Malignant MelanomaPhase 1NCT00142454
NY-ESO-1 Protein Vaccine With Imiquimod in Melanoma (Adjuvant Setting)
A Phase 1 study testing Imiquimod and NY-ESO-1 protein in people with Malignant Melanoma, run by Ludwig Institute for Cancer Research at 1 site in United States.
Trial summary
This was a Phase 1, single-arm, open-label, pilot study of NY-ESO-1 protein vaccination with imiquimod as an adjuvant in patients with resected Stage IIB, IIC, and III malignant melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- Imiquimod and NY-ESO-1 protein
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2005to 25 Apr 2006
- Phase
- Phase 1
- 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
- Had histologically confirmed, resected American Joint Committee on Cancer Stage IIB, IIC or III malignant melanoma
- Fully recovered from surgery
- Age ≥ 18 years; children were excluded from this study, as the safety of imiquimod had not been established in patients below the age of 18
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Adequate organ and marrow function as defined below:
- absolute neutrophil count: ≥ 1500/μL
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- hemoglobin: ≥ 9 g/dL
- platelets: ≥ 100,000/μL
- total bilirubin: ≤ 1.5 × institutional upper limit of normal (ULN)
- aspartate aminotransferase/alanine aminotransferase (AST/ALT): ≤ 2.5 × institutional ULN
- creatinine: ≤ 1.5 × institutional ULN
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Received chemotherapy, immunotherapy (including interferon), or radiotherapy within 4 weeks prior to first dosing of study agent
- Prior treatment with NY-ESO-1 vaccines
- Known human immunodeficiency virus infection or autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions could have interfered with the evaluation of the induced immune response; patients with vitiligo or melanoma-associated hypopigmentation were not excluded
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to imiquimod or other agents used in the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would have limited compliance with study requirements
- Pregnancy or lactation
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- Women of childbearing potential not using a medically acceptable means of contraception
- Known history of inflammatory skin disorders, as imiquimod might have exacerbated these conditions
- Chronic corticosteroid or immunosuppressive therapies, as these might have interfered with the evaluation of the induced immune response
- Lack of availability for immunological and clinical follow-up assessments
Trial locations and contacts
1 site in 1 country.
About this study
Official title: NY-ESO-1 Protein Vaccination in Malignant Melanoma Administered With Imiquimod as Adjuvant
This was a Phase 1, single-arm, open-label, pilot study of NY-ESO-1 protein vaccination with imiquimod as an adjuvant in patients with resected Stage IIB, IIC, and III malignant melanoma. The primary study objective was to determine the safety of NY-ESO-1 protein/imiquimod treatment, and the secondary objective was to evaluate the immunogenicity of treatment.
Read the detailed description
Patients applied imiquimod (250 mg) topically to a designated area of healthy skin on the upper inner arm or inner thigh (the cream remained on the skin overnight for 6-10 hours) every day for 5 consecutive days (i.e., for the first 5 days of Cycles 1-3 and for the first 4 days of Cycle 4). The NY-ESO-1 protein (100 μg) was injected intradermally into the imiquimod-pretreated area on Day 3 of each cycle for 4 consecutive 21-day cycles.
Safety was monitored continuously. Immunization was assessed by the generation of NY-ESO-1-specific cluster of differentiation (CD)4+ and CD8+ T cell responses in enzyme-linked immunosorbent spot (ELISPOT) assays and by the development or augmentation of NY-ESO-1-specific antibody titers, assessed by enzyme-linked immunosorbent assay (ELISA).
Blood samples were obtained for the assessment of clinical biochemistry and hematology, and physical examinations were performed at baseline, on Day 1 of each cycle, and at a follow-up visit at Week 13.
Skin biopsies of the vaccinated area were obtained 48 hours after the last injection (Day 5 of Cycle 4). To avoid irritation, imiquimod was not applied after the biopsies.
- Conditions
- Malignant Melanoma
- Being tested
- Imiquimod, NY-ESO-1 protein
- Keywords
- Malignant melanoma, Stages IIB-III
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImiquimodDrug
Also called Aldara
Patients applied imiquimod cream at bedtime every day for 5 consecutive days (for the first 5 days of Cycles 1-3 and for the first 4 days of Cycle 4) at a dose of 250 mg as supplied in single-use packets to a 4 x 5 cm area of healthy skin, alternating among the extremities (upper inner arms and inner thighs) in each cycle. The cream was to be rubbed into the skin until it was no longer visible. Patients were encouraged to wash their hands before and after applying cream. The application site was not occluded. The next morning, 6 to 10 hours after initial application, the treated area was washed with mild soap and water to remove any residual cream.
