Melanoma (Skin)Phase 1NCT01176461
Multiple Class I Peptides & Montanide ISA 51 VG w Escalating Doses of Anti-PD-1 ab BMS936558
A Phase 1 study testing MART-1, NY-ESO-1 and gp100:209-217(210M) in people with Melanoma (Skin), run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
This is a pilot phase 1, open-label, single center, multi-dose, dose-escalation study of BMS-936558 in combination with or without a peptide vaccine. The purpose of this study is to test the side effects of an investigational vaccine with an immune booster. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- MART-1, NY-ESO-1 and gp100:209-217(210M)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Aug 2010to 12 Dec 2016
- Phase
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologic diagnosis of unresectable Stage III or IV melanoma. All melanomas regardless of primary site of disease will be allowed
- Measurable unresectable melanoma at least 1 measurable lesion based on Immune-related Response Criteria (irRC)
- Have failed at least 1 chemotherapy regimen for metastatic disease, and have been treated with up to 2 prior chemotherapy regimens
- HLA-A*0201 positive as determined by deoxyribonucleic (DNA) allele-specific polymerase chain reaction (PCR) assay; for cohort 5 after amendment 9 and cohort 6, there is no HLA restriction
- Positive staining of tumor tissue with antibodies to 1 or more of the following: human melanoma black 45 (HMB 45) for gp100, NY-ESO-1, and/or MART-1
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
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- Prior chemotherapy or immunotherapy must have been completed at least 4 weeks before study drug administration, and all adverse events have either returned to baseline or stabilized
- Prior treated brain or meningeal metastases must be without magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration
- Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks before study drug administration. No radiopharmaceuticals (strontium, samarium) within 8 weeks before study drug administration
- Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration
- Completed nitrosourea treatment at least 6 weeks before administration of any study drug
- Prior surgery that required general anesthesia must be completed at least 2 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
- Screening laboratory values must meet the following criteria:
- white blood cells (WBCs) ≥ 2000 cells/ µL
- neutrophils ≥ 1500 cells/ µL
- platelets ≥ 100 x 10^3/ µL
- hemoglobin ≥ 9.0 g/dL
- serum creatinine ≤ 2 mg/dL
- aspartic transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) without, and ≤ 5 x ULN with hepatic metastasis
- alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis
- bilirubin ≤ 2 x ULN (except patients with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL)
- Females of childbearing potential must: Agree to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, double barrier method of condom and spermicidal) for at least 28 days prior to the first dose of any study drug, during the Treatment Period (and Treatment/Follow-up if receiving study drug), and for at least 70 days after the last dose of any study drug; have a negative serum β-human chorionic gonadotropin (β-HCG) at Screening.
- Males must agree to the use of male contraception during the Treatment Period and for at least 180 days after the last dose of any study drug.
- Must have read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained
- Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol
Who cannot join
- History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
- Systemic hypersensitivity to Montanide ISA 51 VG or any vaccine component
- Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast
- Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for patients with vitiligo or resolved childhood asthma/atopy
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Positive tests for hepatitis B virus surface antigen (HBV SAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection
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- Prior therapy with an anti-PD-1, anti-PD-L1, anti-programmed death-ligand-2 (PDL-2), or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (or any other antibody targeting T cell co-stimulation pathways)
- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids
- Underlying medical condition (eg, a condition associated with diarrhea) that, in the Investigator's opinion, would make the administration of either study drug or both study drugs hazardous to the patient or obscure the interpretation of toxicity determination or adverse events
- Pregnant or nursing
- Current participation in another clinical study involving treatment with medications, radiation or surgery, or prior participation in this study
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612-9497
About this study
Official title: A Pilot Trial of a Vaccine Combining Multiple Class I Peptides and Montanide ISA 51 VG With Escalating Doses of Anti-PD-1 Antibody BMS-936558 for Patients With Unresectable Stages III/IV Melanoma
This is a pilot phase 1, open-label, single center, multi-dose, dose-escalation study of BMS-936558 in combination with or without a peptide vaccine.
