MelanomaPhase 1/2NCT02225366
Intratumoral Injections of LL37 for Melanoma
A Phase 1/2 study testing LL37 and Photographs in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the appropriate dose of LL37 that can be given to patients with melanoma. Researchers also want to learn if LL37 can stimulate the immune system to help control the disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- LL37 and Photographs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jul 2015to 24 Nov 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with histologically documented metastatic melanoma with at least 3 cutaneous lesions measuring over 5mm diameter. At least two lesions must be at least 10mm in diameter to serve as the injected disease. At least one other lesion measuring at least 5mm in diameter may serve as the non-injected lesion that will be measurable disease. Patients will have stage IIIB or IIIC (in-transit lesions with or without nodal metastases) or stage IV M1A disease with cutaneous or nodal lesions assessable for administration of LL37. Patients are only eligible if their melanoma deposits are not amenable to complete surgical excision. Skin lesions that are 5mm or greater are deemed measurable however lesions that are at least 10mm in diameter will be preferentially utilized for LL37 injection.
- Age greater than or equal to 18 years
- Clinical performance status of ECOG 0-2 within 30 days of signing informed consent.
- Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- Platelet count greater than or equal to 100,000/mm^3
- WBC >/=3000/mm^3
Show all 11Show fewer
- Serum ALT and AST less than three times the upper limit of normal
- Serum creatinine </= 2.0 mg/dl
- Seronegative for HIV antibody
- Patients with a negative pregnancy test (urine or serum) must be documented within 28 days of starting treatment for women of childbearing potential (WOCBP).
- Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, IUD, or sponge plus spermicide. Abstinence is an acceptable form of birth control.
Who cannot join
- Active autoimmune disease requiring disease modifying therapy.
- Concurrent systemic steroid therapy
- Any form of active primary or secondary immunodeficiency
- Prior malignancy except the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
- History of immunization with LL37
- Active systemic infections requiring intravenous antibiotics
- Prior systemic therapy, radiation therapy, or surgery within 28 days of starting study treatment
- Patients who are pregnant or nursing
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Induction of Antitumor Response in Melanoma Patients Using the Antimicrobial Peptide LL37
The goal of this clinical research study is to find the appropriate dose of LL37 that can be given to patients with melanoma. Researchers also want to learn if LL37 can stimulate the immune system to help control the disease.
Read the detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of LL37 based on when you join this study. Up to 4 dose levels of LL37 will be tested. Up to 2 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of LL37 is found.
Study Drug Administration:
One (1) time a week for 8 weeks, LL37 will be injected into 2-4 tumors. The injections will be done in the clinic.
Study Visits:
Within 1 week before your first study drug injection:
- You will have a physical exam.
- You will have a punch biopsy of a tumor. To collect a punch biopsy, the area of skin is numbed with anesthetic and a small cut is made to remove all or part of the affected tissue.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- The tumors will be measured and photographed. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are tumors on your face.
On Day 1:
- You will have a physical exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
On Day 2, you will have a punch biopsy of one of the injected tumors.
At Weeks 1, 2, 3, 4, 5, 6, 7, and 8:
- You will have a physical exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- At Weeks 1, 3, and 5 and 7, blood (about 4 tablespoons) will be drawn to study your immune response to LL37.
At Week 4, you will have a punch biopsy of one of the injected tumors and one of the tumors that you did not have an injection in. Photos of the tumors will be taken to show if the disease has responded to the study drug.
At Week 8:
- Photos of the LL37 injected sites will be taken to show if the disease has responded to the study drug.
- You will have CT scans to check the status of the disease.
Length of Treatment:
You will receive up to 8 weeks of study treatment. You will be taken off study if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up visits.
Off-Study Visit:
If you have to stop the study treatment earlier than planned because the disease got worse or you had intolerable side effects:
- You will have a physical exam.
- The tumors will be photographed and measured.
- Blood (about 4 teaspoons) will be drawn for routine tests and to study your immune response to LL37.
- You will have CT scans to check the status of the disease.
- You will have a punch biopsy of one of the injected tumors.
These off-study procedures will be completed within 14 days after your last dose of study treatment. You will be contacted by phone or clinic visit at 30 days (+/- 7 days) after your last dose to follow up on any drug-related toxicities which were present at the end of study.
Follow-Up:
Within 2 weeks after your last study drug dose and every 8-12 weeks after that, you will have scans to check the status of the disease. Your doctor will decide what type of scans you will have.
