NY-ESO-1 Protein With Montanide and CpG 7909 as Cancer Vaccine in Several Tumors

NCT ID: NCT00299728

Last Updated: 2022-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-21
• Study Completion Date: 2014-01-10

Brief Summary

This is a Phase I, open-label, randomized study of NY-ESO-l protein with immune adjuvants CpG 7909 and Montanide ISA-51 VG in patients with tumors that often express NY-ESO-1.

The vaccinations was to be administered subcutaneously every 3 weeks for 4 doses.

Patients with any malignancy that is known to frequently express NY-ESO-1 were eligible, regardless of whether antigen expression in the autologous tumor could be demonstrated or not by either PCR or immunohistochemistry.

The primary objective of the study was to define safety.

Secondarily, the study was to evaluate whether patients developed a specific immunologic response to the NY-ESO-1 protein. Blood samples were to be obtained at baseline, prior to each vaccination, one week after each vaccination, and at the last study visit for the assessment of NY-ESO-1-specific CD4+ and CD8+ T cells. Cytokine secretion by NY-ESO-1-specific CD8+ and CD4+ T cells, as a measure of T cell activation, was to be determined by FACS analysis. In addition, humoral immunity was to be determined by the presence of NY-ESO-1-specific antibodies which were to be assessed in all patients by ELISA.

Disease status was to be assessed at baseline and 2-4 weeks after the fourth vaccination in patients with evaluable (measurable and non-measurable) disease.

Detailed Description

Subjects were to receive an investigational (research) cancer vaccine every 3 weeks for a total of 4 treatments. It was given by injection underneath the skin in an extremity (leg or arm). A vaccine is a compound designed to strengthen the immune system (the cells and substances that protect the body from infection and foreign matter) to fight an illness such as infections or cancer. This vaccine is called NY-ESO-1 protein. NY-ESO-1 protein (an antigen, which is a compound that is recognized by the immune system) is found in many cancers. Proteins such as NY-ESO-1 and their fragments are the targets the immune system needs to recognize cancer cells. If the immune system can recognize these antigens (foreign substances) it may be able to kill the cells that carry them. NY-ESO-1 can be found at different stages of cancers, and is likely to be expressed (shown) at some point in the lifecycle of these types of cancer (that are eligible for this study). Therefore this study tries to boost (strengthen) the immune system toward NY-ESO-1 protein regardless of whether it is found in your tumor or not.

Since we do not know whether different doses of the NY-ESO-1 protein may result in varying degrees of immune stimulation, we will be randomizing (that is, at the flip of a coin or, in other words, by chance). You may receive either the lower dose of NY-ESO-1 protein (100 µg) or the higher dose (400 µg).

The NY-ESO-1 protein vaccine was to be mixed with 2 substances, called adjuvants (the full names are: CPG 7909 and Montanide ISA-51 VG). Adjuvants are substances to increase the vaccine's ability to stimulate the immune system. By adding two adjuvants to the vaccine, it is hoped that the boosting of the immune system will be especially effective.

It is important to understand, that vaccines are only experimental (investigational, research) for the treatment of cancer. They are not approved by the Food and Drug Administration (FDA) as treatment. Therefore they are only offered in clinical trials.

All tests and treatments were performed as an outpatient.

Conditions

Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A; 100 μg NY-ESO-1 protein co-mixed with CpG 7909 and Montanide ISA-51 VG

100 μg NY-ESO-1 protein co-mixed with 2.5 mg CpG 7909 and 1.25 mL Montanide ISA-51 VG. The vaccine was administered subcutaneously every 3 weeks for a total of 4 doses (study weeks 1, 4, 7 and 10).

Group Type: EXPERIMENTAL

NY-ESO-1 Protein Vaccine

Intervention Type: BIOLOGICAL

NY-ESO-1 recombinant protein mixed with CpG 7909 and Montanide ISA-51 VG

Arm B; 400 μg NY-ESO-1 protein co-mixed with CpG 7909 and Montanide ISA-51 VG

400 μg NY-ESO-1 protein co-mixed with 2.5 mg CpG 7909 and 1.25 mL Montanide ISA-51 VG. The vaccine was administered subcutaneously every 3 weeks for a total of 4 doses (study weeks 1, 4, 7 and 10).

Group Type: EXPERIMENTAL

NY-ESO-1 Protein Vaccine

Intervention Type: BIOLOGICAL

NY-ESO-1 recombinant protein mixed with CpG 7909 and Montanide ISA-51 VG

Interventions

NY-ESO-1 Protein Vaccine

NY-ESO-1 recombinant protein mixed with CpG 7909 and Montanide ISA-51 VG

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Histological diagnosis of hepatocellular carcinoma, bladder cancer, breast cancer, non-small lung cancer (NSCLC), melanoma, sarcoma, prostate cancer, esophageal cancer, or ovarian cancer, independent of NY-ESO-1 expression in a tumor biopsy.

or

Histological diagnosis of other types of cancers, provided NY-ESO-1 or LAGE-1 expression can be shown in a tumor biopsy.

2. At least 4 weeks since surgery prior to first dosing of study agent.

3. Laboratory values within the following limits:

• Hemoglobin ≥ 11.0 g/dL
• Neutrophil count ≥ 1.5 x l0^9/L
• Lymphocyte count ≥ lower limit of institutional normal
• Platelet count ≥ 80 x l0^9/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

4. Patients must have a Karnofsky performance status of ≥70%.

5. Life expectancy ≥ 6 months.

6. Age ≥ 18 years.

7. Able and willing to give witnessed, written informed consent for participation in the trial.

Exclusion Criteria

1. Clinically significant heart disease (i.e. NYHA class 3 congestive heart failure; myocardial infarction within the past six months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).

2. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.

3. Previous bone marrow or stem cell transplant.

4. History of immunodeficiency disease or autoimmune disease except vitiligo.

5. Metastatic disease to the central nervous system, unless treated and stable.

6. 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.

7. Known HIV, Hepatitis B or Hepatitis C positivity.

8. Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of study agent (6 weeks for nitrosoureas).

9. Concomitant treatment with steroids. Topical or inhalational steroids are permitted.

10. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.

11. Pregnancy or lactation.

12. Women of childbearing potential not using a medically acceptable means of contraception.

13. Psychiatric or addictive disorders that may compromise the ability to give informed consent.

14. Lack of availability of the patient for immunological and clinical follow-up assessment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NYU Langone Health

OTHER

Sponsor Role: collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nina Bhardwaj, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Sylvia Adams, MD

Role: STUDY_DIRECTOR

NYU Langone Health

Gregory Mears, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

NYU Clinical Cancer Center

New York, New York, United States

NY Presbyterian- Columbia

New York, New York, United States

Countries

United States

References

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

Reference Type: BACKGROUND

PMID: 10655437 (View on PubMed)

Valmori D, Souleimanian NE, Tosello V, Bhardwaj N, Adams S, O'Neill D, Pavlick A, Escalon JB, Cruz CM, Angiulli A, Angiulli F, Mears G, Vogel SM, Pan L, Jungbluth AA, Hoffmann EW, Venhaus R, Ritter G, Old LJ, Ayyoub M. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8947-52. doi: 10.1073/pnas.0703395104. Epub 2007 May 15.

Reference Type: RESULT

PMID: 17517626 (View on PubMed)

Other Identifiers

LUD2003-022;NYU05-120;CUMC9147

Identifier Type: -

Identifier Source: org_study_id