Metastatic Melanoma (Carrying BRAF V600 Mutation)Phase 2NCT02052193
Evaluation of Photosensitivity in Dabrafenib or Vemurafenib Treated Metastatic Melanoma Patients - a Phase IIa/IIb Study
A Phase 2 study testing Dabrafenib and Vemurafenib in people with Metastatic Melanoma (Carrying BRAF V600 Mutation), run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
The BRAF inhibitors dabrafenib and vemurafenib belong both two a new class of potent anti-cancer drugs and are highly efficacious in tumors harboring the BRAF V600E mutation. Both drugs seem to be equally efficacious; however, their toxicity profile seems to differ. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma (Carrying BRAF V600 Mutation)
- What is being tested?
- Dabrafenib and Vemurafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2014to 15 Dec 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Signed informed consent must be obtained prior to performing any study-related procedures
- Male or female patients ≥ 18 years of age
- Patients with histologically confirmed metastatic melanoma (Stage III unresectable or Stage IV; American Joint Committee on Cancer, 7thEdition) with documented BRAF V600 mutation prior to first administration of dabrafenib or vemurafenib
- Patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 0.5 cm in the brain MRI with contrast
- ECOG performance status of 0 to 2
- Patients must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma
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- Adequate hematologic, renal, and liver function tests, as defined by the following laboratory values, performed within 7 days prior to first administration of dabrafenib or vemurafenib:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL
- Serum creatinine ≤ 1.5 times upper limit of normal (ULN) or creatine clearance (CrCl) > 50 mL/min by Cockcroft-Gault formula
- Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) ≤ 2.5 times ULN
- Serum bilirubin ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN if considered due to liver metastases)
- LVEF ≥ institutional LLN by ECHO
- Negative serum pregnancy test within 14 days prior to first administration of dabrafenib or vemurafenib in premenopausal women. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year
- Fertile women must use a highly effective method of contraception during treatment and for at least 1 month after completion of treatment, as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., < 1% per year) when used consistently and correctly Hormonal-based methods (e.g., oral contraceptives) are not permitted due to potential drug-drug interactions with dabrafenib. See also "Pregnancy Testing and Prevention", page39. At the discretion of the investigator, acceptable methods of contraception may include total abstinence, in cases where the lifestyle of the patient ensures compliance. Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception
- Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry
- Patients must be able to swallow tablets
Who cannot join
- Treatment with other UV sensitizing compounds such as psoralens, phenothiazine, tetracycline, amiodarone, phytopharmacons
- UV treatment within the last 3 months
- Previous treatment with a BRAF and/or MEK inhibitor.
- Cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of an investigational anti-cancer drug within 28 days preceding the first dose of dabrafenib or vemurafenib
- Current use of a prohibited medication or requires any of these medications during treatment with dabrafenib or vemurafenib
- Current use of therapeutic warfarin NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted
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- Unresolved toxicity of National Cancer Institute Common (NCI) Terminology Criteria for Adverse Events, v 4.0, ( Grade 2 or higher from previous anti-cancer therapy, except alopecia
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs
- A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection
- Known immediate or delayed hypersensitivity reaction to Vemurafenib or Dabrafenib or excipients
- Presence of non-cutaneous malignancies other than metastatic melanoma (Stage IV) within 5 years of study enrollment or any malignancy with confirmed activating RAS mutation
- Brain metastases that are symptomatic and/or requiring corticosteroids. Subjects on a stable dose of corticosteroids >1 month or who have been off of corticosteroids for at least 2 weeks can be enrolled. Subjects must also be off of enzyme-inducing anticonvulsants for >4 weeks
- Corrected QT (QTc) interval >450 msecs; history of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; abnormal cardiac valve morphology (≥ grade 2) documented by echocardiogram (subjects with minimal abnormalities [i.e., mild regurgitation/stenosis] can be entered on study with approval from the coordinating Investigator; or history of known cardiac arrhythmias
- Uncontrolled dysfunction of the electrolyte metabolism
- Known Long-QT-syndrome or intake of drugs which prolong the QT interval
- Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension, etc.), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol
- Patients with extensive tattoos that would restrict skin surface available for phototesting or obscure skin reactions
- Pregnant or lactating females
Trial locations and contacts
1 site in 1 country.
About this study
The BRAF inhibitors dabrafenib and vemurafenib belong both two a new class of potent anti-cancer drugs and are highly efficacious in tumors harboring the BRAF V600E mutation. Both drugs seem to be equally efficacious; however, their toxicity profile seems to differ. Serious phototoxicity has been observed in ~ 30% of patients treated with vemurafenib and in ~2 percent of patients treated with dabrafenib. These phototoxic reactions have developed in spite of informing the patients of this possible adverse event and instructing them to protect themselves. Manifestation of phototoxic reactions depends on the patient's habits of exposure and their efforts to protect themselves. The true frequency of photosensitivity can only be established by systematic photo-testing. In dermatology, standard test procedures with different UV-wavelengths and dosages have been established and the primary goal of this study will be to clarify the true rate of photosensitivity by these two BRAF-inhibitors. Furthermore, systematic experience will be collected how to best protect patients from phototoxic events. Dabrafenib and Vemurafenib are commercially available and considered standard of care for BRAF mutant metastatic melanoma in Germany. As the number of patients will not allow any conclusion with regard to efficacy or safety of vemurafenib, patients randomized to vemurafenib in part 2 will only remain on study until completion of phototesting.