After your last study drug dose, at your routine clinic visits every 3 months for 1 year, the study staff will ask you about the status of disease, if possible. If you do not plan to continue to receive medical care at MD Anderson, the study staff will contact you by phone, email, or letter to ask about the status of disease. The calls should last about 5 minutes.
This is an investigational study. LL37 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.
Up to 36 participants will be treated in this study. All will take part at MD Anderson.
- Conditions
- Melanoma
- Being tested
- LL37, Photographs
- Keywords
- Melanoma, Metastatic, Antimicrobial peptide, LL37, Photographs
- 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.
LL37Biological
Starting dose 250 µg/tumor. The injections will be given every 7 days for up to 8 weeks.
PhotographsOther
Tumors measured and photographed one week before receiving LL37, and again at 4 weeks after LL37. Then photographs of the LL37 injected sites taken at 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Intra-Tumoral Injection of LL37 | Experimental | LL37 administered intratumorally in cutaneous or subcutaneous tumors at least 1 cm in diameter. Patients will receive weekly intratumoral injections of LL37 for up to 8 weeks. The injections will be given every 7 days (+/- 48 hours). Starting dose 250 µg/tumor. Receives: Biological: LL37; Other: Photographs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Optimal Biological Dose (OBD) of LL37 Based Upon Toxicity
Dose Limiting Toxicity defined as: a. Any grade 3 or 4 non-hematologic toxicity regardless of duration, except: Grade 3 skin reactions at injection sites - Grade 3 fever b. Grade 4 thrombocytopenia c. Grade 4 neutropenia lasting >2 weeks or associated with infection.
Measured: once a week, up to 8 weeks duration
Secondary outcomes (1)
Number of Participants With Antitumor Immune Response of Intra-Tumoral Injection of LL37
Response defined as experiencing either an immune-related complete or partial response (irCR or irPR), and the association between response and disease characteristics and T-cell responses will be assessed using logistic regression.
Measured: Radiologic evaluations in the form of CT scans of affected disease sites will be performed every 8 weeks (+/- 14 days) while on study, up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2014 (estimated)
- Study start8 Jul 2015
- Primary completion24 Nov 2020
- Study completion24 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Rodabe N. Amaria, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02225366
- Sponsor's protocol ID
- 2013-0422
- Other IDs
- 5P50CA093459-08, NCI-2014-02012
- Status last verified
- Dec 2021
- First submitted
- 22 Aug 2014
- Last updated
- 9 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction of Antitumor Response in Melanoma Patients Using the Antimicrobial Peptide LL37
- ClinicalTrials.gov ID
- NCT02225366
- Acronym / sponsor ID
- 2013-0422
- Conditions
- Melanoma
- Keywords
- Melanoma, Metastatic, Antimicrobial peptide, LL37, Photographs
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 8 Jul 2015 (actual)
- Primary completion
- 24 Nov 2020 (actual)
- Study completion
- 24 Nov 2020 (actual)
- First posted
- 26 Aug 2014 (estimated)
- Results
- Posted 9 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to find the appropriate dose of LL37 that can be given to patients with melanoma. Researchers also want to learn if LL37 can stimulate the immune system to help control the disease.
Detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of LL37 based on when you join this study. Up to 4 dose levels of LL37 will be tested. Up to 2 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of LL37 is found.
Study Drug Administration:
One (1) time a week for 8 weeks, LL37 will be injected into 2-4 tumors. The injections will be done in the clinic.
Study Visits:
Within 1 week before your first study drug injection:
- You will have a physical exam.
- You will have a punch biopsy of a tumor. To collect a punch biopsy, the area of skin is numbed with anesthetic and a small cut is made to remove all or part of the affected tissue.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- The tumors will be measured and photographed. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are tumors on your face.
On Day 1:
- You will have a physical exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
On Day 2, you will have a punch biopsy of one of the injected tumors.
At Weeks 1, 2, 3, 4, 5, 6, 7, and 8:
- You will have a physical exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- At Weeks 1, 3, and 5 and 7, blood (about 4 tablespoons) will be drawn to study your immune response to LL37.
At Week 4, you will have a punch biopsy of one of the injected tumors and one of the tumors that you did not have an injection in. Photos of the tumors will be taken to show if the disease has responded to the study drug.
At Week 8:
- Photos of the LL37 injected sites will be taken to show if the disease has responded to the study drug.
