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

NCT05525273 | Recruiting Phase 2

• 1 other identifier: ver 1-21
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Craniopharyngioma

Keywords

BRAF mutation; Dabrafenib; Trametinib; Neoadjuvant; Postoperative

Outcome Measures

Primary Outcomes (1)

• Tumor response

  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

  1 month to 5 years (sliding timepoints)

Secondary Outcomes (10)

• Response ratio

  1 year after initiation of study treatment

• Response duration

  From time of study drug discontinuation to time of observed increased tumor volume assessed up to 1 year

• Operability after neoadjuvant trial treatment

  1 year after initiation of study treatment

• Progression-free survival 1 year

  1 year

• Progression-free survival 2 years

  2 years

Other Outcomes (5)

• Levels of circulating mutated BRAF

  1 week after initiation of trial treatment

• Levels of circulating mutated BRAF

  2 weeks after initiation of trial treatment

• Levels of circulating mutated BRAF

  6 months after initiation trial treatment

Study Arms (1)

Dabrafenib and trametinib

EXPERIMENTAL

Dabrafenib 75 mg twice daily and trametinib 2 mg once daily

Drug: Oral dabrafenib and trametinib

Interventions

Oral dabrafenib and trametinib DRUG

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

Dabrafenib and trametinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically verified papillary craniopharyngioma.
• BRAF mutated V600E (valine 600 glutamine), verified immunohistochemically and by molecular genetic analysis
• 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.
• Age over 18 years
• Functional status according to ECOG (Eastern Cooperative Oncology Group performance status) 0-2
• 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
• Ability to understand and give informed consent.
• Previous cancer, which does not require current treatment is allowed.
• The patient agrees to use an adequate method to avoid pregnancy.

You may not qualify if:

• Ongoing treatment in another drug study or other experimental treatment.
• Previous treatment with BRAF or MEK inhibitors.
• Hypersensitivity to study drugs.
• 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.
• Women who are pregnant or breastfeeding.
• Previous central serous retinopathy or retinal vein occlusion.
• Surgery within the last 3 weeks.
• For postoperative patients; radiation therapy within the last 3 months.

Sponsors & Collaborators

• Eva Marie Erfurth, MD, PhD: lead
• Novartis: collaborator

Study Sites (1)

Department of Endocrinology

Lund, 22185, Sweden

RECRUITING

MeSH Terms

Conditions

Craniopharyngioma

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Peter Siesjö, MD. PhD.

  Department of Neurosurgery, SUS, Lund Sweden

  STUDY CHAIR

• Sara Kinhult, MD. PhD

  Department of Oncology, SUS, Lund Sweden

  STUDY CHAIR

• Eva Marie Erfurth, MD. PhD

  Department of Endocrinology, SUS, Lund, Sweden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eva Marie Erfurth, MD. PhD.

CONTACT

+4646172363; eva_marie.erfurth@med.lu.se

Sara Kinhult, MD. PhD.

CONTACT

+4646177587; sara.kinhult@skane.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Phase 1, single arm, open label, multicenter.

Study Record Dates

• First Submitted: April 20, 2022
• First Posted: September 1, 2022
• Study Start: September 1, 2023
• Primary Completion (Estimated): September 10, 2027
• Study Completion (Estimated): April 10, 2028
• Last Updated: February 14, 2024

Record last verified: 2024-02

Locations

SE (1)