CraniopharyngiomaPhase 2SwecranioNCT05525273
Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma
A Phase 2 study testing Oral dabrafenib and trametinib in people with Craniopharyngioma, run by Eva Marie Erfurth, MD, PhD at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Craniopharyngioma
- What is being tested?
- Oral dabrafenib and trametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteSweden
- Study dates
- 1 Sep 2023to 10 Apr 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site, 1 recruiting
- Recruiting
Department of Endocrinology
Lund, 22185
Eva Marie Erfurth, MD, PhD, +4646172363, eva_marie.erfurth@med.lu.se
Sara Kinhult, MD, PhD, +46 46177587, sara.kinhult@skane.se
About this study
Official title: Neoadjuvant and Postoperative Treatment With Dabrafenib and Trametinib in BRAF Mutated Papillary Craniopharyngioma
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
Read the 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.
- Conditions
- Craniopharyngioma
- Being tested
- Oral dabrafenib and trametinib
- Keywords
- BRAF mutation, Dabrafenib, Trametinib, Neoadjuvant, Postoperative
- Medical subject headings
- Craniopharyngioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral dabrafenib and trametinibDrug
Neoadjuvant or postoperative treatment of patients with verified BRAF mutated papillary craniopharyngioma
| Study group | Role | What they receive |
|---|---|---|
| Dabrafenib and trametinib | Experimental | Dabrafenib 75 mg twice daily and trametinib 2 mg once daily Receives: Drug: Oral dabrafenib and trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 month to 5 years (sliding timepoints)
Secondary outcomes (10)
Response ratio
Response ratio according to RECIST
Measured: 1 year after initiation of study treatment
Response duration
Duration of response for patients treated without subsequent surgery
Measured: From time of study drug discontinuation to time of observed increased tumor volume assessed up to 1 year
Operability after neoadjuvant trial treatment
Number of patients which become operable after neoadjuvant treatment
Measured: 1 year after initiation of study treatment
Progression-free survival 1 year
Defined as unchanged or diminished tumor volume
Measured: 1 year
Progression-free survival 2 years
Defined as unchanged or diminished tumor volume
Measured: 2 years
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
Measured: 1 year
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
Measured: 1 year
Cognitive status after treatment
Cognitive status assessed by CNS (central nervous system) Vital Signs 1 year after initiation of treatment and compared to baseline
Measured: 1 year
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
Measured: 1 year
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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2022
- Study start1 Sep 2023
- Primary completion10 Sep 2027 (estimated)
- Study completion10 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CraniopharyngiomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase 1, single arm, open label, multicenter.
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eva Marie Erfurth, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor-investigator, Eva Marie Erfurth, MD, PhD, Skane University Hospital
- Investigators
- Peter Siesjö, MD. PhD., Study chair, Department of Neurosurgery, SUS, Lund SwedenSara Kinhult, MD. PhD, Study chair, Department of Oncology, SUS, Lund SwedenEva Marie Erfurth, MD. PhD, Principal investigator, Department of Endocrinology, SUS, Lund, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05525273
- Sponsor's protocol ID
- ver 1-21
- Acronym
- Swecranio
- Status last verified
- Feb 2024
- First submitted
- 20 Apr 2022
- Last updated
- 14 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant and Postoperative Treatment With Dabrafenib and Trametinib in BRAF Mutated Papillary Craniopharyngioma
- ClinicalTrials.gov ID
- NCT05525273
- Acronym / sponsor ID
- Swecranio / ver 1-21
- Conditions
- Craniopharyngioma
- Keywords
- BRAF mutation, Dabrafenib, Trametinib, Neoadjuvant, Postoperative
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Eva Marie Erfurth, MD, PhDUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 10 Sep 2027 (estimated)
- Study completion
- 10 Apr 2028 (estimated)
- First posted
- 1 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 1, single arm, open label, multicenter.
| Arm | Type | Receives |
|---|---|---|
| Dabrafenib and trametinib | Experimental | Drug: Oral dabrafenib and trametinibDabrafenib 75 mg twice daily and trametinib 2 mg once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral dabrafenib and trametinibNeoadjuvant or postoperative treatment of patients with verified BRAF mutated papillary craniopharyngioma | Drug | Dabrafenib and trametinib |
Primary outcome
Tumor response
Time frame: 1 month to 5 years (sliding timepoints)
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
10 secondary outcomes
Response ratio
Time frame: 1 year after initiation of study treatment
Response duration
Time frame: From time of study drug discontinuation to time of observed increased tumor volume assessed up to 1 year
Operability after neoadjuvant trial treatment
Time frame: 1 year after initiation of study treatment
Progression-free survival 1 year
Time frame: 1 year
Progression-free survival 2 years
Time frame: 2 years
QOL after treatment
Time frame: 1 year
QOL after treatment
Time frame: 1 year
Cognitive status after treatment
Time frame: 1 year
Opthalmologic status after treatment
Time frame: 1 year
Hypothalamic status after treatment
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peter Siesjö, MD. PhD. study chair
Department of Neurosurgery, SUS, Lund Sweden
Sara Kinhult, MD. PhD study chair
Department of Oncology, SUS, Lund Sweden
Eva Marie Erfurth, MD. PhD principal investigator
Department of Endocrinology, SUS, Lund, Sweden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral dabrafenib and trametinib in people with Craniopharyngioma, run by Eva Marie Erfurth, MD, PhD at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Eva Marie Erfurth, MD. PhD. (+4646172363, eva_marie.erfurth@med.lu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor response (time frame: 1 month to 5 years (sliding timepoints)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2024.