiographic BICR.
- All adverse events related to prior therapies (eg, chemotherapy, radiotherapy, surgery) must have resolved to Grade 1 or baseline.
- Participants who are receiving corticosteroid treatment must be on a stable or decreasing dose of ≤8 mg/day of dexamethasone or equivalent corticosteroid treatment for 7 days prior to first dose of study treatments...
- Male and female, ≥10 years of age, and weighing ≥30 kg.
- Histologic diagnosis of a rare BRAF V600E-mutated solid tumor that is unresectable, locally advanced or metastatic.
- Measurable disease on CT, MRI, or physical exam
- Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test.
- Have an archival tissue sample available meeting protocol requirements.
- Consent to provide scan(s) prior to baseline to assess change in tumor trajectory
- Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate. Subprotocol D:
- Male and female, 18 - 65 years of age.
- Histologic diagnosis of a solid tumor harboring a BRAF V600E mutation and not eligible for other subprotocols.
- Measurable disease on CT, MRI, or physical exam.
- Evidence of BRAF V600E mutation in tumor and/or blood detected by genomic tests.
- Consent to provide a tumor biopsy.
- Willingness to comply with the ECG substudy procedures.
- All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline.
What rules you out
- Subprotocol A:
- Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations for advanced unresectable or metastatic disease.
- Prior treatment with a MEK inhibitor.
- Tyrosine kinase inhibitor(s) and/or targeted therapies are allowed (other than BRAF/MAPK pathway inhibitors per Exclusion Criteria 3 and 4) and will be restricted to no more than the number of lines of therapy that are...
- Malignancy with co-occurring activating RAS mutation(s) at any time.
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
- HIV infection with exceptions; discuss with treating physician.
- Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral plixorafenib or cobicistat (such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea...
- Grade ≥2 changes in AST, ALT, GGT, or bilirubin attributed to prior immune checkpoint inhibitor treatment are exclusionary, even if resolved. Subprotocol B:
- Prior treatment with BRAF, ERK, and/or MEK inhibitor(s).
- Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations.
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
- Active infection requiring systemic therapy.
- HIV infection with exceptions; discuss with treating physician.
- Have impairment of GI function or GI disease that may significantly alter the absorption of oral plixorafenib (such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel...
- Grade ≥ 2 changes in AST, ALT, gamma-glutamyl transaminase (GGT), or bilirubin attributed to prior immune checkpoint inhibitor treatment are exclusionary, even if resolved. Subprotocol C:
- Diagnosis of colorectal adenocarcinoma or pancreatic ductal adenocarcinoma (neuroendocrine or acinar tumors are eligible).
- Diagnosis of BRAF V600E-mutated cutaneous melanoma, papillary thyroid cancer, or NSCLC.
- Participant has CNS metastases.
- Prior treatment with BRAF, ERK, and/or MEK inhibitor(s), unless otherwise specified for specific tumor types (i.e. low grade serous or borderline ovarian cancer).
- Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations.
- Participants with prostate, breast, or gynecologic cancers with known activating mutations that lead to constitutive hormone receptor activation (AR-V7, ESR1).
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
- Active infection requiring systemic therapy.
- HIV infection with exceptions; discuss with treating physician. Subprotocol D:
- Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations or other co-occurring driver mutations.
- Participant has a non-CNS solid tumor with CNS metastases.
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
- Active infection requiring systemic therapy.
- HIV infection with exceptions; discuss with treating physician.
- Use or anticipate the need for medications with known risk for QT-prolonging potential and Torsades de Pointes.
- History of acute or chronic cardiovascular disease or surgery, hypertension, with systolic blood pressure \>160mm HG, history of QTc abnormalities, or clinical significantly ECG abnormalities.
The study team makes the final eligibility decision.
Where it's taking place
- Beverly Hills, California, United States
- San Francisco, California, United States
- Westwood, Los Angeles, California, United States
- Norwalk, Connecticut, United States
- Miami, Florida, United States
- Baltimore, Maryland, United States
- Rockville, Maryland, United States
- Boston, Massachusetts, United States
- Duluth, Minnesota, United States
- Saint Joseph, Missouri, United States
- Omaha, Nebraska, United States
- Summit, New Jersey, United States
- New York, New York, United States
- Winston-Salem, North Carolina, United States
- Columbus, Ohio, United States
- Maumee, Ohio, United States
- Toledo, Ohio, United States
- Philadelphia, Pennsylvania, United States
- Providence, Rhode Island, United States
- Nashville, Tennessee, United States
+ 43 more site(s).
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, 10 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Beverly Hills, California, United States; San Francisco, California, United States; Westwood, Los Angeles, California, United States; Norwalk, Connecticut, United States; Miami, Florida, United States; Baltimore, Maryland, United States and 57 more location(s). 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.