Mucosal MelanomaPhase 2Neo PeLeMMNCT05545969
Neoadjuvant Pembrolizumab and Lenvatinib for Mucosal Melanoma
A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Mucosal Melanoma, run by Melanoma Institute Australia at 1 site in Australia.
Trial summary
In many cancers, early stage diagnosis and early treatment offers the best chance of a prolonged recurrence free- and overall survival. Neoadjuvant immunotherapy involves administering immune checkpoint inhibitors before surgical resection in high-risk resectable disease, such as mucosal melanoma. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Mucosal Melanoma
- What is being tested?
- Pembrolizumab and Lenvatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteAustralia
- Study dates
- Mar 2024to May 2036
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Histologically confirmed diagnosis of fully-resectable mucosal melanoma
- Pathological ± clinical confirmation that the presenting lesion(s) does not represent metastasis from an unknown primary cutaneous or ocular melanoma
- Measurable disease per RECIST
- Availability of a newly obtained core or excisional biopsy of an affected lesion which has not been previously irradiated
- Ability to swallow and retain oral medication
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- ECOG 0 - 1
- Adequate organ function per laboratory values
- Adequately controlled blood pressure with or without anti-hypertensive medications, defined as ≤ 150/90 mmHg at screening
- Anticpated life expectabcy of > 12 months.
Who cannot join
- A diagnosis of uveal or cutaneous melanoma
- A WOCBP who has a positive serum pregnancy test within 72 hours prior to starting study treatment
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease
- Prior systemic treatment for mucosal melanoma including investigational agents. Prior surgery is acceptable
- Major surgery within 3 weeks prior to first dose of lenvatinib
- Patients who have not recovered adequately from any toxicity from other permitted anti- cancer treatment regimens
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- Prior radiotherapy within 2 weeks of start of study treatment
- Received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study treatment
- Patient is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
- A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment
- Active autoimmune disease that has required systemic treatment in the past 12 months
- Known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has known central nervous system metastases and/or carcinomatous meningitis
- A history of (non-infectious) pneumonitis//interstitial lung disease that required steroids or has current pneumonitis or current interstitial lung disease
- Active infection requiring systemic therapy
- Known history of Human Immunodeficiency Virus, active Hepatitis B or C
- Has a known history of active TB
- A current diagnosis of any gastrointestinal condition that might affect the absorption of lenvatinib
- Has a pre-existing ≥ Grade 3 gastrointestinal adverse event or a non-gastrointestinal fistula
- Prolonged QT interval >480 ms
- History of, or current cardiovascular disease
- Has a history of, or a current bleeding or thrombotic disorders or patients at risk for severe haemorrhage
- Active haemoptysis
- Patients with a ≥2+ (≥100 mg/dL) proteinuria on urine dipstick testing
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
- Has had an allogenic tissue/solid organ transplant.
Trial locations and contacts
1 site in 1 country.
Australia1 site
Melanoma Institute Australia
Wollstonecraft, New South Wales, 2065
About this study
Official title: A Multicentre, Open Label, Phase II Study to Determine the Response to Neoadjuvant Pembrolizumab and Lenvatinib Followed by Adjuvant Treatment With Pembrolizumab and Lenvatinib in Mucosal Melanoma
In many cancers, early stage diagnosis and early treatment offers the best chance of a prolonged recurrence free- and overall survival. Neoadjuvant immunotherapy involves administering immune checkpoint inhibitors before surgical resection in high-risk resectable disease, such as mucosal melanoma. In resectable cancers, immune checkpoint inhibitors can enhance anti-tumour immunity by exploiting a competent immune system prior to surgery. Activating antigen-specific T cells found in the primary or baseline tumour continue to exert anti-tumour effects on remaining neoplastic cells after the resection of the original tumour, potentially preventing recurrences from occurring.
In resectable mucosal melanoma, an opportunity exists to improve clinical outcomes with the addition of neoadjuvant and adjuvant systemic therapy with nivolumab and lenvatinib as an adjunct to surgery.
- Conditions
- Mucosal Melanoma
- Being tested
- Pembrolizumab, Lenvatinib
- Keywords
- Immunotherapy, VEGF inhibitor, Neoadjuvant, Adjuvant, Pembrolizumab, Lenvatinib, Pathlogical respone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
LenvatinibDrug
Also called Lenvima
Lenvatinib is an oral potent multiple RTK inhibitor that selectively inhibits VEGF receptors, VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), fibroblast growth factor receptor (FGFR1-4), platelet derived growth factor (PDGFRα), stem cell factor receptor (KIT), and rearranged during transfection (RET)
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant and Adjuvant Therapy | Experimental | Neoadjuvant pembrolizumab \& lenvatinib for 6 weeks followed by definitive surgery then adjuvant pembrolizumab alone for 46 weeks Receives: Drug: Pembrolizumab; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in immune cell expression of HIF1 and immune cell densities
Tumour and immune cell expression of HIF1a and immune cell densities will be compared between baseline and day 8 melanoma tissue biopsies.
