MelanomaPhase 1NCT01611675
Leflunomide+Vemurafenib in V600 Mutant Met. Melanoma
A Phase 1 study testing Vemurafenib and Leflunomide in people with Melanoma, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
This research study was intended to be a Phase I/II clinical trial, but the trial was terminated before the phase 1 portion was completed. Phase I clinical trials test the safety of an investigational combination of drugs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Vemurafenib and Leflunomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2012to Jan 2014
- Phase
- Phase 1
- 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
- Histological or cytological confirmation of metastatic or unresectable melanoma
- Melanoma must be documented to contain a BRAF V600 mutation by a CLIA approved assay
- Measurable disease
- Less than or equal to 2 prior systemic treatment regimens for distant metastatic disease
Who cannot join
- Pregnant or breastfeeding
- Chemotherapy or radiation therapy within 4 weeks
- Prior therapy with a BRAF inhibitor or MEK inhibitor or leflunomide
- Receiving other study agents
- Known brain metastases that are symptomatic and require corticosteroids
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vemurafenib or leflunomide
Show all 9Show fewer
- Uncontrolled intercurrent illness
- HIV-positive
- History of a different malignancy
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: Leflunomide in Combination With Vemurafenib in Patients With V600 Mutant Metastatic Melanoma
This research study was intended to be a Phase I/II clinical trial, but the trial was terminated before the phase 1 portion was completed. Phase I clinical trials test the safety of an investigational combination of drugs. Phase I studies also try to define the appropriate dose of the investigational drug combination to use for the Phase II portion of the study, which will enroll more participants and continue to study the effects of the drug and the safest dose. "Investigational" means that the combination of vemurafenib and leflunomide is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved this drug combination for your type of cancer.
Genes are a specific part of your cell materials which send code messages to determine what the investigators bodies look like, such as eye color, and instruct cells to control growth and development of the body. Researchers have found that a large number of melanoma cells have mutations in the BRAF gene. Normally, the BRAF gene helps to control how cells grow. Mutations in the BRAF gene may disrupt this control and allow cells in the skin to change into cancer cells, in which case, the cells keep dividing and growing out of control. Specifically, it has been shown that vemurafenib blocks the effects of these mutations in the BRAF gene, and, as a result, may help to prevent cancer growth. The FDA has approved vemurafenib for use in patients with BRAF mutation positive melanoma that is unable to be removed by surgery (unresectable) or that has spread (metastatic).
Read more
Leflunomide is in a class of medications called disease-modifying antirheumatic drugs (DMARDs). It is FDA approved for the treatment of rheumatoid arthritis and it is believed to decrease inflammation in that setting. However it is not approved for treatment of melanoma. The researchers of this study believe this agent may help prevent cancer growth as well as enhance the properties of drugs that target the BRAF gene (such as vemurafenib) based on recently published laboratory research, and would like to learn more about any effects this combination may have on your disease.
The main purposes of this study are to determine the highest dose of vemurafenib and leflunomide that can be given in combination without causing severe side effects, to see whether the combination of vemurafenib and leflunomide is safe in participants with BRAF mutant metastatic melanoma and to learn if the combination of vemurafenib and leflunomide shows any signs of effectively treating your disease.
Read the detailed description
In this study we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have metastatic melanoma. For this reason, not everyone who participates in this research study will receive the same dose of the study drug. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses.
Both leflunomide and vemurafenib will be given as a pill to take by mouth. We will instruct you to take leflunomide pills once a day and vemurafenib pills twice a day. We will give you a study drug dosing calendar for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks).
At the start of the study you will take leflunomide alone for the first 14 days of cycle 1. For the first 3 days of cycle 1, you will receive a dose of leflunomide larger than you will be receiving for the rest of the research study (loading dose). These first few larger doses will introduce a certain amount of leflunomide into your body. The doses you receive after Day 3 will be lower but will be used to maintain that level of leflunomide in your body. Starting on Day 15, you will begin the twice-a-day Vemurafenib treatment while you continue to take leflunomide once daily.
During all cycles you will have routine blood tests, a physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking. These procedures will be performed once every cycle throughout the study.
If you have a skin lesion that can be surgically removed, the study doctor may ask you to undergo additional skin punch biopsies as part of this research study. These samples will be taken at three times throughout the study: before you begin the study treatment, after the initial 2-week study treatment of leflunomide alone, and then 2 weeks after starting the leflunomide and vemurafenib combination. We will assess your tumor by either CT scan or MRI scan once every eight weeks while you are in this research study.
