Treatment for BRAF mutated papillary craniopharyngioma

Neoadjuvant and Postoperative Treatment With Dabrafenib and Trametinib in BRAF Mutated Papillary Craniopharyngioma

This study is testing if a combination of two medications can help shrink tumors in patients with a specific type of brain tumor before they have surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Skane University Hospital (Academic / other)
• Drugs / interventions: radiation, trametinib
• Locations: 1 site (Lund)
• Trial ID: NCT05525273 on ClinicalTrials.gov

What this trial studies

This clinical trial focuses on patients with papillary craniopharyngioma that have a BRAF mutation. Participants will receive a combination of oral dabrafenib and trametinib to reduce tumor volume before considering surgery. The treatment will continue until maximal tumor shrinkage is observed, as assessed by MRI. The study will also evaluate various health outcomes, including cognitive function and quality of life, one year after treatment initiation.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with histologically confirmed papillary craniopharyngioma harboring a BRAF V600E mutation and for whom surgery is not a viable option.

Not a fit: Patients with craniopharyngioma that do not have the BRAF mutation or those who can undergo radical surgery without significant risks may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a less invasive option for patients with BRAF mutated papillary craniopharyngioma, potentially avoiding high-risk surgeries.

How similar studies have performed: Other studies have shown promise in using BRAF and MEK inhibitors for similar conditions, indicating a potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Histologically verified papillary craniopharyngioma.
2. BRAF mutated V600E (valine 600 glutamine), verified immunohistochemically and by molecular genetic analysis
3. Newly diagnosed tumor, or recurrence after previous surgery, where surgery is not considered to be able to be performed radically without the risk of serious or permanent sequelae.
4. Age over 18 years
5. Functional status according to ECOG (Eastern Cooperative Oncology Group performance status) 0-2
6. Adequate organ function:

   neutrophils\> 1.5 x 109 platelets\> 100 x 109 creatinine \<1.5 x ULN (upper limit of normal) or creatinine clearance \<45 ml / min bilirubin \<1.5 x ULN ASAT (aspartate aminotransferase) / ALAT (alanine aminotransferase) \<2.5 x ULN
7. Ability to understand and give informed consent.
8. Previous cancer, which does not require current treatment is allowed.
9. The patient agrees to use an adequate method to avoid pregnancy.

Exclusion Criteria:

1. Ongoing treatment in another drug study or other experimental treatment.
2. Previous treatment with BRAF or MEK inhibitors.
3. Hypersensitivity to study drugs.
4. Ongoing treatment with non-authorized drugs, (strong inducers of CYP2C8 or CYP3A4). If the patient is on unauthorized drugs, they must be discontinued at least 14 days before inclusion.
5. Known cardiovascular disease where treatment with MEK inhibitors is considered inappropriate, eg severe heart failure, prolongation of QT time, uncontrolled arrhythmia, recent (\<6 months) cardiac infarction, uncontrolled hypertension.
6. Active bleeding; intracranial hemorrhage last 4 weeks before inclusion.
7. Thromboembolic disease last 6 months and unstable anticoagulant treatment less than 4 weeks before inclusion.
8. Women who are pregnant or breastfeeding.
9. Previous central serous retinopathy or retinal vein occlusion.
10. Previous uveitis or iritis last 4 weeks before inclusion.
11. Surgery within the last 3 weeks.
12. For postoperative patients; radiation therapy within the last 3 months.

Where this trial is running

Lund

• Department of Endocrinology — Lund, Sweden (Recruiting)

Study contacts

• Principal investigator: Eva Marie Erfurth, MD. PhD — Department of Endocrinology, SUS, Lund, Sweden
• Study coordinator: Eva Marie Erfurth, MD. PhD.

Conditions Craniopharyngioma; BRAF mutation; Dabrafenib; Trametinib; Neoadjuvant; Postoperative