Back to resultsTreatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma (Swecranio)
Primary Purpose
Craniopharyngioma
Status
Recruiting
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Oral dabrafenib and trametinib
Sponsored by
About this trial
This is an interventional treatment trial for Craniopharyngioma focused on measuring BRAF mutation, Dabrafenib, Trametinib, Neoadjuvant, Postoperative
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Ongoing treatment in another drug study or other experimental treatment.
- Previous treatment with BRAF or MEK inhibitors.
- Hypersensitivity to study drugs.
- 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.
- 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.
- Active bleeding; intracranial hemorrhage last 4 weeks before inclusion.
- Thromboembolic disease last 6 months and unstable anticoagulant treatment less than 4 weeks before inclusion.
- Women who are pregnant or breastfeeding.
- Previous central serous retinopathy or retinal vein occlusion.
- Previous uveitis or iritis last 4 weeks before inclusion.
- Surgery within the last 3 weeks.
- For postoperative patients; radiation therapy within the last 3 months.
Sites / Locations
- Department of EndocrinologyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dabrafenib and trametinib
Arm Description
Dabrafenib 75 mg twice daily and trametinib 2 mg once daily
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Response ratio
Response ratio according to RECIST
Response duration
Duration of response for patients treated without subsequent surgery
Operability after neoadjuvant trial treatment
Number of patients which become operable after neoadjuvant treatment
Progression-free survival 1 year
Defined as unchanged or diminished tumor volume
Progression-free survival 2 years
Defined as unchanged or diminished tumor volume
QOL after treatment
Quality of life assessed by EQ5D5L (EuroQual 5 dimensions 5 levels) at 1 year after start of study treatment and compared to baseline
QOL after treatment
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 after treatment
Cognitive status assessed by CNS (central nervous system) Vital Signs 1 year after initiation of treatment and compared to baseline
Opthalmologic status after treatment
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 after treatment
Hypothalamic status assessed as compound measure of pituitary and hypothalamic status 1 year after initiation of treatment and compared to baseline
Full Information
NCT ID
NCT05525273
First Posted
April 20, 2022
Last Updated
April 12, 2023
Sponsor
Eva Marie Erfurth, MD, PhD
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT05525273
Brief Title
Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma
Acronym
Swecranio
Official Title
Neoadjuvant and Postoperative Treatment With Dabrafenib and Trametinib in BRAF Mutated Papillary Craniopharyngioma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 2023 (Anticipated)
Primary Completion Date
September 10, 2027 (Anticipated)
Study Completion Date
April 10, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Eva Marie Erfurth, MD, PhD
Collaborators
Novartis
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Craniopharyngioma
Keywords
BRAF mutation, Dabrafenib, Trametinib, Neoadjuvant, Postoperative
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Phase 1, single arm, open label, multicenter.
