MelanomaEarly Phase 1Mel61NCT02382549
A Clinical Trial to Evaluate a Melanoma Helper Peptide Vaccine Plus Dabrafenib and Trametinib
A Early Phase 1 study testing BRAF inhibitor, 6MHP and MEK inhibitor in people with Melanoma, run by Craig L Slingluff, Jr at 1 site in United States.
Trial summary
This study evaluates whether it is safe to administer a helper peptide vaccine with BRAF inhibitor and MEK inhibitor therapy. This study will also evaluate the effects of the combination of the peptide vaccine and BRAF inhibitors/MEK inhibitors on the immune system. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- BRAF inhibitor, 6MHP and MEK inhibitor
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to 28 Feb 2022
- Phase
- Early 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
- Cohort 1 (Advanced): Measurable stage IIIB, IIIC, IIID or IV melanoma with clinical or radiological evidence of disease. These participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Staging must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on the revised AJCC 8th Edition staging system (Appendix 2) 66.
- Cohort 2 (Neo-adjuvant): Resectable stage IIIB, IIIC, IIID, or IV melanoma at initial presentation or subsequent recurrence. These participants have disease amenable to complete surgical resection at the time of enrollment in the study. The resectable disease does not need to be measurable by RECIST v1.1 criteria.
- Cohort 3 (Adjuvant): Participants with stage IIIA, IIIB, IIIC, IIID or IV melanoma resected to no evidence of disease. Participants must initiate therapy within 12 weeks of last surgical resection and within 12 weeks of being rendered clinically free of disease by non-surgical approaches Patients that have undergone ablative therapy to a metastatic lesion (e.g. GKRS, radiofrequency ablation) that manifest no additional sites of disease at enrollment are eligible for treatment on cohort 3
- Participants must be eligible to be treated with BRAF inhibitor and MEK inhibitor combination.
- Participants with prior therapy with targeted therapies specific for mutated BRAF including BRAF and/or MEK inhibitors are eligible provided that there was clinical benefit to prior therapy with these agents as judged by the treating physician. There must be an interval of at least 6 months from the last BRAF/MEK therapy and enrollment in this clinical study
- Participants will be required to have radiological studies at baseline to establish measurable disease for cohort 1 or to prove lack of distant metastases for cohorts 2 and 3. Required studies include:
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- Chest CT scan,
- Abdominal and pelvic CT scan, and
- Head CT scan or MRI
- Participants in cohorst 1 \& 2 who have metastatic melanoma safely available for biopsy pretreatment and on day 22 must consent to having those biopsies. These metastases may be in nodes, skin, soft tissue, liver, or other sites that can be accessed by needle biopsy, incisional or excisional biopsy, with or without image guidance.
- 3.1.6 Participants who have had brain metastases will be eligible if all of the following are true:
- Each brain metastasis must have been completely removed by surgery or each unresected brain metastasis must have been treated with stereotactic radiosurgery or systemic immunotherapy
- There has been no evident growth of any brain metastasis since the most recent treatment if the last treatment is >4 weeks prior to enrollment
- No brain metastasis is > 2 cm in diameter at the time of registration
- Neurologic symptoms have returned to baseline off steroids,
- Subjects are not using steroids for at least 7 days prior to registration.
- The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed ≥ 1 week prior to registration
- ECOG performance status of 0-2
- Participants must have the ability and willingness to give informed consent
- Laboratory parameters as follows:
- ANC > 1000/mm3
- Platelets > 100,000/mm3
- Hgb > 9 g/dL
- HgB-A1c ≤ 8.5%
- AST and ALT up to 2.5 x upper limits of normal (ULN). Patients known to have Gilbert's disease may be eligible with AST and ALT up to 5 x ULN.
- Bilirubin up to 2.5 x ULN
- Alkaline phosphatase up to 2.5 x ULN.
- Creatinine up to 1.5 x ULN
- Age 18 years or older at registration
- Participants must have at least two intact (undissected) axillary and/or inguinal lymph node basins
Who cannot join
- Participants who have received the following medications or treatments at any time within 4 weeks of registration:
- • Chemotherapy
- Interferon (e.g. Intron-A®)
- Radiation therapy (Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week and ≤ 6 months prior to registration)
- Allergy desensitization injections
- Corticosteroids, administered transdermally, parenterally or orally. Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are not permitted. Topical corticosteroids are acceptable.
