Neoadjuvant and Adjuvant Therapy with Dabrafenib and Trametinib in Patients with Papillary Craniopharyngioma: A Clinical Evaluation of Tumor Volume Reduction

The primary objective of this study is to evaluate the **tumour response** in patients with papillary craniopharyngioma undergoing treatment with dabrafenib and trametinib. This is measured as a reduction in tumour volume on MRI. Assessing tumour response is clinically relevant as it provides insight into the efficacy of the treatment regimen in reducing tumour size, which is crucial for improving patient outcomes and potentially reducing the need for surgical intervention.

Secondary objectives include evaluating the treatment with dabrafenib and trametinib for several aspects: - Response according to RECIST criteria - Duration of response for patients treated without subsequent surgery - Number of patients that 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 function

The clinical trial involves participants diagnosed with **papillary craniopharyngioma**, a rare type of brain tumor. The study population includes both male and female subjects, aged 18 years and older, with a performance status according to ECOG of 0-2, indicating they are fully active or capable of carrying out light work. Participants must have histologically verified papillary craniopharyngioma with a BRAF V600E mutation, confirmed through immunohistochemistry and sequencing. The trial is open to individuals with newly diagnosed tumors or those experiencing a recurrence after previous surgery, where further surgical intervention would result in serious or permanent sequelae. All participants are required to have adequate organ function. The sponsor has not provided information regarding the total number of participants. The trial does not include vulnerable populations, and no specific lifestyle considerations such as diet or physical activity are mentioned as part of the selection criteria.

The clinical trial is designed to evaluate the efficacy of **dabrafenib** and **trametinib** in patients with **papillary craniopharyngioma**. This is a randomized, double-blind, controlled trial with a primary objective to assess tumor response as measured by a reduction in tumor volume on MRI. The trial is categorized as a small phase 2 trial for a rare tumor and is not considered low intervention. The trial is expected to commence recruitment on January 1, 2024, and conclude by December 31, 2029, with an estimated duration of 12 months for each participant's involvement.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically verified papillary craniopharyngioma, BRAF V600E mutation, and adequate organ function. The trial will include follow-up visits to monitor treatment response and safety, with assessments conducted according to RECIST criteria, progression-free survival, and quality of life metrics. The end-of-study visit will evaluate the overall treatment outcomes and any long-term effects on vision, cognition, and hypothalamic function.

Participants will be administered **trametinib** in the form of film-coated tablets and **dabrafenib** as hard capsules, both taken orally. The maximum daily doses are 2 mg for **trametinib** and 300 mg for **dabrafenib**, with a maximum treatment period of 12 months. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The trial aims to provide insights into the potential for these targeted cancer therapies to improve operability and survival outcomes in this patient population.

The clinical trial involves the administration of **TRAMETINIB**, a targeted cancer therapy, in the form of a **film-coated tablet**. The active substance, trametinib, is of chemical origin. The medication is administered **orally** with a maximum daily dose of **2 mg**. The total dose over the treatment period can reach up to **730 mg**. The treatment duration is set for a maximum of **12 months**. Compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen.

Additionally, the trial includes the use of **DABRAFENIB**, another targeted cancer therapy, provided as a **hard capsule**. The active substance, dabrafenib, is also of chemical origin. This medication is administered **orally** with a maximum daily dose of **300 mg**. The total dose over the treatment period can reach up to **109,500 mg**. Similar to trametinib, the treatment duration for dabrafenib is also set for a maximum of **12 months**. Participant compliance is closely monitored to ensure proper adherence to the dosing schedule.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this study. The primary objective of the trial is to evaluate the tumor response, specifically the reduction in tumor volume on MRI, in patients with **papillary craniopharyngioma** undergoing treatment with dabrafenib and trametinib.

Efficacy in the clinical trial for the treatment of **papillary craniopharyngioma** with dabrafenib and trametinib will be assessed primarily by evaluating the reduction in tumor volume as measured by MRI. This primary endpoint aims to determine the tumor response in patients undergoing treatment. Secondary endpoints include assessing the response according to RECIST criteria, the duration of response in patients treated without subsequent surgery, the number of patients who become operable after neoadjuvant treatment, progression-free survival at 1 and 2 years, and the quality of life during and after treatment. Additionally, the effect of treatment on vision, cognition, and hypothalamic function will be evaluated.

The trial will utilize MRI scans to measure tumor volume, and the response will be evaluated using the RECIST criteria, which is a standardized set of rules for assessing changes in tumor size. The schedule for these assessments will be aligned with the treatment protocol, although specific timepoints are not detailed in the provided data. The trial is designed to provide comprehensive insights into the efficacy of the treatment regimen, focusing on both clinical outcomes and patient quality of life.