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Trametinib

Dabrafenib

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Dabrafenib 75 mg twice daily and trametinib 2 mg once daily

Neoadjuvant or postoperative treatment of patients with verified BRAF mutated papillary craniopharyngioma

Oral dabrafenib and trametinib

Eva Marie Erfurth, MD. PhD.

Sara Kinhult, MD. PhD.

Eva Marie Erfurth, MD, PhD

Sara Kinhult, MD, PhD

Kinhult Sara, MD, PhD

Ekman Bertil, MD, PhD

Dalhlqvist Per, MD, PhD

Ragnarsson Oscar, MD, PhD

Siesjö Peter, MD, PhD

Peter Siesjö, MD. PhD.

Sara Kinhult, MD. PhD

Eva Marie Erfurth, MD. PhD

Subjects with papillary craniopharyngioma harboring a BRAF mutation will be treated with a BRAF + MEK inhibitor (dabrafenib + trametinib) after informed consent. Study participants will be administered oral dabrafenib and trametinib until maximal tumor volume reduction assessed by MRI. Progression free survival, cognition, ophthalmologic status, hypothalamic status and quality of life will be assessed 1 year after initiation of study treatment

Background. Papillary craniopharyngioma harbours a BRAF mutation in 90% of cases. Treatment with BRAF + MEK (mitogen activated protein kinase ) inhibitors (dabrafenib + trametinib) may prevent patients from undergoing surgery with a high risk of serious side effects, or provide an additional treatment option when further surgery is not advised.

Study intervention Subjects with newly diagnosed craniopharyngioma where radical surgery is not considered adequate or patients with recurrence of craniopharyngioma where further surgery is not considered possible without serious sequelae will be asked for informed consent Study participants are treated continuously with dabrafenib and trametinib orally, until maximal tumor shrinkage. Evaluation is done by MRI to measure tumor volume, as well as assessment of performance status, quality of life, cognition, ophthalmologic status, performance status and hypothalamic status.

Study type The study is a Phase II, single armed, open label and multicenter study Study drugs are Dabrafenib (Tafinlar) and trametinib (Mekinist) Primary outcome To evaluate tumor response in the form of reduced tumor volume on MRI in patients with papillary craniopharyngioma during treatment with dabrafenib and trametinib.

Secondary outcomes

To evaluate dabrafenib and trametinib treatment for the following aspects:

* response according to RECIST Duration of response for patients treated without subsequent surgery
* how many patients become operable after neoadjuvant treatment
* progression-free survival after 1 and 2 years
* quality of life during and after treatment The effect of treatment on vision, cognition and hypothalamic effects Exploratory outcomes Levels of circulating BRAF Trial population 25 patients Trial duration Participants are treated with the study treatment for at least one year if the treatment is well tolerated, to maximum tumor reduction, or longer according to the investigators´s assessment. Treatment is discontinued in case of progression, unacceptable toxicity or at the request of the patient.

Phase 1, single arm, open label, multicenter.

Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma

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

BRAF assessed by plasma analysis and compared to baseline levels

To evaluate tumor response measured as maximally reduced tumor volume on MRI during treatment with dabrafenib and trametinib. Maximally reduced volume is defined as the time point where no further reduction of tumor volume can be observed

Duration of response for patients treated without subsequent surgery

Number of patients which become operable after neoadjuvant treatment

Defined as unchanged or diminished tumor volume

Quality of life assessed by EQ5D5L (EuroQual 5 dimensions 5 levels) at 1 year after start of study treatment and compared to baseline

Quality of life assessed by EORTC QLQ30 (European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire 30) at 1 year after start of study treatment and compared to baseline

Cognitive status assessed by CNS (central nervous system) Vital Signs 1 year after initiation of treatment and compared to baseline

Opthalmologic status assessed as compound measure of visual acuity and visual field defects 1 year after initiation of treatment and compared to baseline

Hypothalamic status assessed as compound measure of pituitary and hypothalamic status 1 year after initiation of treatment and compared to baseline

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma	NCT05525273	Craniopharyngio...	Oral dabrafenib...	18 Years -	Skane University Hospital
Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma	NCT05525273	Craniopharyngio...	Oral dabrafenib...	18 Years -	Skane University Hospital

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