- Being tested
- Dabrafenib, Vemurafenib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DabrafenibDrug
Measurement of toxicity related to UV exposure
VemurafenibDrug
Measurement of toxicity related to UV exposure
| Study group | Role | What they receive |
|---|---|---|
| Dabrafenib | Experimental | Dabrafenib 150mg BID orally Receives: Drug: Dabrafenib; Drug: Vemurafenib |
| Vemurafenib | Active comparator | Vemurafenib 960mg orally BID Receives: Drug: Dabrafenib; Drug: Vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of Solar Dermatitis due to Standardized UV Exposure in Patients treated with Dabrafenib
Measured: day 2-5
Degree of Solar Dermatitis due to Standardized UV Exposure in Patients treated with Dabrafenib or Vemurafenib
Measured: day 2-5
Secondary outcomes (2)
Number of Participants with Adverse Events treated with dabrafenib
Measured: day 1-28
Best overall response rates and progression free survival in patients treated with dabrafenib or vemurafenib using RECIST v1.1 criteria
Measured: Every 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionDec 2014
- Study completion15 Dec 2014
Why it stopped: Second cohort not opened because Simon-Two\_Step model failed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Melanoma (Carrying BRAF V600 Mutation)Studies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Claus Garbe, M.D., Principal investigator, Dept. of Dermatology, University Hopsital Tuebingen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02052193
- Sponsor's protocol ID
- ZDO 2012_PHOTOTOX
- Status last verified
- Jul 2015
- First submitted
- 28 Jan 2014
- Last updated
- 19 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Photosensitivity in Dabrafenib or Vemurafenib Treated Metastatic Melanoma Patients - a Phase IIa/IIb Study
- ClinicalTrials.gov ID
- NCT02052193
- Acronym / sponsor ID
- ZDO 2012_PHOTOTOX
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Second cohort not opened because Simon-Two\_Step model failed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Dec 2014 (actual)
- Study completion
- 15 Dec 2014 (actual)
- First posted
- 31 Jan 2014 (estimated)
- 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.
The BRAF inhibitors dabrafenib and vemurafenib belong both two a new class of potent anti-cancer drugs and are highly efficacious in tumors harboring the BRAF V600E mutation. Both drugs seem to be equally efficacious; however, their toxicity profile seems to differ. Serious phototoxicity has been observed in ~ 30% of patients treated with vemurafenib and in ~2 percent of patients treated with dabrafenib. These phototoxic reactions have developed in spite of informing the patients of this possible adverse event and instructing them to protect themselves. Manifestation of phototoxic reactions depends on the patient's habits of exposure and their efforts to protect themselves. The true frequency of photosensitivity can only be established by systematic photo-testing. In dermatology, standard test procedures with different UV-wavelengths and dosages have been established and the primary goal of this study will be to clarify the true rate of photosensitivity by these two BRAF-inhibitors. Furthermore, systematic experience will be collected how to best protect patients from phototoxic events. Dabrafenib and Vemurafenib are commercially available and considered standard of care for BRAF mutant metastatic melanoma in Germany. As the number of patients will not allow any conclusion with regard to efficacy or safety of vemurafenib, patients randomized to vemurafenib in part 2 will only remain on study until completion of phototesting.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dabrafenib | Experimental | Drug: Dabrafenib, Drug: VemurafenibDabrafenib 150mg BID orally |
| Vemurafenib | Active comparator | Drug: Dabrafenib, Drug: VemurafenibVemurafenib 960mg orally BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed informed consent must be obtained prior to performing any study-related procedures
- Male or female patients ≥ 18 years of age
- Patients with histologically confirmed metastatic melanoma (Stage III unresectable or Stage IV; American Joint Committee on Cancer, 7thEdition) with documented BRAF V600 mutation prior to first administration of dabrafenib or vemurafenib
- Patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 0.5 cm in the brain MRI with contrast
- ECOG performance status of 0 to 2
Key exclusion criteria (18 listed)
- Treatment with other UV sensitizing compounds such as psoralens, phenothiazine, tetracycline, amiodarone, phytopharmacons
- UV treatment within the last 3 months
- Previous treatment with a BRAF and/or MEK inhibitor.
- Cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of an investigational anti-cancer drug within 28 days preceding the first dose of dabrafenib or vemurafenib
- Current use of a prohibited medication or requires any of these medications during treatment with dabrafenib or vemurafenib
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 |
|---|---|---|
| DabrafenibMeasurement of toxicity related to UV exposure | Drug | Dabrafenib, Vemurafenib |
| VemurafenibMeasurement of toxicity related to UV exposure | Drug | Dabrafenib, Vemurafenib |
Primary outcome
Degree of Solar Dermatitis due to Standardized UV Exposure in Patients treated with Dabrafenib
Time frame: day 2-5
Degree of Solar Dermatitis due to Standardized UV Exposure in Patients treated with Dabrafenib or Vemurafenib
Time frame: day 2-5
2 secondary outcomes
Number of Participants with Adverse Events treated with dabrafenib
Time frame: day 1-28
Best overall response rates and progression free survival in patients treated with dabrafenib or vemurafenib using RECIST v1.1 criteria
Time frame: Every 3 months
Results and safety
The study was stopped early (reason given: Second cohort not opened because Simon-Two\_Step model failed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
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. This study is not recruiting at the moment.
Claus Garbe, M.D. principal investigator
Dept. of Dermatology, University Hopsital Tuebingen, Germany
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 Dabrafenib and Vemurafenib in people with Metastatic Melanoma (Carrying BRAF V600 Mutation), run by University Hospital Tuebingen at 1 site in Germany.
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 19 inclusion and 18 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: stopped early, as of the sponsor's last update on 19 Dec 2022. 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 Germany. 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?
The study was stopped early (reason given: Second cohort not opened because Simon-Two\_Step model failed). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Degree of Solar Dermatitis due to Standardized UV Exposure in Patients treated with Dabrafenib (time frame: day 2-5). The study lists 2 primary outcomes in all. 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 19 Dec 2022.