Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Treatment	Completed	18 and over	Other	LUD2003-022;NYU05-120;CUMC9147 NCT00299728

Trial Description

Summary

This is a phase I, open-label, randomized study of NY-ESO-l protein with immune adjuvants CpG 7909 and Montanide® ISA-51 and NY-ESO-l protein 400µg with immune adjuvants CpG 7909 and Montanide® ISA-51 in patients with tumors that often express NY-ESO-1.

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

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

The primary objective of the study is to define the safety.

Secondarily, the study will evaluate whether patients develop a specific immunologic response to the NY-ESO-1 protein. Blood samples will 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, will be determined by FACS analysis. In addition, humoral immunity will be determined by the presence of NY-ESO-1 specific antibodies which will be assessed in all patients by ELISA.

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

Further Study Information

You will receive an investigational (research) cancer vaccine every 3 weeks for a total of 4 treatments. It is given by injection underneath your 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 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.) There is a 50:50 chance that you will receive the lower versus the higher dose. At this time we have no way of knowing whether there will be any real difference in the effects between these doses. In either case you will be receiving the NY-ESO-1 protein. In all studies to date, only the 100 µg dose has been used. There is no reason to think that the higher dose will be toxic, nor is there any reason at this time to think that the higher dose will be more effective at the immunological level, although it may be, which is the reason for comparing the effects of these two doses of protein.

The NY-ESO-1 protein vaccine is mixed with 2 substances, called adjuvants (the full names are: CPG 7909 and Montanide ISA-51). 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 will be performed as an outpatient.

Eligibility Criteria

Inclusion Criteria:

Patients will be eligible for enrollment if they fulfill the following 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 l09/L

• Lymphocyte count > Lower limit of institutional normal

• Platelet count > 80 x l09/L

• Serum creatine < 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 (see Section 12.2)

Exclusion Criteria:

Patients will be excluded from the study if they fulfill any of the following 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. (See also Section 6.7 for restrictions/recommendations on 'Ancillary Therapy'.)

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.

Trial Contact Information

Trial Lead Organizations/Sponsors

Ludwig Institute for Cancer Research

Nina Bhardwaj

Principal Investigator

Sylvia Adams, MD

Study Director

Gregory Mears, MD

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00299728
Information obtained from ClinicalTrials.gov on March 18, 2009