MelanomaPhase 1/2NCT02143050
Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients
A Phase 1/2 study testing Dabrafenib, Trametinib and Metformin in people with Melanoma, run by University of Louisville at 2 sites in United States.
Trial summary
The main purpose is to evaluate the clinical response, safety and survival of the FDA approved drugs Dabrafenib, Trametinib in combination with Metformin. Investigators hypothesize that the combination of an FDA approved non toxic dose of oral Metformin with the B-Raf inhibitor, Dabrafenib and the MEK inhibitor… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Dabrafenib, Trametinib and Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2014to 17 Nov 2017
- Phase
- Phase 1/2
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients > 18 years of age
- Patients with histologically confirmed BRAFV600E melanoma (Stage IIIC or
- Stage IV, American Joint Commission on Cancer)
- Eastern Cooperative Oncology Group Performance Status of 0 to 2
- Life expectancy > 3 months
- At least 1 site of radiographically measurable disease by RECIST 1.1
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- Adequate hematologic, renal, and liver function as defined by laboratory values performed within 42 days prior to initiation of dosing:
- Absolute neutrophil count > 1.0 x 10⁹/L
- Platelet count > 50 x 10⁹/L
- Hemoglobin > 8 g/dL
- Serum creatinine < 2 x upper limit of normal
- Total serum bilirubin < 3 x ULN
- Serum aspartate transaminase or serum alanine transaminase < 3 x ULN, and < 4 x ULN if liver metastases are present
- Fertile males should use an effective method of contraception during treatment and for at least 3 months after completion of treatment, as directed by their physician
- Pre-menopausal females and females < 2 years after the onset of menopause should have a negative pregnancy test at Screening. Pre-menopausal females must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of the study drug
- Females of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for > 1 year
- Before study entry, written informed consent must be obtained from the patient prior to performing any study related procedures
Who cannot join
- Prior treatment with Vemurafenib or Dabrafenib
- Known hypersensitivity to Metformin or any of its components
- Received radiotherapy for non CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation related toxicities to Grade < 1, except for alopecia
- Pregnant, breast feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures
- Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
James Graham Brown Cancer Center-Universityof Louisville
Louisville, Kentucky, 40202
James Graham Brown Cancer Center
Louisville, Kentucky, 40202
About this study
Official title: A Phase I/II Trial of Dabrafenib, Trametinib and Metformin Administered to Unresectable Stage IIIC and Stage IV BRAF V600E + Melanoma Patients
The main purpose is to evaluate the clinical response, safety and survival of the FDA approved drugs Dabrafenib, Trametinib in combination with Metformin. Investigators hypothesize that the combination of an FDA approved non toxic dose of oral Metformin with the B-Raf inhibitor, Dabrafenib and the MEK inhibitor, Trametinib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.
Read the detailed description
The study will be a single-arm, single center, uncontrolled phase I/II trial to estimate the safety of the combined treatments and then estimate the efficacy in terms of objective response rate in patients with stage IIIC and Stage IV melanoma treated with dabrafenib/trametinib and metformin.
- Conditions
- Melanoma
- Being tested
- Dabrafenib, Trametinib, Metformin
- Keywords
- Unresectable melanoma Stage IIIC and Stage IV BRAF V600E+
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DabrafenibDrug
Also called Tafinlar
TrametinibDrug
Also called Mekinist
MetforminDrug
Also called Glucophage
| Study group | Role | What they receive |
|---|---|---|
| Dabrafenib, Trametinib and Metformin | Experimental | Dabrafenib 150 mg PO BID until progression or unacceptable toxicity. Trametinib 2 mg PO QD until progression or unacceptable toxicity. Metformin 500 mg PO BID x 2 weeks, then 850 mg PO BID until progression or unacceptable toxicity. Receives: Drug: Dabrafenib; Drug: Trametinib; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Observation of two CTCAE drug related grade 4 toxicities in six patients.
During phase I, six patients will be enrolled and monitored for toxicities. If drug related deaths occur or more than two drug related CTCAE grade 4 toxicities occur the trial will be suspended. Phase II will estimate the efficacy of the drugs, enrolling 20 patients during stage 1 with an upper limit of 39 for the 2nd stage.
Measured: Duration of phase I portion, approxiately 6 months
Clinical Response Rate
Phase II will study the efficacy of the drugs enrolling 20 patients during stage I with an upper limit of 39 for the 2nd stage.
Measured: 6 years
Secondary outcomes (2)
To estimate the overall survival rates.