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- Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
- Interleukins (e.g. Proleukin®)
- Any investigational medication
- HIV positivity or evidence of active Hepatitis C virus.
- Participants who are currently receiving nitrosoureas or who have received this therapy 6 weeks prior to registration
- Participants who are currently receiving a checkpoint molecule blockade therapy, or who have received this therapy within 3weeks prior to registration.
- Participants with known or suspected allergies to any component of the vaccine.
- Participants may not have been vaccinated previously with any of the synthetic peptides included in this protocol. Participants who have received vaccinations containing agents other than the synthetic peptides included in this protocol and have recurred during or after administration of the vaccine will be eligible to enroll 12 weeks following their last vaccination.
- Pregnancy.
- Female participants must not be breastfeeding
- Participants in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator.
- Participants classified according to the New York Heart Association classification as having Class III or IV heart disease.
- Participants with uncontrolled diabetes, defined as having a HgB-A1c greater than 7.5%.
- Participants must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. Participants with an active autoimmune disorder requiring these therapies are also excluded.
- Participants who have another cancer diagnosis, except that the following diagnoses will be allowed:
- squamous cell cancer of the skin without known metastasis
- basal cell cancer of the skin without known metastasis
- carcinoma in situ of the breast (DCIS or LCIS)
- carcinoma in situ of the cervix
- any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis for over 3 years
- Participants with known addiction to alcohol or drugs who are actively taking those agents, or participants with recent (within 1 year of registration) or ongoing illicit IV drug use.
- Body weight < 110 pounds
- Participants with a known history of glucose-6-phosphate dehydrogenase deficiency.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22908
About this study
Official title: A TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A HELPER PEPTIDE VACCINE PLUS COMBINATION OF BRAF INHIBITION AND MEK INHIBITION (MEL61)
This study evaluates whether it is safe to administer a helper peptide vaccine with BRAF inhibitor and MEK inhibitor therapy. This study will also evaluate the effects of the combination of the peptide vaccine and BRAF inhibitors/MEK inhibitors on the immune system. We will monitor these effects by performing tests in the laboratory on participants' blood and tumor samples.
- Conditions
- Melanoma
- Being tested
- BRAF inhibitor, 6MHP, MEK inhibitor
- Keywords
- vaccine, peptide, dabrafenib, trametinib, Montanide ISA-51, MEKINIST, Tafinlar, BRAF inhibitor, MEK inhibitor, BRAFi, MEKi, encorafenib, binimetinib, BRAFTOVI, MEKTOVI, vemurafenib, Zeldoraf, cobimetinib, Cotellic, 6MHP
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BRAF inhibitorDrug
BRAF inhibitor
6MHPBiological
Also called 6 melanoma helper peptide vaccine
6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
MEK inhibitorDrug
MEK Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| 6MHP and MEKi and BRAFi | Experimental | The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 36, 57, 78. All peptide vaccines are administered intradermally and subcutaneously.
A selective BRAF inhibitor and a selective MEK inhibitor will be administered in accordance with the prescribing information. Receives: Drug: BRAF inhibitor; Biological: 6MHP; Drug: MEK inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event profile for the combination of BRAFi, MEKi, and 6MHP
Measured: 30 days after the last vaccination with 6MHP
CD4+ T cell responses in the blood
CD4+ T cell responses to the peptide vaccine
Measured: through day 85
Secondary outcomes (2)
An evaluation of the infiltration of T cells into melanoma metastases pre and post-vaccination.
Measured: pre-vaccine and day 22
Antibody responses against 6MHP
An evaluation of the development of antibdoy responses following vaccination
Measured: through day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2015 (estimated)
- Study startApr 2016
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Why it stopped: The study was terminated because of slow accruals.
