Trial Title:
Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma
NCT ID:
NCT05525273
Condition:
Craniopharyngioma
Conditions: Official terms:
Craniopharyngioma
Adamantinoma
Trametinib
Dabrafenib
Conditions: Keywords:
BRAF mutation
Dabrafenib
Trametinib
Neoadjuvant
Postoperative
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Phase 1, single arm, open label, multicenter.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Oral dabrafenib and trametinib
Description:
Neoadjuvant or postoperative treatment of patients with verified BRAF mutated papillary
craniopharyngioma
Arm group label:
Dabrafenib and trametinib
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
Detailed description:
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Endocrinology
Address:
City:
Lund
Zip:
22185
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Eva Marie Erfurth, MD, PhD
Phone:
+4646172363
Email:
eva_marie.erfurth@med.lu.se
Contact backup:
Last name:
Sara Kinhult, MD, PhD
Phone:
+46 46177587
Email:
sara.kinhult@skane.se
Investigator:
Last name:
Eva Marie Erfurth, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Kinhult Sara, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Ekman Bertil, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Dalhlqvist Per, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Ragnarsson Oscar, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Siesjö Peter, MD, PhD
Email:
Sub-Investigator
Start date:
September 1, 2023
Completion date:
April 10, 2028
Lead sponsor:
Agency:
Eva Marie Erfurth, MD, PhD
Agency class:
Other
Collaborator:
Agency:
Novartis
Agency class:
Industry
Source:
Skane University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05525273