Patients will be contacted every 3 months following treatment administration for up to three years to obtain survival data.
Measured: Approximately 3 years
To explore the effect of other covariates on overall survival
To identify demographic, disease and treatment related effects on overall survival.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2014 (estimated)
- Study startSep 2014
- Primary completion17 Nov 2017
- Study completion17 Nov 2017
Why it stopped: No participant enrollment
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 University of LouisvilleThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Responsible party
- Principal investigator, Jason Chesney, University of Louisville
- Investigators
- Jason A Chesney, MD, PhD, Principal investigator, James Graham Brown Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02143050
- Sponsor's protocol ID
- BCC-MEL-14-01
- Status last verified
- Nov 2023
- First submitted
- 13 May 2014
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Dabrafenib, Trametinib and Metformin Administered to Unresectable Stage IIIC and Stage IV BRAF V600E + Melanoma Patients
- ClinicalTrials.gov ID
- NCT02143050
- Acronym / sponsor ID
- BCC-MEL-14-01
- Conditions
- Melanoma
- Keywords
- Unresectable melanoma Stage IIIC and Stage IV BRAF V600E+
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participant enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Study start
- Sep 2014
- Primary completion
- 17 Nov 2017 (actual)
- Study completion
- 17 Nov 2017 (actual)
- First posted
- 20 May 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 main purpose is to evaluate the clinical response, safety and survival of the FDA approved drugs Dabrafenib, Trametinib in combination with Metformin. Investigators hypothesize that the combination of an FDA approved non toxic dose of oral Metformin with the B-Raf inhibitor, Dabrafenib and the MEK inhibitor, Trametinib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.
Detailed description
The study will be a single-arm, single center, uncontrolled phase I/II trial to estimate the safety of the combined treatments and then estimate the efficacy in terms of objective response rate in patients with stage IIIC and Stage IV melanoma treated with dabrafenib/trametinib and metformin.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dabrafenib, Trametinib and Metformin | Experimental | Drug: Dabrafenib, Drug: Trametinib, Drug: MetforminDabrafenib 150 mg PO BID until progression or unacceptable toxicity. Trametinib 2 mg PO QD until progression or unacceptable toxicity. Metformin 500 mg PO BID x 2 weeks, then 850 mg PO BID until progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female patients > 18 years of age
- Patients with histologically confirmed BRAFV600E melanoma (Stage IIIC or
- Stage IV, American Joint Commission on Cancer)
- Eastern Cooperative Oncology Group Performance Status of 0 to 2
- Life expectancy > 3 months
Key exclusion criteria (5 listed)
- Prior treatment with Vemurafenib or Dabrafenib
- Known hypersensitivity to Metformin or any of its components
- Received radiotherapy for non CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation related toxicities to Grade < 1, except for alopecia
- Pregnant, breast feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures
- Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study
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 |
|---|---|---|
| DabrafenibAlso: Tafinlar | Drug | Dabrafenib, Trametinib and Metformin |
| TrametinibAlso: Mekinist | Drug | Dabrafenib, Trametinib and Metformin |
| MetforminAlso: Glucophage | Drug | Dabrafenib, Trametinib and Metformin |
Primary outcome
Observation of two CTCAE drug related grade 4 toxicities in six patients.
Time frame: Duration of phase I portion, approxiately 6 months
During phase I, six patients will be enrolled and monitored for toxicities. If drug related deaths occur or more than two drug related CTCAE grade 4 toxicities occur the trial will be suspended. Phase II will estimate the efficacy of the drugs, enrolling 20 patients during stage 1 with an upper limit of 39 for the 2nd stage.
Clinical Response Rate
Time frame: 6 years
Phase II will study the efficacy of the drugs enrolling 20 patients during stage I with an upper limit of 39 for the 2nd stage.
2 secondary outcomes
To estimate the overall survival rates.
Time frame: Approximately 3 years
To explore the effect of other covariates on overall survival
Time frame: 3 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
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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. This study is not recruiting at the moment.
Jason A Chesney, MD, PhD principal investigator
James Graham Brown Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dabrafenib, Trametinib and Metformin in people with Melanoma, run by University of Louisville at 2 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 17 inclusion and 5 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: withdrawn, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 combined 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.
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 withdrawn before enrolling participants, so there are no results.
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?
Observation of two CTCAE drug related grade 4 toxicities in six patients. (time frame: Duration of phase I portion, approxiately 6 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 18 Nov 2023.