The purpose of this study is to test the side effects of an investigational vaccine with an immune booster. Investigators also wish to find out its effects on the patient's immune system and whether it will shrink their melanoma.
Read the detailed description
BMS-936558 will be administered as an i.v. infusion, using a volumetric pump with a 0.2 micron in-line filter at the protocol-specified dose(s) and rate.
The vaccine consists of the following peptides: gp100280-288 (288V), and NY-ESO-1157-165 (165V).
NOTE: *Patients in cohorts 1-5 will receive the peptide vaccine, but not those in cohort 6.
Blood samples are collected for pharmacokinetic and immunologic analysis.
After completion of study therapy, patients are followed up periodically for 2 years.
- Conditions
- Melanoma (Skin)
- Being tested
- MART-1, NY-ESO-1, gp100:209-217(210M), gp100:280-288(288V), Montanide ISA 51 VG
- Keywords
- recurrent melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma, stage IV melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MART-1Biological
Also called NSC 709401, peptide vaccine
THIS PEPTIDE REMOVED FROM STUDY ON 1/1/2013. MART-1:26-35(27L) peptide vaccine
NY-ESO-1Biological
Also called NSC 717388, peptide vaccine
NY-ESO-1 peptide vaccine
gp100:209-217(210M)Biological
Also called NSC 683472, peptide vaccine
THIS PEPTIDE REMOVED FROM STUDY ON 1/1/2013. gp100:209-217(210M) peptide vaccine
gp100:280-288(288V)Biological
Also called NSC 683473, peptide vaccine
gp100:280-288(288V) peptide vaccine
Montanide ISA 51 VGDrug
Also called NSC 737063
Administer peptide vaccine emulsions prepared with Montanide® ISA 51 VG by deep subcutaneous injection.
BMS-936558Biological
Also called NSC 748726, Anti PD-1, antibody, MDX-1106
BMS-936558 is a fully human monoclonal antibody (HuMAb) against programmed death-1 (PD-1). Level 1: 1 mg/kg cohort; Level 2: 3 mg/kg cohort; Level 3: 10 mg/kg cohort; Level 4: 3 mg/kg prior ipi gr 0/1/2 cohort; Level 5: 3 mg/kg prior ipi gr 3 cohort; Level 6: 3 mg/kg BMS-936558 (no peptide vaccine; human leukocyte antigen [HLA] unrestricted)
| Study group | Role | What they receive |
|---|---|---|
| A1 - Phase I Dose Escalation | Experimental | Cohorts 1 through 5. Each treatment cycle is comprised of 6 doses of BMS-936558 and 6 peptide vaccines administered every 2 weeks for 12 weeks (cohort 6 has no peptides) (Cycle 1: Weeks 1, 3, 5, 7, 9, and 11; Cycle 2: Weeks 13, 15, 17, 19, 21, and 23) with tumor response assessments at the end of each cycle (during Weeks 12 and 24). Receives: Biological: MART-1; Biological: NY-ESO-1; Biological: gp100:209-217(210M); Biological: gp100:280-288(288V); Drug: Montanide ISA 51 VG; Biological: BMS-936558 |
| A2 - BMS-936558 Without Peptide Vaccine | Active comparator | Cohort 6. Each treatment cycle is comprised of 6 doses of BMS-936558 administered every 2 weeks for 12 weeks (cohort 6 has no peptides) (Cycle 1: Weeks 1, 3, 5, 7, 9, and 11; Cycle 2: Weeks 13, 15, 17, 19, 21, and 23) with tumor response assessments at the end of each cycle (during Weeks 12 and 24). Receives: Biological: BMS-936558 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rate (BORR)
The primary analysis is the BORR as determined using irRC. The BORR will be summarized using descriptive statistics.
Measured: 2 years, 6 months
Secondary outcomes (2)
Time to Response
Time to response for participants with confirmed responses. Response categories: Complete Response (CR), Partial Response (PR) Stable Disease (SD), Progressive Disease (PD); disease control rate (sum of response rate for CR+PR+SD).
