MelanomaPhase 1/2NCT01079741
Safety Study of Adjuvant Vaccine to Treat Melanoma Patients
A Phase 1/2 study testing NY-ESO-1 protein; Poly-ICLC; Montanide in people with Melanoma, run by Nina Bhardwaj at 1 site in United States.
Trial summary
The incidence of melanoma is increasing with an estimated incidence of 59,940 cases and an annual death rate of 8110 in 2007. Although patients diagnosed with early stage disease have an excellent clinical outcome, patients diagnosed with advanced or recurrent disease, continue to have a high mortality rate, even with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- NY-ESO-1 protein; Poly-ICLC; Montanide
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to 11 Mar 2013
- 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
- Histological diagnosis of malignant melanoma, stages IIB-IV in radiologically confirmed cCr without clinical evidence of disease.
- At least 4 weeks since surgery prior to first dosing of study agent.
- Laboratory values within the following limits:
- Hemoglobin > 10.0 g/dL
- Neutrophil count > 1.5 x l09/L
- Lymphocyte count > Lower limit of institutional normal
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- Platelet count > 80 x l09/L
- Serum creatinine < 2.0 mg/dL
- Serum bilirubin < 2 x upper limit of institutional normal
- AST/ALT < 2 x upper limit of institutional normal
- Patients must have an ECOG performance status of <2 (ECOG criteria published in [67].
- Life expectancy > 6 months.
- Age > 18 years.
- Able and willing to give written informed consent for participation in the trial (see Section 12.2).
Who cannot join
- Serious illnesses, e.g., serious infections requiring antibiotics.
- Previous bone marrow or stem cell transplant.
- History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo.
- Metastatic disease to the central nervous system.
- Other malignancy within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ.
- Prior chemotherapy or vaccine therapy.
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- Radiation therapy, biological therapy or surgery within 4 weeks prior to first dose of study agent.
- Concomitant treatment with systemic corticosteroids greater than physiologic doses. Topical (but not at the proposed vaccination sites) or inhalational steroids are permitted.
- Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
- Pregnancy or lactation.
- Women of childbearing potential not using a medically acceptable means of contraception.
- Psychiatric or addictive disorders that may compromise the ability to give informed consent.
- Lack of availability of the patient for immunological and clinical follow-up assessment.
- Children <18 years of age who cannot undergo the leukapheresis procedure, do not meet the disease staging and/or the size criteria for frequent blood donations
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University Langone Medical Center
New York, New York, 10016
About this study
Official title: Phase I/Phase II Open Label Study of the TLR3 Agonist Poly-ICLC as an Adjuvant for NY-ESO-1 Protein Vaccination With or Without Montanide ® ISA-51 VG in Patients With High Risk Melanoma in Complete Clinical Remission
The incidence of melanoma is increasing with an estimated incidence of 59,940 cases and an annual death rate of 8110 in 2007. Although patients diagnosed with early stage disease have an excellent clinical outcome, patients diagnosed with advanced or recurrent disease, continue to have a high mortality rate, even with initial optimal surgical resection. Effective adjuvant strategies are needed to increase the time to progression and to decrease the recurrence rate. Immunotherapy has long been recognized as a potential therapy for melanoma; the goal of adjuvant vaccine therapy is to train the endogenous immune system to recognize and target minimal residual disease.
Read the detailed description
This is a Phase I open label dose escalation study of the TLR3 agonist Poly-ICLC as an adjuvant for NY-ESO-1 protein vaccination in patients with high risk melanoma in clinical complete remission (cCr), followed by a randomized Phase II component in which patients will be randomized to subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide® ISA-51 VG (Montanide) (Arm B).
Patients with histological confirmed malignant melanoma, AJCC Stages: IIB, IIC, III or IV, who are in complete clinical remission (cCr) but at high risk of disease recurrence, will be eligible for enrollment, regardless of whether antigen expression in the autologous tumor can be demonstrated by either PCR or immunohistochemistry.
Primary Objectives:
- Phase I: To define the safety of subcutaneous vaccination with NY-ESO-1 protein, Montanide and escalating doses of Poly-ICLC.
- Phase II: To evaluate the induction of humoral and T cell (CD4+ and CD8+) immunity to subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given with or without Montanide.
Exploratory analyses:
- Evaluation of primary tumor expression of NY-ESO-1 by IHC or RT-PCR.