- You will have CT scans to check the status of the disease.
Length of Treatment:
You will receive up to 8 weeks of study treatment. You will be taken off study if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up visits.
Off-Study Visit:
If you have to stop the study treatment earlier than planned because the disease got worse or you had intolerable side effects:
- You will have a physical exam.
- The tumors will be photographed and measured.
- Blood (about 4 teaspoons) will be drawn for routine tests and to study your immune response to LL37.
- You will have CT scans to check the status of the disease.
- You will have a punch biopsy of one of the injected tumors.
These off-study procedures will be completed within 14 days after your last dose of study treatment. You will be contacted by phone or clinic visit at 30 days (+/- 7 days) after your last dose to follow up on any drug-related toxicities which were present at the end of study.
Follow-Up:
Within 2 weeks after your last study drug dose and every 8-12 weeks after that, you will have scans to check the status of the disease. Your doctor will decide what type of scans you will have.
After your last study drug dose, at your routine clinic visits every 3 months for 1 year, the study staff will ask you about the status of disease, if possible. If you do not plan to continue to receive medical care at MD Anderson, the study staff will contact you by phone, email, or letter to ask about the status of disease. The calls should last about 5 minutes.
This is an investigational study. LL37 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.
Up to 36 participants will be treated in this study. All will take part at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intra-Tumoral Injection of LL37 | Experimental | Biological: LL37, Other: PhotographsLL37 administered intratumorally in cutaneous or subcutaneous tumors at least 1 cm in diameter. Patients will receive weekly intratumoral injections of LL37 for up to 8 weeks. The injections will be given every 7 days (+/- 48 hours). Starting dose 250 µg/tumor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with histologically documented metastatic melanoma with at least 3 cutaneous lesions measuring over 5mm diameter. At least two lesions must be at least 10mm in diameter to serve as the injected disease. At least one other lesion measuring at least 5mm in diameter may serve as the non-injected lesion that will be measurable disease. Patients will have stage IIIB or IIIC (in-transit lesions with or without nodal metastases) or stage IV M1A disease with cutaneous or nodal lesions assessable for administration of LL37. Patients are only eligible if their melanoma deposits are not amenable to complete surgical excision. Skin lesions that are 5mm or greater are deemed measurable however lesions that are at least 10mm in diameter will be preferentially utilized for LL37 injection.
- Age greater than or equal to 18 years
- Clinical performance status of ECOG 0-2 within 30 days of signing informed consent.
- Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- Platelet count greater than or equal to 100,000/mm^3
Key exclusion criteria (8 listed)
- Active autoimmune disease requiring disease modifying therapy.
- Concurrent systemic steroid therapy
- Any form of active primary or secondary immunodeficiency
- Prior malignancy except the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
- History of immunization with LL37
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 |
|---|---|---|
| LL37Starting dose 250 µg/tumor. The injections will be given every 7 days for up to 8 weeks. | Biological | Intra-Tumoral Injection of LL37 |
| PhotographsTumors measured and photographed one week before receiving LL37, and again at 4 weeks after LL37. Then photographs of the LL37 injected sites taken at 8 weeks. | Other | Intra-Tumoral Injection of LL37 |
Primary outcome
Number of Participants With Optimal Biological Dose (OBD) of LL37 Based Upon Toxicity
Time frame: once a week, up to 8 weeks duration
Dose Limiting Toxicity defined as: a. Any grade 3 or 4 non-hematologic toxicity regardless of duration, except: Grade 3 skin reactions at injection sites - Grade 3 fever b. Grade 4 thrombocytopenia c. Grade 4 neutropenia lasting >2 weeks or associated with infection.
1 secondary outcome
Number of Participants With Antitumor Immune Response of Intra-Tumoral Injection of LL37
Time frame: Radiologic evaluations in the form of CT scans of affected disease sites will be performed every 8 weeks (+/- 14 days) while on study, up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Rodabe N. Amaria, MD principal investigator
M.D. Anderson Cancer Center
1 site 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 LL37 and Photographs in people with Melanoma, run by M.D. Anderson Cancer Center 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 11 inclusion and 8 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: finished, as of the sponsor's last update on 9 Dec 2021. 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 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?
Yes. Results are posted in the registry (first posted 9 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Optimal Biological Dose (OBD) of LL37 Based Upon Toxicity (time frame: once a week, up to 8 weeks duration). 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 9 Dec 2021.