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Transitional Cell CarcinomaPhase 1NCT00070070

Vaccine Therapy in Treating Patients With Transitional Cell Carcinomas

A Phase 1 study testing TICE®-strain BCG, NY-ESO-1 protein and sargramostim in people with Transitional Cell Carcinoma, run by Ludwig Institute for Cancer Research at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Transitional Cell Carcinoma
What is being tested?
TICE®-strain BCG, NY-ESO-1 protein and sargramostim
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
28 Oct 2003to 30 Sep 2013
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Post-cystectomy or post-nephroureterectomy patients with histological confirmation of transitional cell carcinoma.
  • Patients must have had a cystectomy or nephroureterectomy within 16 weeks of first vaccination.
  • At least 4 weeks since surgery prior to receiving the first vaccination.
  • Radiological imaging to document no evidence of disease within one month prior to receiving the first vaccination.
  • 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.
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  • 9. Able and willing to give valid written informed consent. Exclusion Criteria
  • Clinically significant heart disease (NYHA Class III or IV).
  • Presence of severe reaction to PPD (purified protein derivative) (>40 mm induration).
  • 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.
  • Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, antibiotic use within 5 days of treatment.
  • Previous bone marrow or stem cell transplant.
  • History of immunodeficiency disease or autoimmune disease.
  • Known positive HIV test.
  • Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
  • 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.
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
  • Mental disorders that may compromise the ability to give informed consent and comply with the requirements of the study.
  • Lack of availability of the patient for immunological and clinical follow-up assessment.
  • Positive urine or serum pregnancy test.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

Other trials in United States

About this study

Official title: NY-ESO-1 Protein Immunization of Post-Cystectomy or Post-Nephroureterectomy Patients With Transitional Cell Carcinomas

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.

Read the 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.

Being tested
TICE®-strain BCG, NY-ESO-1 protein, sargramostim
Keywords
Bladder cancer, Renal pelvis cancer
Medical subject headings
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TICE®-strain BCGBiological

    Also called BCG Live, Tice® BCG, BCG Vaccine

  • NY-ESO-1 proteinBiological

  • sargramostimBiological

    Also called GM-CSF

Study groups in NCT00070070
Study groupRoleWhat they receive
Cohort 1ExperimentalHLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Receives: Biological: TICE®-strain BCG; Biological: NY-ESO-1 protein; Biological: sargramostim
Cohort 2ExperimentalHLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Receives: Biological: TICE®-strain BCG; Biological: NY-ESO-1 protein; Biological: sargramostim
Cohort 3ExperimentalHLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Receives: Biological: TICE®-strain BCG; Biological: NY-ESO-1 protein; Biological: sargramostim
Cohort 4ExperimentalHLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 106 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 105 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Receives: Biological: TICE®-strain BCG; Biological: NY-ESO-1 protein; Biological: sargramostim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose Limiting Toxicities

    All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTCAE) (Version 3.0). A Dose limiting toxicity (DLT) was defined as:

    • ≥ Grade 2 autoimmune phenomena
    • Asymptomatic bronchospasm or generalized urticaria
    • ≥ Grade 3 hematological and non hematological toxicities. To be dose limiting, an adverse event must have been definitely, probably, or possibly related to the administration of the study treatment. Patients who experienced a DLT were removed from study.

    Measured: up to 12 weeks

Secondary outcomes (3)
  1. Number of Patients Developing NY-ESO-1 Antibodies After Treatment

    Blood samples were obtained at baseline, and at weeks 2, 4, 6, 8 and 12 for the assessment of NY-ESO-1 and LAGE-1 specific antibodies by enzyme-linked immunosorbent assay (ELISA).

    Measured: up to 12 weeks

  2. Number of Patients With CD4+ and CD8+ T-cell Responses.

    Blood samples were obtained at baseline, and at weeks 2, 4, 6, 8 and 12 for the assessment of NY-ESO-1 specific T-cell responses by ELISPOT. T-cell responses were monitored after in vitro sensitization with either overlapping peptides from NY-ESO-1 or recombinant adenovirus encoding NY-ESO-1 (adeno-NY-ESO-1), and with control peptides or recombinant vectors encoding Influenza-derived proteins.

    Measured: up to 12 weeks

  3. Delayed-type Hypersensitivity (DTH) as Measured by the Number of Participants With Induration and/or Redness at Each Timepoint

    NY-ESO-1-specific DTH skin reaction was measured at baseline and weeks 3 and 8.The peptide solution (10 μg peptide in 0.1ml normal saline) was injected intradermally at a separate site from the vaccination to give a visible and palpable skin depot. Assessment of DTH reactions was performed 48 h after injection.

    The extent and intensity of DTH reactions was documented by measuring visible "redness", palpable "induration" and other signs of local skin irritation or necrosis.

    Measured: up to 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2003 (estimated)
  2. Study start28 Oct 2003
  3. Primary completion3 Jan 2006
  4. Study completion30 Sep 2013

Resources

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
Sequential
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.
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00070070
Sponsor's protocol ID
LUD2002-004
Other IDs
MSKCC-03047, LUDWIG-LUD2002-004, CDR0000329920
Status last verified
Oct 2022
First submitted
3 Oct 2003
Last updated
12 Oct 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 18833002

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TICE®-strain BCG, NY-ESO-1 protein and sargramostim in people with Transitional Cell Carcinoma, run by Ludwig Institute for Cancer Research 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 20 inclusion and 0 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 12 Oct 2022. 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?

Yes. Results are posted in the registry (first posted 8 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Dose Limiting Toxicities (time frame: up to 12 weeks). 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 NCT00070070, 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 12 Oct 2022.

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