After you have completed participation in this study we would like to keep track of your medical condition for the rest of your life. We would like to do this by calling you on the telephone once every 4 weeks to see how you are doing. Keeping in touch with you and checking your condition every year helps us to look at the long-term effects of the research study.
- Conditions
- Melanoma
- Being tested
- Vemurafenib, Leflunomide
- Keywords
- Metastatic, Unresectable, Clearly progressive, BRAF mutation
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VemurafenibDrug
take orally, twice daily
LeflunomideDrug
take orally, once daily
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Leflunomide + Vemurafenib Receives: Drug: Vemurafenib; Drug: Leflunomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Determine maximum tolerated dose of Vemurafenib + Leflunomide
To determine the maximum tolerated dose of vemurafenib plus leflunomide in patients with metastatic melanoma with V600 mutation with a requirement that fewer than one third of patients have dose-limiting toxicities. The goal of the study is to combine vemurafenib and leflunomide at their respective FDA approved doses and schedules.
Measured: 3 months
Phase II: Assess Efficacy of Leflunomide + Vemurafenib
To assess the efficacy (as measured by progression-free survival (PFS)) of patients with metastatic melanoma with V600 mutation treated with the combination of leflunomide and vemurafenib.
Measured: 2 years
Secondary outcomes (4)
Phase I: Assess Toxicities of Vemurafenib + Leflunomide
To assess toxicities of the combination of vemurafenib and leflunomide using CTCv4 toxicity criteria in patients with V600-expressing metastatic melanoma
Measured: 2 years
Phase II: Estimate Rates of Response using RECIST
To estimate rates of complete response and overall response
Measured: 2 years
Phase II: Impact of Leflunomide on Pharmacodynamic Endpoints
To investigate the impact of leflunomide on the pharmacodynamic endpoints defined in preclinical studies in serial tumor biopsy samples
Measured: 2 years
Phase II: Further Investigation of Safety of Vemurafenib + Leflunomide
To investigate further the safety of leflunomide in combination with vemurafenib using CTCv4 toxicity assessment criteria and determining the rate of all treatment-related toxicities
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2012 (estimated)
- Study startJul 2012
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: Adverse Events
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Keith Flaherty, Massachusetts General Hospital
- Investigators
- Keith Flaherty, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01611675
- Sponsor's protocol ID
- 12-088
- Status last verified
- Apr 2017
- First submitted
- 19 May 2012
- Last updated
- 6 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Leflunomide in Combination With Vemurafenib in Patients With V600 Mutant Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01611675
- Acronym / sponsor ID
- 12-088
- Conditions
- Melanoma
- Keywords
- Metastatic, Unresectable, Clearly progressive, BRAF mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Adverse Events
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 5 Jun 2012 (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.
This research study was intended to be a Phase I/II clinical trial, but the trial was terminated before the phase 1 portion was completed. Phase I clinical trials test the safety of an investigational combination of drugs. Phase I studies also try to define the appropriate dose of the investigational drug combination to use for the Phase II portion of the study, which will enroll more participants and continue to study the effects of the drug and the safest dose. "Investigational" means that the combination of vemurafenib and leflunomide is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved this drug combination for your type of cancer.
Genes are a specific part of your cell materials which send code messages to determine what the investigators bodies look like, such as eye color, and instruct cells to control growth and development of the body. Researchers have found that a large number of melanoma cells have mutations in the BRAF gene. Normally, the BRAF gene helps to control how cells grow. Mutations in the BRAF gene may disrupt this control and allow cells in the skin to change into cancer cells, in which case, the cells keep dividing and growing out of control. Specifically, it has been shown that vemurafenib blocks the effects of these mutations in the BRAF gene, and, as a result, may help to prevent cancer growth. The FDA has approved vemurafenib for use in patients with BRAF mutation positive melanoma that is unable to be removed by surgery (unresectable) or that has spread (metastatic).
Leflunomide is in a class of medications called disease-modifying antirheumatic drugs (DMARDs). It is FDA approved for the treatment of rheumatoid arthritis and it is believed to decrease inflammation in that setting. However it is not approved for treatment of melanoma. The researchers of this study believe this agent may help prevent cancer growth as well as enhance the properties of drugs that target the BRAF gene (such as vemurafenib) based on recently published laboratory research, and would like to learn more about any effects this combination may have on your disease.