NY-ESO-1 proteinBiological
NY-ESO-1 protein was injected intradermally by a study physician or nurse at a dose of 100 μg into the imiquimod-pretreated area on Day 3 of each cycle for 4 consecutive 21-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Imiquimod + NY-ESO-1 | Experimental | Patients applied topical imiquimod followed by vaccination with intradermal injections of the NY-ESO-1 protein. Receives: Drug: Imiquimod; Biological: NY-ESO-1 protein |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the time informed consent was signed through the last follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Measured: Up to 4 months
Secondary outcomes (2)
Number of Patients With Cellular Antibody Response to NY-ESO-1 at Two or More Post-vaccination Time Points
Assays to assess cluster of differentiation (CD)8+ and CD4+ antigen-specific responses were performed at baseline (Cycle 1 Day 1), throughout the vaccination period (Day 1 of Cycles 2 through 4 and Day 10 of each cycle), and at the 2 post-treatment follow-up visits (Weeks 13 and 16) by enzyme-linked immune absorbent spot (ELISPOT) assay following prior in vitro sensitization. A 3-fold increase in spot-forming cells over baseline defined a positive response. Suitable antigens may have included recombinant viral vectors encoding NY-ESO-1, or NY-ESO-1 overlapping peptides, depending upon availability.
Measured: Up to 4 months
Number of Patients With Humoral Antibody Response to NY-ESO-1
Assays to assess NY-ESO-1 specific antibodies were performed at baseline (Cycle 1 Day 1), throughout the vaccination period (Day 1 of Cycles 2 through 4 and Day 10 of each cycle), and at the 2 post-treatment follow-up visits (Weeks 13 and 16) by enzyme-linked immunosorbent assay (ELISA). Samples were diluted serially. The induction and augmentation of immunity were defined as an increase in antibody titer of ≥ 3× over buffer alone or ≥ 4× the pre-vaccination titer, respectively. Sera from the responding patients were tested a second time against a pool of NY-ESO-1 overlapping peptides to confirm NY-ESO-1 specificity; the number of patients in the table reflect the patients with confirmed NY-ESO-1 specificity.
Measured: Up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2005 (estimated)
- Study start24 Aug 2005
- Primary completion25 Apr 2006
- Study completion25 Apr 2006
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research Institute, New York City
- Responsible party
- Sponsor
- Investigators
- Nina Bhardwaj, MD, PhD, Principal investigator, NYU Langone HealthSylvia Adams, MD, Study director, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00142454
- Sponsor's protocol ID
- LUD2004-006
- Other IDs
- NYU 04-53
- Status last verified
- Oct 2022
- First submitted
- 1 Sep 2005
- Last updated
- 10 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Adams S, O'Neill DW, Nonaka D, Hardin E, Chiriboga L, Siu K, Cruz CM, Angiulli A, Angiulli F, Ritter E, Holman RM, Shapiro RL, Berman RS, Berner N, Shao Y, Manches O, Pan L, Venhaus RR, Hoffman EW, Jungbluth A, Gnjatic S, Old L, Pavlick AC, Bhardwaj N. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J Immunol. 2008 Jul 1;181(1):776-84. doi: 10.4049/jimmunol.181.1.776.
PubMed 18566444
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NY-ESO-1 Protein Vaccination in Malignant Melanoma Administered With Imiquimod as Adjuvant
- ClinicalTrials.gov ID
- NCT00142454
- Acronym / sponsor ID
- LUD2004-006
- Conditions
- Malignant Melanoma
- Keywords
- Malignant melanoma, Stages IIB-III
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- Cancer Research Institute, New York City
- Study start
- 24 Aug 2005 (actual)
- Primary completion
- 25 Apr 2006 (actual)
- Study completion
- 25 Apr 2006 (actual)
- First posted
- 2 Sep 2005 (estimated)
- Results
- Posted 22 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase 1, single-arm, open-label, pilot study of NY-ESO-1 protein vaccination with imiquimod as an adjuvant in patients with resected Stage IIB, IIC, and III malignant melanoma. The primary study objective was to determine the safety of NY-ESO-1 protein/imiquimod treatment, and the secondary objective was to evaluate the immunogenicity of treatment.
