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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01810016




Registration number
NCT01810016
Ethics application status
Date submitted
8/03/2013
Date registered
13/03/2013
Date last updated
30/11/2018

Titles & IDs
Public title
NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma
Scientific title
Phase I Study of NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma, for Whom Treatment With Ipilimumab is Indicated
Secondary ID [1] 0 0
LUD2012-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable or Metastatic Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Ipilimumab
Other interventions - NY-ESO-1 Protein Vaccine
Other interventions - NY-ESO-1 OLP4 Vaccine with Poly-ICLC and Montanide
Other interventions - NY-ESO-1 OLP4 Vaccine with Poly-ICLC

Experimental: Arm A - Ipilimumab (IV) followed by NY-ESO-1 recombinant protein mixed with Poly-ICLC and Montanide (SC) every 3 weeks for 4 doses.

Experimental: Arm B - Ipilimumab (IV) followed by NY-ESO-1 OLP4 mixed with Poly-ICLC and Montanide (SC) every 3 weeks for 4 doses.

Experimental: Arm C - Ipilimumab (IV) followed by NY-ESO-1 OLP4 mixed with Poly-ICLC (SC) every 3 weeks for 4 doses.


Other interventions: Ipilimumab
Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses.

Other interventions: NY-ESO-1 Protein Vaccine
NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.

Other interventions: NY-ESO-1 OLP4 Vaccine with Poly-ICLC and Montanide
NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.

Other interventions: NY-ESO-1 OLP4 Vaccine with Poly-ICLC
NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Patients With Treatment-emergent Adverse Events - Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity (DLT) was defined as any = Grade 3 hematologic or non-hematologic toxicity that was definitely, probably, or possibly related to the administration of the NY-ESO-1 vaccine or as any toxicity that was definitely, probably, or possibly related to ipilimumab and required permanent discontinuation of ipilimumab in accordance with local prescribing information. DLT assessments were based on the combination of all vaccine components, not on the components individually.
Timepoint [1] 0 0
Continuously for up to 6 months
Secondary outcome [1] 0 0
Number of Patients With Immune-related Tumor Response at the Last Assessment - Immune-related tumor response was evaluated using the imaging techniques considered appropriate by the Investigators at Baseline, Week 13, and at the end of the study (Week 20 ± 1 week). Tumor response was designated according to the immune-related Response Criteria (irRC) (Wolchok et al. Clin Cancer Res 2009;15:7412-20) into the following categories: immune-related complete response (irCR) requires disappearance of all lesions in two consecutive observations not less than 4 weeks apart; immune-related partial response (irPR) requires = 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; immune-related stable disease (irSD) is assigned when neither a 50% decrease from baseline tumor burden nor a 25% increase in tumor burden from nadir can be established; immune-related progressive disease (irPD) requires a = 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart.
Timepoint [1] 0 0
Up to 5 months

Eligibility
Key inclusion criteria
1. Patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab
was indicated as per ipilimumab/Yervoy® package insert (applicable for United States
[US] sites) or product information (applicable for Australia site).

2. Radiologically measurable disease by irRC.

3. Tumor expression of NY-ESO-1 or LAGE-1 antigen by immunohistochemistry or reverse
transcriptase-polymerase chain reaction (RT-PCR), or evidence of seropositivity to
NY-ESO-1 or LAGE-1.

4. Willingness to provide at least one pre-and post-vaccination tumor biopsy sample.

5. Expected survival of at least 4 months.

6. At the time of Day 1 of the study, patients must have been at least 3 weeks since
surgery.

7. At the time of Day 1 of the study, patients with brain metastases must have been
asymptomatic and:

- at least 8 weeks without tumor progression after any whole brain radiotherapy;

- at least 4 weeks since craniotomy and resection or stereotactic radiosurgery;

- at least 3 weeks without new brain metastases as evidenced by magnetic resonance
imaging (MRI).

8. Eastern Cooperative Oncology Group performance status of 0 to 2.

9. Laboratory parameters for vital functions must have been in the normal range.
Laboratory abnormalities that were not clinically significant were generally
permitted, except for the following laboratory parameters, which must have been within
the ranges specified:

- hemoglobin: = 10 g/dL;

- neutrophil count: = 1.5 x 10^9/L;

- lymphocyte count: = lower limit of normal (LLN);

- platelet count: = 80 x 10^9/L;

- serum creatinine: = 2 mg/dL;

- serum bilirubin: = 2 x upper limit of normal (ULN);

- aspartate aminotransferase (AST)/alanine aminotransferase (ALT): = 2 x ULN.

10. Had been informed of other treatment options.

11. Age = 18 years.

12. Able and willing to give valid written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any contraindications for ipilimumab/Yervoy® as per package insert (applicable for US
sites) or product information (applicable for Australia site).

2. Prior exposure to NY-ESO-1 vaccine.

3. Active autoimmune disease, symptoms or conditions except for vitiligo, type I
diabetes, treated thyroiditis, asymptomatic laboratory evidence of autoimmune disease
(e.g., +antinuclear antibody [ANA], +rheumatoid factor [RF], antithyroglobulin
antibodies), or mild arthritis requiring no therapy or manageable with nonsteroidal
anti-inflammatory drugs (NSAIDs).

4. Unresolved immune-related adverse events following prior biological therapy.

5. Systemic treatment with high-dose corticosteroids (greater than prednisone 10 mg daily
or equivalent).

6. Treatment with protocol-specified non-permitted concomitant therapies.

7. Metastatic disease to the central nervous system for which other therapeutic options,
including radiotherapy, may have been available.

8. Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or
transient ischemic attack, chest pain or shortness of breath with activity, or other
heart conditions being treated by a doctor.

9. Other malignancy within 3 years prior to entry into the study, except for treated
non-melanoma skin cancer and cervical carcinoma in situ.

10. Known immunodeficiency or human immunodeficiency virus positivity, active Hepatitis B
or active Hepatitis C.

11. History of severe allergic reactions to vaccines or unknown allergens.

12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
disorders).

13. Participation in any other clinical trial involving another investigational agent
within 4 weeks prior to Day 1 of the study.

14. Mental impairment that may have compromised the ability to give informed consent and
comply with the requirements of the study.

15. Lack of availability for immunological and clinical follow-up assessments.

16. Women who were breast feeding or pregnant as evidenced by positive serum pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
[HCG]) done within 14 days prior to first dosing and urine test within 72 hours prior
to first dosing.

17. Women of childbearing potential not using a medically acceptable means of
contraception for the duration of the study.

18. Any condition that, in the clinical judgment of the treating physician, was likely to
prevent the patient from complying with any aspect of the protocol or that may have
put the patient at unacceptable risk.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Health, Ludwig Oncology Unit - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
United States of America
State/province [3] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Other
Name
Ludwig Institute for Cancer Research
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cancer Research Institute, NY, USA
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This was a Phase 1, open-label, non-randomized study of the combination of NY-ESO-1 plus
ipilimumab in patients with unresectable or metastatic melanoma for whom treatment with
ipilimumab was indicated. Patients must have had evidence of NY-ESO-1 or LAGE-1 tumor
positivity and radiologically measurable disease by the immune-related Response Criteria
(irRC). Primary study objectives were to determine the safety and tolerability of the
combination and to evaluate humoral and cellular immune response. Secondary objectives were
to evaluate tumor response and immunological changes in the tumor microenvironment.
Trial website
https://clinicaltrials.gov/show/NCT01810016
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael A Postow, MD
Address 0 0
Memorial Sloan Kettering Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01810016