- Histologic quantitation of original tumor TILs (tumor infiltrating lymphocytes), CD3+ cells, evaluation of mitotic index and correlation of this data with immunologic response.
- Correlation of NY-ESO-1 specific T cell responses with HLA type
- Investigation of polymorphisms for TLR3 through germline SNP analysis.
- Clinical Outcome (Time to Progression) reported descriptively.
- Skin section analysis of protein/adjuvant treated sites for immune cell infiltration and gene expression analysis
- Conditions
- Melanoma
- Being tested
- NY-ESO-1 protein; Poly-ICLC; Montanide
- Keywords
- Melanoma, Skin Cancer, Adjuvant Therapy, Oncogenesis, LAGE, Cancer Immunity, Neoplasms, Immunogenicity, Vaccine, Immunotherapy
- Medical subject headings
- Melanoma, Skin Neoplasms, Carcinogenesis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NY-ESO-1 protein; Poly-ICLC; MontanideBiological
Also called Cancer-Testis (CT) antigen expression: NY-ESO-1, Poly ICLC: carboxymethylcellulose, polyinosinic-polycytidylic acid & poly-L-lysine double-stranded RNA, Montanide® ISA-51 VG: mineral oil-based adjuvant; also called (IFA)incomplete Freund's adjuvant.
Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen (100µg) and Montanide (1.1mL) will be held constant.
Phase II: The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B).
| Study group | Role | What they receive |
|---|---|---|
| Dose-escalation component | Experimental | Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen and Montanide will be held constant. Receives: Biological: NY-ESO-1 protein; Poly-ICLC; Montanide |
| Phase II is the randomized component. | Active comparator | The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B). Receives: Biological: NY-ESO-1 protein; Poly-ICLC; Montanide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I, Number of Participants With SAE and DLT
Safety measured by number of Serious Adverse Events per the CTEP v4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) and Dose Limiting Toxicity (DLT).
Measured: 52 weeks
Secondary outcomes (2)
CD4+ and CD8+ Response
Cellular response evaluated for the induction of cellular T cell (CD4+ and CD8+) immunity to subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given with or without Montanide. Number of participants with increase CD4+ and CD8+ levels.
Measured: Up to 52 weeks
NY-ESO-1 Expression by IHC
Analysis of immune cell infiltration at the injection site by IHC. IHC analysis of immune cell infiltration was performed for each arm using a scoring system. 0: No expression of the marker of interest, 1: single cells or small clusters (<5 cells together) expressing marker of interest, 2: medium size clusters of cells expressing marker of interest, and 3: huge and homogeneously positive clusters of cells expressing marker of interest.
Measured: up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2010 (estimated)
- Study startSep 2010
- Primary completion11 Mar 2013
- Study completion11 Mar 2013
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.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nina Bhardwaj
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig Institute for Cancer Research, Oncovir, Inc., Cancer Research Institute, New York City
- Responsible party
- Sponsor-investigator, Nina Bhardwaj, Icahn School of Medicine at Mount Sinai
- Investigators
- Nina Bhardwaj, MD, PhD, Principal investigator, NYU Langone HealthAnna Pavlick, D.O., Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01079741
- Sponsor's protocol ID
- GCO 13-1391
- Status last verified
- Nov 2017
- First submitted
- 2 Mar 2010
- Last updated
- 13 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/Phase II Open Label Study of the TLR3 Agonist Poly-ICLC as an Adjuvant for NY-ESO-1 Protein Vaccination With or Without Montanide ® ISA-51 VG in Patients With High Risk Melanoma in Complete Clinical Remission
- ClinicalTrials.gov ID
- NCT01079741
- Acronym / sponsor ID
- GCO 13-1391
- Conditions
- Melanoma
- Keywords
- Melanoma, Skin Cancer, Adjuvant Therapy, Oncogenesis, LAGE, Cancer Immunity, Neoplasms, Immunogenicity
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Nina BhardwajUniversity, hospital or other
- Collaborators
- Ludwig Institute for Cancer Research, Oncovir, Inc., Cancer Research Institute, New York City
- Study start
- Sep 2010
- Primary completion
- 11 Mar 2013 (actual)
- Study completion
- 11 Mar 2013 (actual)
- First posted
- 3 Mar 2010 (estimated)
- Results
- Posted 13 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The incidence of melanoma is increasing with an estimated incidence of 59,940 cases and an annual death rate of 8110 in 2007. Although patients diagnosed with early stage disease have an excellent clinical outcome, patients diagnosed with advanced or recurrent disease, continue to have a high mortality rate, even with initial optimal surgical resection. Effective adjuvant strategies are needed to increase the time to progression and to decrease the recurrence rate. Immunotherapy has long been recognized as a potential therapy for melanoma; the goal of adjuvant vaccine therapy is to train the endogenous immune system to recognize and target minimal residual disease.