Detailed description
Patients applied imiquimod (250 mg) topically to a designated area of healthy skin on the upper inner arm or inner thigh (the cream remained on the skin overnight for 6-10 hours) every day for 5 consecutive days (i.e., for the first 5 days of Cycles 1-3 and for the first 4 days of Cycle 4). The NY-ESO-1 protein (100 μg) was injected intradermally into the imiquimod-pretreated area on Day 3 of each cycle for 4 consecutive 21-day cycles.
Safety was monitored continuously. Immunization was assessed by the generation of NY-ESO-1-specific cluster of differentiation (CD)4+ and CD8+ T cell responses in enzyme-linked immunosorbent spot (ELISPOT) assays and by the development or augmentation of NY-ESO-1-specific antibody titers, assessed by enzyme-linked immunosorbent assay (ELISA).
Blood samples were obtained for the assessment of clinical biochemistry and hematology, and physical examinations were performed at baseline, on Day 1 of each cycle, and at a follow-up visit at Week 13.
Skin biopsies of the vaccinated area were obtained 48 hours after the last injection (Day 5 of Cycle 4). To avoid irritation, imiquimod was not applied after the biopsies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imiquimod + NY-ESO-1 | Experimental | Drug: Imiquimod, Biological: NY-ESO-1 proteinPatients applied topical imiquimod followed by vaccination with intradermal injections of the NY-ESO-1 protein. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Had histologically confirmed, resected American Joint Committee on Cancer Stage IIB, IIC or III malignant melanoma
- Fully recovered from surgery
- Age ≥ 18 years; children were excluded from this study, as the safety of imiquimod had not been established in patients below the age of 18
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Adequate organ and marrow function as defined below:
Key exclusion criteria (10 listed)
- Received chemotherapy, immunotherapy (including interferon), or radiotherapy within 4 weeks prior to first dosing of study agent
- Prior treatment with NY-ESO-1 vaccines
- Known human immunodeficiency virus infection or autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions could have interfered with the evaluation of the induced immune response; patients with vitiligo or melanoma-associated hypopigmentation were not excluded
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to imiquimod or other agents used in the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would have limited compliance with study requirements
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 |
|---|---|---|
| ImiquimodAlso: AldaraPatients applied imiquimod cream at bedtime every day for 5 consecutive days (for the first 5 days of Cycles 1-3 and for the first 4 days of Cycle 4) at a dose of 250 mg as supplied in single-use packets to a 4 x 5 cm area of healthy skin, alternating among the extremities (upper inner arms and inner thighs) in each cycle. The cream was to be rubbed into the skin until it was no longer visible. Patients were encouraged to wash their hands before and after applying cream. The application site was not occluded. The next morning, 6 to 10 hours after initial application, the treated area was washed with mild soap and water to remove any residual cream. | Drug | Imiquimod + NY-ESO-1 |
| NY-ESO-1 proteinNY-ESO-1 protein was injected intradermally by a study physician or nurse at a dose of 100 μg into the imiquimod-pretreated area on Day 3 of each cycle for 4 consecutive 21-day cycles. | Biological | Imiquimod + NY-ESO-1 |
Primary outcome
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 4 months
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the time informed consent was signed through the last follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
2 secondary outcomes
Number of Patients With Cellular Antibody Response to NY-ESO-1 at Two or More Post-vaccination Time Points
Time frame: Up to 4 months
Number of Patients With Humoral Antibody Response to NY-ESO-1
Time frame: Up to 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 18566444Adams S, O'Neill DW, Nonaka D, Hardin E, Chiriboga L, Siu K, Cruz CM, Angiulli A, Angiulli F, Ritter E, Holman RM, Shapiro RL, Berman RS, Berner N, Shao Y, Manches O, Pan L, Venhaus RR, Hoffman EW, Jungbluth A, Gnjatic S, Old L, Pavlick AC, Bhardwaj N. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J Immunol. 2008 Jul 1;181(1):776-84. doi: 10.4049/jimmunol.181.1.776.
- Individual participant dataSharing planned: No
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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.
Nina Bhardwaj, MD, PhD principal investigator
NYU Langone Health
Sylvia Adams, MD study director
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imiquimod and NY-ESO-1 protein in people with Malignant Melanoma, run by Ludwig Institute for Cancer Research 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 12 inclusion and 10 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 10 Oct 2022. 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?
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?
Yes. Results are posted in the registry (first posted 22 Oct 2020). 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 Patients With Treatment-emergent Adverse Events (TEAEs) (time frame: Up to 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00142454, which also lists 1 linked publication.
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 10 Oct 2022.