Clinical trial NCT00070070: Vaccine Therapy in Treating Patients With Transitional Cell Carcinomas
Official title: NY-ESO-1 Protein Immunization of Post-Cystectomy or Post-Nephroureterectomy Patients With Transitional Cell Carcinomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Transitional Cell Carcinoma
Keywords: Bladder cancer
Renal pelvis cancer
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-07
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This study was open-label, and eligible patients were sequentially entered at the time they presented in clinic. Patients were sequentially assigned to one of four groups according to HLA-A2 characteristic and previous Bacille Calmette Guerin (BCG) therapy.
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Biological therapies, such as Bacille Calmette Guerin (BCG) and sargramostim (GM-CSF), use different ways to stimulate the immune system and stop tumor cells from growing. Combining vaccine therapy with biological therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects of giving vaccine therapy together with BCG and sargramostim in treating patients who have undergone cystectomy for transitional cell carcinomas.

Detailed description: OBJECTIVES:

* Determine the safety and tolerability of NY-ESO-1 peptide vaccine, Bacille Calmette Guerin (BCG), and sargramostim (GM-CSF) in post-cystectomy patients with transitional cell carcinoma of the bladder expressing NY-ESO-1 or LAGE-1 antigen.
* Determine the immunological profile (NY-ESO-1 antibody, CD8+ cells, and delayed-type hypersensitivity) induced by this regimen in these patients.

OUTLINE: This is an open-label, pilot study.

Patients receive NY-ESO-1 protein vaccine mixed with BCG intradermally (ID) once weekly on weeks 1 and 2. Patients then receive NY-ESO-1 protein mixed with sargramostim (GM-CSF) ID once weekly on day 2 of weeks 3-6. Patients also receive GM-CSF subcutaneously alone on days 1, 3, 4, and 5 of weeks 3-6.

Eligibility criteria: Inclusion Criteria

1. Post-cystectomy or post-nephroureterectomy patients with histological confirmation of transitional cell carcinoma.
2. Patients must have had a cystectomy or nephroureterectomy within 16 weeks of first vaccination.
3. At least 4 weeks since surgery prior to receiving the first vaccination.
4. Radiological imaging to document no evidence of disease within one month prior to receiving the first vaccination.
5. Laboratory values within the following limits:

Hemoglobin ≥ 10.0 g/dL Neutrophil count ≥ 1.5 x 10E9/L Lymphocyte count ≥ 0.5 x 10E9/L Platelet count ≥ 100 x 10E9/L Serum creatinine ≤ 1.8 mg/dL Serum bilirubin ≤ 2mg/dL Serum aspartate aminotransferase (AST) (SGOT) \<2.5 X ULN Serum alanine aminotransaminase (ALT) (SGPT) \<2.5 X ULN 6. Performance status ≤ 2 (ECOG Scale) and life expectancy ≥ 3 months. 7. Age ≥ 18 years. 8. Fertile patients must have a negative urine or serum pregnancy test and use barrier method contraception before, during and for 6 months after protocol therapy. Patients are encouraged to continue barrier method contraception for two years or longer after treatment.

9. Able and willing to give valid written informed consent. Exclusion Criteria

1. Clinically significant heart disease (NYHA Class III or IV).
2. Presence of severe reaction to PPD (purified protein derivative) (\>40 mm induration).
3. Prior malignancy within 5 years that has been treated with extensive chemotherapy / radiation therapy and have the potential for immune dysfunction or who have evidence of metastasis at the time of registration.
4. Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, antibiotic use within 5 days of treatment.
5. Previous bone marrow or stem cell transplant.
6. History of immunodeficiency disease or autoimmune disease.
7. Known positive HIV test.
8. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
9. Concomitant treatment with corticosteroids (within 30 days of enrollment and during treatment), antihistaminic drugs, or nonsteroidal anti-inflammatory drugs (unless chronically used in low doses for prevention of an acute cardiovascular event or pain control). Topical or inhalational steroids are permitted.
10. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
11. Mental disorders that may compromise the ability to give informed consent and comply with the requirements of the study.
12. Lack of availability of the patient for immunological and clinical follow-up assessment.
13. Positive urine or serum pregnancy test.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities
timeFrame: up to 12 weeks
Secondary outcomes:
measure: Number of Patients Developing NY-ESO-1 Antibodies After Treatment
timeFrame: up to 12 weeks
measure: Number of Patients With CD4+ and CD8+ T-cell Responses.
timeFrame: up to 12 weeks
measure: Delayed-type Hypersensitivity (DTH) as Measured by the Number of Participants With Induration and/or Redness at Each Timepoint
timeFrame: up to 8 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Dean F. Bajorin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Harry W. Herr, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sharma P, Bajorin DF, Jungbluth AA, Herr H, Old LJ, Gnjatic S. Immune responses detected in urothelial carcinoma patients after vaccination with NY-ESO-1 protein plus BCG and GM-CSF. J Immunother. 2008 Nov-Dec;31(9):849-57. doi: 10.1097/CJI.0b013e3181891574.