Measured: 2 years, 6 months
Duration of Response
Duration of response for participants with confirmed responses. Response categories: Complete Response (CR), Partial Response (PR) Stable Disease (SD), Progressive Disease (PD); disease control rate (sum of response rate for CR+PR+SD).
Measured: 2 years, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2010 (estimated)
- Study start4 Aug 2010
- Primary completion12 Dec 2016
- Study completion12 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Bristol-Myers Squibb, Medarex
- Responsible party
- Sponsor
- Investigators
- Nikhil I. Khushalani, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01176461
- Sponsor's protocol ID
- MCC-15400
- Other IDs
- NCI-P-7997, CA209-006/007, 10-15526-99-01
- Status last verified
- Jan 2023
- First submitted
- 5 Aug 2010
- Last updated
- 18 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Weber JS, Kudchadkar RR, Yu B, Gallenstein D, Horak CE, Inzunza HD, Zhao X, Martinez AJ, Wang W, Gibney G, Kroeger J, Eysmans C, Sarnaik AA, Chen YA. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol. 2013 Dec 1;31(34):4311-8. doi: 10.1200/JCO.2013.51.4802. Epub 2013 Oct 21.
PubMed 24145345
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of a Vaccine Combining Multiple Class I Peptides and Montanide ISA 51 VG With Escalating Doses of Anti-PD-1 Antibody BMS-936558 for Patients With Unresectable Stages III/IV Melanoma
- ClinicalTrials.gov ID
- NCT01176461
- Acronym / sponsor ID
- MCC-15400
- Conditions
- Melanoma (Skin)
- Keywords
- recurrent melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma, stage IV melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Bristol-Myers Squibb, Medarex
- Study start
- 4 Aug 2010 (actual)
- Primary completion
- 12 Dec 2016 (actual)
- Study completion
- 12 Dec 2016 (actual)
- First posted
- 6 Aug 2010 (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 is a pilot phase 1, open-label, single center, multi-dose, dose-escalation study of BMS-936558 in combination with or without a peptide vaccine.
The purpose of this study is to test the side effects of an investigational vaccine with an immune booster. Investigators also wish to find out its effects on the patient's immune system and whether it will shrink their melanoma.
Detailed description
BMS-936558 will be administered as an i.v. infusion, using a volumetric pump with a 0.2 micron in-line filter at the protocol-specified dose(s) and rate.
The vaccine consists of the following peptides: gp100280-288 (288V), and NY-ESO-1157-165 (165V).
NOTE: *Patients in cohorts 1-5 will receive the peptide vaccine, but not those in cohort 6.
Blood samples are collected for pharmacokinetic and immunologic analysis.