Detailed description
This is a Phase I open label dose escalation study of the TLR3 agonist Poly-ICLC as an adjuvant for NY-ESO-1 protein vaccination in patients with high risk melanoma in clinical complete remission (cCr), followed by a randomized Phase II component in which patients will be randomized to subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide® ISA-51 VG (Montanide) (Arm B).
Patients with histological confirmed malignant melanoma, AJCC Stages: IIB, IIC, III or IV, who are in complete clinical remission (cCr) but at high risk of disease recurrence, will be eligible for enrollment, regardless of whether antigen expression in the autologous tumor can be demonstrated by either PCR or immunohistochemistry.
Primary Objectives:
- Phase I: To define the safety of subcutaneous vaccination with NY-ESO-1 protein, Montanide and escalating doses of Poly-ICLC.
- Phase II: To evaluate the induction of humoral and T cell (CD4+ and CD8+) immunity to subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given with or without Montanide.
Exploratory analyses:
- Evaluation of primary tumor expression of NY-ESO-1 by IHC or RT-PCR.
- Histologic quantitation of original tumor TILs (tumor infiltrating lymphocytes), CD3+ cells, evaluation of mitotic index and correlation of this data with immunologic response.
- Correlation of NY-ESO-1 specific T cell responses with HLA type
- Investigation of polymorphisms for TLR3 through germline SNP analysis.
- Clinical Outcome (Time to Progression) reported descriptively.
- Skin section analysis of protein/adjuvant treated sites for immune cell infiltration and gene expression analysis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation component | Experimental | Biological: NY-ESO-1 protein; Poly-ICLC; MontanidePhase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen and Montanide will be held constant. |
| Phase II is the randomized component. | Active comparator | Biological: NY-ESO-1 protein; Poly-ICLC; MontanideThe doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histological diagnosis of malignant melanoma, stages IIB-IV in radiologically confirmed cCr without clinical evidence of disease.
- At least 4 weeks since surgery prior to first dosing of study agent.
- Laboratory values within the following limits:
- Patients must have an ECOG performance status of <2 (ECOG criteria published in [67].
- Life expectancy > 6 months.
Key exclusion criteria (14 listed)
- Serious illnesses, e.g., serious infections requiring antibiotics.
- Previous bone marrow or stem cell transplant.
- History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo.
- Metastatic disease to the central nervous system.
- Other malignancy within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ.
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 |
|---|---|---|
| NY-ESO-1 protein; Poly-ICLC; MontanideAlso: Cancer-Testis (CT) antigen expression: NY-ESO-1, Poly ICLC: carboxymethylcellulose, polyinosinic-polycytidylic acid & poly-L-lysine double-stranded RNA, Montanide® ISA-51 VG: mineral oil-based adjuvant; also called (IFA)incomplete Freund's adjuvant.Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen (100µg) and Montanide (1.1mL) will be held constant. Phase II: The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B). | Biological | Dose-escalation component, Phase II is the randomized component. |
Primary outcome
Phase I, Number of Participants With SAE and DLT
Time frame: 52 weeks
Safety measured by number of Serious Adverse Events per the CTEP v4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) and Dose Limiting Toxicity (DLT).
2 secondary outcomes
CD4+ and CD8+ Response
Time frame: Up to 52 weeks
NY-ESO-1 Expression by IHC
Time frame: up to 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Click here for more information about this study: Poly-ICLC as an adjuvant for NY-ESO-1 protein vaccination with or without Montanide ® ISA-51 VG in patients with high risk melanoma in complete clinical remissionLink 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.
Nina Bhardwaj, MD, PhD principal investigator
NYU Langone Health
Anna Pavlick, D.O. principal investigator
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 1/2 study testing NY-ESO-1 protein; Poly-ICLC; Montanide in people with Melanoma, run by Nina Bhardwaj 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 14 inclusion and 14 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 13 Feb 2018. 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 13 Feb 2018). 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?
Phase I, Number of Participants With SAE and DLT (time frame: 52 weeks). 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 13 Feb 2018.