The main purposes of this study are to determine the highest dose of vemurafenib and leflunomide that can be given in combination without causing severe side effects, to see whether the combination of vemurafenib and leflunomide is safe in participants with BRAF mutant metastatic melanoma and to learn if the combination of vemurafenib and leflunomide shows any signs of effectively treating your disease.
Detailed description
In this study we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have metastatic melanoma. For this reason, not everyone who participates in this research study will receive the same dose of the study drug. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses.
Both leflunomide and vemurafenib will be given as a pill to take by mouth. We will instruct you to take leflunomide pills once a day and vemurafenib pills twice a day. We will give you a study drug dosing calendar for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks).
At the start of the study you will take leflunomide alone for the first 14 days of cycle 1. For the first 3 days of cycle 1, you will receive a dose of leflunomide larger than you will be receiving for the rest of the research study (loading dose). These first few larger doses will introduce a certain amount of leflunomide into your body. The doses you receive after Day 3 will be lower but will be used to maintain that level of leflunomide in your body. Starting on Day 15, you will begin the twice-a-day Vemurafenib treatment while you continue to take leflunomide once daily.
During all cycles you will have routine blood tests, a physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking. These procedures will be performed once every cycle throughout the study.
If you have a skin lesion that can be surgically removed, the study doctor may ask you to undergo additional skin punch biopsies as part of this research study. These samples will be taken at three times throughout the study: before you begin the study treatment, after the initial 2-week study treatment of leflunomide alone, and then 2 weeks after starting the leflunomide and vemurafenib combination. We will assess your tumor by either CT scan or MRI scan once every eight weeks while you are in this research study.
After you have completed participation in this study we would like to keep track of your medical condition for the rest of your life. We would like to do this by calling you on the telephone once every 4 weeks to see how you are doing. Keeping in touch with you and checking your condition every year helps us to look at the long-term effects of the research study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Vemurafenib, Drug: LeflunomideLeflunomide + Vemurafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histological or cytological confirmation of metastatic or unresectable melanoma
- Melanoma must be documented to contain a BRAF V600 mutation by a CLIA approved assay
- Measurable disease
- Less than or equal to 2 prior systemic treatment regimens for distant metastatic disease
Key exclusion criteria (9 listed)
- Pregnant or breastfeeding
- Chemotherapy or radiation therapy within 4 weeks
- Prior therapy with a BRAF inhibitor or MEK inhibitor or leflunomide
- Receiving other study agents
- Known brain metastases that are symptomatic and require corticosteroids
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 |
|---|---|---|
| Vemurafenibtake orally, twice daily | Drug | Treatment Arm |
| Leflunomidetake orally, once daily | Drug | Treatment Arm |
Primary outcome
Phase I: Determine maximum tolerated dose of Vemurafenib + Leflunomide
Time frame: 3 months
To determine the maximum tolerated dose of vemurafenib plus leflunomide in patients with metastatic melanoma with V600 mutation with a requirement that fewer than one third of patients have dose-limiting toxicities. The goal of the study is to combine vemurafenib and leflunomide at their respective FDA approved doses and schedules.
Phase II: Assess Efficacy of Leflunomide + Vemurafenib
Time frame: 2 years
To assess the efficacy (as measured by progression-free survival (PFS)) of patients with metastatic melanoma with V600 mutation treated with the combination of leflunomide and vemurafenib.
4 secondary outcomes
Phase I: Assess Toxicities of Vemurafenib + Leflunomide
Time frame: 2 years
Phase II: Estimate Rates of Response using RECIST
Time frame: 2 years
Phase II: Impact of Leflunomide on Pharmacodynamic Endpoints
Time frame: 2 years
Phase II: Further Investigation of Safety of Vemurafenib + Leflunomide
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Adverse Events). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2017.
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
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.
Keith Flaherty, MD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vemurafenib and Leflunomide in people with Melanoma, run by Massachusetts General Hospital at 3 sites in United States.
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 4 inclusion and 9 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 6 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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: Adverse Events). 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?
Phase I: Determine maximum tolerated dose of Vemurafenib + Leflunomide (time frame: 3 months). 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 6 Apr 2017.