Measured: Baseline, week 1 week 6
Pathological response rate
Proportion of patients with complete absence of residual melanoma cells in the the planned resected tumour site(s) at week 6 surgery
Measured: 6 weeks
Secondary outcomes (1)
RECIST response rate
Proportion of patients with a complete or partial RECIST response; patients with no RECIST response and patients who have RECIST confirmed disease progression in the neoadjuvant period.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2022
- Study startMar 2024 (estimated)
- Primary completionMay 2026 (estimated)
- Study completionMay 2036 (estimated)
Why it stopped: Insufficient funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucosal 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Multicentre, open label, clinical trial
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Melanoma Institute Australia
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Georgina Long, MBBS, PhD, Principal investigator, Melanoma Institute Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05545969
- Sponsor's protocol ID
- MIA2022/442
- Acronym
- Neo PeLeMM
- Status last verified
- Jun 2024
- First submitted
- 6 Sep 2022
- Last updated
- 26 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Open Label, Phase II Study to Determine the Response to Neoadjuvant Pembrolizumab and Lenvatinib Followed by Adjuvant Treatment With Pembrolizumab and Lenvatinib in Mucosal Melanoma
- ClinicalTrials.gov ID
- NCT05545969
- Acronym / sponsor ID
- Neo PeLeMM / MIA2022/442
- Conditions
- Mucosal Melanoma
- Keywords
- Immunotherapy, VEGF inhibitor, Neoadjuvant, Adjuvant, Pembrolizumab, Lenvatinib, Pathlogical respone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Insufficient funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Melanoma Institute AustraliaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2024 (estimated)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2036 (estimated)
- First posted
- 19 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.
In many cancers, early stage diagnosis and early treatment offers the best chance of a prolonged recurrence free- and overall survival. Neoadjuvant immunotherapy involves administering immune checkpoint inhibitors before surgical resection in high-risk resectable disease, such as mucosal melanoma. In resectable cancers, immune checkpoint inhibitors can enhance anti-tumour immunity by exploiting a competent immune system prior to surgery. Activating antigen-specific T cells found in the primary or baseline tumour continue to exert anti-tumour effects on remaining neoplastic cells after the resection of the original tumour, potentially preventing recurrences from occurring.
In resectable mucosal melanoma, an opportunity exists to improve clinical outcomes with the addition of neoadjuvant and adjuvant systemic therapy with nivolumab and lenvatinib as an adjunct to surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Multicentre, open label, clinical trial
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant and Adjuvant Therapy | Experimental | Drug: Pembrolizumab, Drug: LenvatinibNeoadjuvant pembrolizumab \& lenvatinib for 6 weeks followed by definitive surgery then adjuvant pembrolizumab alone for 46 weeks |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent
- Histologically confirmed diagnosis of fully-resectable mucosal melanoma
- Pathological ± clinical confirmation that the presenting lesion(s) does not represent metastasis from an unknown primary cutaneous or ocular melanoma
- Measurable disease per RECIST
- Availability of a newly obtained core or excisional biopsy of an affected lesion which has not been previously irradiated
Key exclusion criteria (26 listed)
- A diagnosis of uveal or cutaneous melanoma
- A WOCBP who has a positive serum pregnancy test within 72 hours prior to starting study treatment
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease
- Prior systemic treatment for mucosal melanoma including investigational agents. Prior surgery is acceptable
- Major surgery within 3 weeks prior to first dose of lenvatinib
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 |
|---|---|---|
| PembrolizumabAlso: KeytrudaPembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. | Drug | Neoadjuvant and Adjuvant Therapy |
| LenvatinibAlso: LenvimaLenvatinib is an oral potent multiple RTK inhibitor that selectively inhibits VEGF receptors, VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), fibroblast growth factor receptor (FGFR1-4), platelet derived growth factor (PDGFRα), stem cell factor receptor (KIT), and rearranged during transfection (RET) | Drug | Neoadjuvant and Adjuvant Therapy |
Primary outcome
Change in immune cell expression of HIF1 and immune cell densities
Time frame: Baseline, week 1 week 6
Tumour and immune cell expression of HIF1a and immune cell densities will be compared between baseline and day 8 melanoma tissue biopsies.
Pathological response rate
Time frame: 6 weeks
Proportion of patients with complete absence of residual melanoma cells in the the planned resected tumour site(s) at week 6 surgery
1 secondary outcome
RECIST response rate
Time frame: 6 weeks
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 26 Jun 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. This study is not recruiting at the moment.
Georgina Long, MBBS, PhD principal investigator
Melanoma Institute Australia
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 Pembrolizumab and Lenvatinib in people with Mucosal Melanoma, run by Melanoma Institute Australia at 1 site in Australia.
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 26 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 26 Jun 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 Australia. 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 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?
Change in immune cell expression of HIF1 and immune cell densities (time frame: Baseline, week 1 week 6). 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 26 Jun 2024.