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.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Craig L Slingluff, Jr
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Craig L Slingluff, Jr, University of Virginia
- Investigators
- Elizabeth Gaughan, MD, Principal investigator, University of VirginiaCraig L. Slingluff, Jr., MD, Study director, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02382549
- Sponsor's protocol ID
- 17700
- Other IDs
- R01CA178846
- Acronym
- Mel61
- Status last verified
- Dec 2023
- First submitted
- 2 Mar 2015
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A HELPER PEPTIDE VACCINE PLUS COMBINATION OF BRAF INHIBITION AND MEK INHIBITION (MEL61)
- ClinicalTrials.gov ID
- NCT02382549
- Acronym / sponsor ID
- Mel61 / 17700
- Conditions
- Melanoma
- Keywords
- vaccine, peptide, dabrafenib, trametinib, Montanide ISA-51, MEKINIST, Tafinlar, BRAF inhibitor
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated because of slow accruals.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Craig L Slingluff, JrUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2016
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 6 Mar 2015 (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 study evaluates whether it is safe to administer a helper peptide vaccine with BRAF inhibitor and MEK inhibitor therapy. This study will also evaluate the effects of the combination of the peptide vaccine and BRAF inhibitors/MEK inhibitors on the immune system. We will monitor these effects by performing tests in the laboratory on participants' blood and tumor samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 6MHP and MEKi and BRAFi | Experimental | Drug: BRAF inhibitor, Biological: 6MHP, Drug: MEK inhibitorThe vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 36, 57, 78. All peptide vaccines are administered intradermally and subcutaneously. A selective BRAF inhibitor and a selective MEK inhibitor will be administered in accordance with the prescribing information. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Cohort 1 (Advanced): Measurable stage IIIB, IIIC, IIID or IV melanoma with clinical or radiological evidence of disease. These participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Staging must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on the revised AJCC 8th Edition staging system (Appendix 2) 66.
- Cohort 2 (Neo-adjuvant): Resectable stage IIIB, IIIC, IIID, or IV melanoma at initial presentation or subsequent recurrence. These participants have disease amenable to complete surgical resection at the time of enrollment in the study. The resectable disease does not need to be measurable by RECIST v1.1 criteria.
- Cohort 3 (Adjuvant): Participants with stage IIIA, IIIB, IIIC, IIID or IV melanoma resected to no evidence of disease. Participants must initiate therapy within 12 weeks of last surgical resection and within 12 weeks of being rendered clinically free of disease by non-surgical approaches Patients that have undergone ablative therapy to a metastatic lesion (e.g. GKRS, radiofrequency ablation) that manifest no additional sites of disease at enrollment are eligible for treatment on cohort 3
- Participants must be eligible to be treated with BRAF inhibitor and MEK inhibitor combination.
- Participants with prior therapy with targeted therapies specific for mutated BRAF including BRAF and/or MEK inhibitors are eligible provided that there was clinical benefit to prior therapy with these agents as judged by the treating physician. There must be an interval of at least 6 months from the last BRAF/MEK therapy and enrollment in this clinical study
Key exclusion criteria (29 listed)
- Participants who have received the following medications or treatments at any time within 4 weeks of registration:
- HIV positivity or evidence of active Hepatitis C virus.
- Participants who are currently receiving nitrosoureas or who have received this therapy 6 weeks prior to registration
- Participants who are currently receiving a checkpoint molecule blockade therapy, or who have received this therapy within 3weeks prior to registration.
- Participants with known or suspected allergies to any component of the vaccine.
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 |
|---|---|---|
| BRAF inhibitorBRAF inhibitor | Drug | 6MHP and MEKi and BRAFi |
| 6MHPAlso: 6 melanoma helper peptide vaccine6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides | Biological | 6MHP and MEKi and BRAFi |
| MEK inhibitorMEK Inhibitor | Drug | 6MHP and MEKi and BRAFi |
Primary outcome
Adverse event profile for the combination of BRAFi, MEKi, and 6MHP
Time frame: 30 days after the last vaccination with 6MHP
CD4+ T cell responses in the blood
Time frame: through day 85
CD4+ T cell responses to the peptide vaccine
2 secondary outcomes
An evaluation of the infiltration of T cells into melanoma metastases pre and post-vaccination.
Time frame: pre-vaccine and day 22
Antibody responses against 6MHP
Time frame: through day 85
Results and safety
The study was stopped early (reason given: The study was terminated because of slow accruals.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 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.
Elizabeth Gaughan, MD principal investigator
University of Virginia
Craig L. Slingluff, Jr., MD study director
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing BRAF inhibitor, 6MHP and MEK inhibitor in people with Melanoma, run by Craig L Slingluff, Jr at 1 site 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 30 inclusion and 29 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 12 Dec 2023. 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 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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: The study was terminated because of slow accruals.). 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?
Adverse event profile for the combination of BRAFi, MEKi, and 6MHP (time frame: 30 days after the last vaccination with 6MHP). 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 12 Dec 2023.