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dabrafenib and trametinib
Arm Type
Experimental
Arm Description
Dabrafenib 75 mg twice daily and trametinib 2 mg once daily
Intervention Type
Drug
Intervention Name(s)
Oral dabrafenib and trametinib
Intervention Description
Neoadjuvant or postoperative treatment of patients with verified BRAF mutated papillary craniopharyngioma
Primary Outcome Measure Information:
Title
Tumor response
Description
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
Time Frame
1 month to 5 years (sliding timepoints)
Secondary Outcome Measure Information:
Title
Response ratio
Description
Response ratio according to RECIST
Time Frame
1 year after initiation of study treatment
Title
Response duration
Description
Duration of response for patients treated without subsequent surgery
Time Frame
From time of study drug discontinuation to time of observed increased tumor volume assessed up to 1 year
Title
Operability after neoadjuvant trial treatment
Description
Number of patients which become operable after neoadjuvant treatment
Time Frame
1 year after initiation of study treatment
Title
Progression-free survival 1 year
Description
Defined as unchanged or diminished tumor volume
Time Frame
1 year
Title
Progression-free survival 2 years
Description
Defined as unchanged or diminished tumor volume
Time Frame
2 years
Title
QOL after treatment
Description
Quality of life assessed by EQ5D5L (EuroQual 5 dimensions 5 levels) at 1 year after start of study treatment and compared to baseline
Time Frame
1 year
Title
QOL after treatment
Description
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
Time Frame
1 year
Title
Cognitive status after treatment
Description
Cognitive status assessed by CNS (central nervous system) Vital Signs 1 year after initiation of treatment and compared to baseline
Time Frame
1 year
Title
Opthalmologic status after treatment
Description
Opthalmologic status assessed as compound measure of visual acuity and visual field defects 1 year after initiation of treatment and compared to baseline
Time Frame
1 year
Title
Hypothalamic status after treatment
Description
Hypothalamic status assessed as compound measure of pituitary and hypothalamic status 1 year after initiation of treatment and compared to baseline
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Levels of circulating mutated BRAF
Description
BRAF assessed by plasma analysis and compared to baseline levels
Time Frame
1 week after initiation of trial treatment
Title
Levels of circulating mutated BRAF
Description
BRAF assessed by plasma analysis and compared to baseline levels
Time Frame
2 weeks after initiation of trial treatment
Title
Levels of circulating mutated BRAF
Description
BRAF assessed by plasma analysis and compared to baseline levels
Time Frame
6 months after initiation trial treatment
Title
Levels of circulating mutated BRAF
Description
BRAF assessed by plasma analysis and compared to baseline levels
Time Frame
12 months after initiation trial treatment
Title
Levels of circulating of mutated BRAF
Description
BRAF assessed by plasma analysis and compared to baseline levels
Time Frame
3 months after end of trial treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
Ongoing treatment in another drug study or other experimental treatment.
Previous treatment with BRAF or MEK inhibitors.
Hypersensitivity to study drugs.
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.
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.
Active bleeding; intracranial hemorrhage last 4 weeks before inclusion.
Thromboembolic disease last 6 months and unstable anticoagulant treatment less than 4 weeks before inclusion.
Women who are pregnant or breastfeeding.
Previous central serous retinopathy or retinal vein occlusion.
Previous uveitis or iritis last 4 weeks before inclusion.
Surgery within the last 3 weeks.
For postoperative patients; radiation therapy within the last 3 months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eva Marie Erfurth, MD. PhD.
Phone
+4646172363
Email
eva_marie.erfurth@med.lu.se
First Name & Middle Initial & Last Name or Official Title & Degree
Sara Kinhult, MD. PhD.
Phone
+4646177587
Email
sara.kinhult@skane.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Siesjö, MD. PhD.
Organizational Affiliation
Department of Neurosurgery, SUS, Lund Sweden
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Sara Kinhult, MD. PhD
Organizational Affiliation
Department of Oncology, SUS, Lund Sweden
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Eva Marie Erfurth, MD. PhD
Organizational Affiliation
Department of Endocrinology, SUS, Lund, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Endocrinology
City
Lund
ZIP/Postal Code
22185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Marie Erfurth, MD, PhD
Phone
+4646172363
Email
eva_marie.erfurth@med.lu.se
First Name & Middle Initial & Last Name & Degree
Sara Kinhult, MD, PhD
Phone
+46 46177587
Email
sara.kinhult@skane.se
First Name & Middle Initial & Last Name & Degree
Eva Marie Erfurth, MD, PhD
First Name & Middle Initial & Last Name & Degree
Kinhult Sara, MD, PhD
First Name & Middle Initial & Last Name & Degree
Ekman Bertil, MD, PhD
First Name & Middle Initial & Last Name & Degree
Dalhlqvist Per, MD, PhD
First Name & Middle Initial & Last Name & Degree
Ragnarsson Oscar, MD, PhD
First Name & Middle Initial & Last Name & Degree
Siesjö Peter, MD, PhD
12. IPD Sharing Statement
Learn more about this trial
Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma
We'll reach out to this number within 24 hrs