After completion of study therapy, patients are followed up periodically for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A1 - Phase I Dose Escalation | Experimental | Biological: MART-1, Biological: NY-ESO-1, Biological: gp100:209-217(210M), Biological: gp100:280-288(288V), Drug: Montanide ISA 51 VG, Biological: BMS-936558Cohorts 1 through 5. Each treatment cycle is comprised of 6 doses of BMS-936558 and 6 peptide vaccines administered every 2 weeks for 12 weeks (cohort 6 has no peptides) (Cycle 1: Weeks 1, 3, 5, 7, 9, and 11; Cycle 2: Weeks 13, 15, 17, 19, 21, and 23) with tumor response assessments at the end of each cycle (during Weeks 12 and 24). |
| A2 - BMS-936558 Without Peptide Vaccine | Active comparator | Biological: BMS-936558Cohort 6. Each treatment cycle is comprised of 6 doses of BMS-936558 administered every 2 weeks for 12 weeks (cohort 6 has no peptides) (Cycle 1: Weeks 1, 3, 5, 7, 9, and 11; Cycle 2: Weeks 13, 15, 17, 19, 21, and 23) with tumor response assessments at the end of each cycle (during Weeks 12 and 24). |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- Histologic diagnosis of unresectable Stage III or IV melanoma. All melanomas regardless of primary site of disease will be allowed
- Measurable unresectable melanoma at least 1 measurable lesion based on Immune-related Response Criteria (irRC)
- Have failed at least 1 chemotherapy regimen for metastatic disease, and have been treated with up to 2 prior chemotherapy regimens
- HLA-A*0201 positive as determined by deoxyribonucleic (DNA) allele-specific polymerase chain reaction (PCR) assay; for cohort 5 after amendment 9 and cohort 6, there is no HLA restriction
- Positive staining of tumor tissue with antibodies to 1 or more of the following: human melanoma black 45 (HMB 45) for gp100, NY-ESO-1, and/or MART-1
Key exclusion criteria (11 listed)
- History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
- Systemic hypersensitivity to Montanide ISA 51 VG or any vaccine component
- Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast
- Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for patients with vitiligo or resolved childhood asthma/atopy
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
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 |
|---|---|---|
| MART-1Also: NSC 709401, peptide vaccineTHIS PEPTIDE REMOVED FROM STUDY ON 1/1/2013. MART-1:26-35(27L) peptide vaccine | Biological | A1 - Phase I Dose Escalation |
| NY-ESO-1Also: NSC 717388, peptide vaccineNY-ESO-1 peptide vaccine | Biological | A1 - Phase I Dose Escalation |
| gp100:209-217(210M)Also: NSC 683472, peptide vaccineTHIS PEPTIDE REMOVED FROM STUDY ON 1/1/2013. gp100:209-217(210M) peptide vaccine | Biological | A1 - Phase I Dose Escalation |
| gp100:280-288(288V)Also: NSC 683473, peptide vaccinegp100:280-288(288V) peptide vaccine | Biological | A1 - Phase I Dose Escalation |
| Montanide ISA 51 VGAlso: NSC 737063Administer peptide vaccine emulsions prepared with Montanide® ISA 51 VG by deep subcutaneous injection. | Drug | A1 - Phase I Dose Escalation |
| BMS-936558Also: NSC 748726, Anti PD-1, antibody, MDX-1106BMS-936558 is a fully human monoclonal antibody (HuMAb) against programmed death-1 (PD-1). Level 1: 1 mg/kg cohort; Level 2: 3 mg/kg cohort; Level 3: 10 mg/kg cohort; Level 4: 3 mg/kg prior ipi gr 0/1/2 cohort; Level 5: 3 mg/kg prior ipi gr 3 cohort; Level 6: 3 mg/kg BMS-936558 (no peptide vaccine; human leukocyte antigen [HLA] unrestricted) | Biological | A1 - Phase I Dose Escalation, A2 - BMS-936558 Without Peptide Vaccine |
Primary outcome
Best Overall Response Rate (BORR)
Time frame: 2 years, 6 months
The primary analysis is the BORR as determined using irRC. The BORR will be summarized using descriptive statistics.
2 secondary outcomes
Time to Response
Time frame: 2 years, 6 months
Duration of Response
Time frame: 2 years, 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
- Derived from this study: PubMed 24145345Weber JS, Kudchadkar RR, Yu B, Gallenstein D, Horak CE, Inzunza HD, Zhao X, Martinez AJ, Wang W, Gibney G, Kroeger J, Eysmans C, Sarnaik AA, Chen YA. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol. 2013 Dec 1;31(34):4311-8. doi: 10.1200/JCO.2013.51.4802. Epub 2013 Oct 21.
- Moffitt Cancer Center Clinical Trials 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.
Nikhil I. Khushalani, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 MART-1, NY-ESO-1 and gp100:209-217(210M) in people with Melanoma (Skin), run by H. Lee Moffitt Cancer Center and Research Institute 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 25 inclusion and 11 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 18 Jan 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?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Best Overall Response Rate (BORR) (time frame: 2 years, 6 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 NCT01176461, 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 18 Jan 2023.