Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma - Full Text View

Sponsor:	University of Pittsburgh
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00390338

Purpose

RATIONALE: Vaccines made from a person's dendritic cells mixed with tumor peptides and proteins may help the body build an effective immune response to kill tumor cells. Infusing the vaccine directly into the lymphatic system may cause a stronger immune response and kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of two dendritic cell vaccines in treating patients with stage III or stage IV melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Biological: PADRE 965.10 Biological: alpha-type-1 polarized dendritic cells Biological: keyhole limpet hemocyanin Biological: therapeutic autologous dendritic cells Other: immunoenzyme technique	Phase I

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine [ Designated as safety issue: Yes ]
Cumulative increase in the sum of specific interferon gamma ELISPOTs against melanoma-specific A2-restricted peptides [ Designated as safety issue: No ]

Secondary Outcome Measures:

Peripheral blood CD8+ and CD4+ T-cell response to HLA-presented melanoma epitopes and autologous tumor cells by interferon gamma and interleukin-5 ELISPOT assay [ Designated as safety issue: No ]
Delayed-type hypersensitivity (DTH) response to treatment [ Designated as safety issue: No ]
DTH response to autologous tumor lysates [ Designated as safety issue: No ]
DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE) [ Designated as safety issue: No ]
Correlation of treatment-associated changes in immune response with clinical outcome [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	October 2006
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Compare the safety of intralymphatic autologous type-1-polarized dendritic cell vaccine vs autologous mature dendritic cell vaccine loaded with antigenic peptides and proteins in patients with stage III or IV melanoma.

Secondary

Determine peripheral blood CD8+ and CD4+ T-cell responses to HLA-presented melanoma epitopes and autologous tumor cells using interferon gamma and interleukin-5 ELISPOT assay.
Compare the delayed-type hypersensitivity (DTH) responses to these regimens and DTH to autologous tumor lysates in these patients.
Compare the DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE) in these patients.
Correlate treatment-associated changes in immune response with clinical outcome.

OUTLINE: This is a randomized, open-label, dose-escalation study. Patients are randomized to 1 of 2 formulations of dendritic cell (DC) vaccines.

Arm I: Patients receive intralymphatic autologous type-1-polarized (by interleukin-1-beta, tumor necrosis factor [TNF] alfa, interferon alfa, poly-I:C, and interferon gamma) DC vaccine that has been loaded with tumor-related peptide antigens (gp100:209-217[210M] peptide, tyrosinase peptide, MART-1:27-35 peptide, MAGE-3/6, and EphA2) and proteins (keyhole limpet hemocyanin [KLH; first course] or pan-DR epitope [PADRE] [second course]) every 6 hours on days 1-4 of weeks 1 and 6.
Arm II: Patients receive intralymphatic autologous mature (by interleukin-1-beta, TNF alfa, interleukin-6, and prostaglandin E_2) DC vaccine that has been loaded with tumor-related peptide antigens and proteins as in arm I every 6 hours on days 1-4 of weeks 1 and 6.

Patients achieving complete response receive 2 more courses of treatment (3 months apart). Patients achieving partial response receive up to 8 more courses of treatment (1 month apart) in the absence of disease progression or unacceptable toxicity.

In each arm, cohorts of 4-7 patients receive escalating doses of DC vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 7 patients experience dose-limiting toxicity.

Blood samples are obtained at baseline and periodically during and after treatment. Samples are examined by immunoenzyme techniques for immunologic measurements.

After completion of study therapy, patients are followed periodically for 10½ years and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed stage III or IVA (M1a) melanoma
- Recurrent and inoperable disease
- Any tumor thickness and any number of lymph nodes involved
- Asymptomatic cutaneous and nodal disease allowed
- Asymptomatic pulmonary metastatic disease (stage IVB, M1b) allowed
No advanced visceral disease, including any symptomatic visceral organ involvement, or disease associated with increased serum lactic dehydrogenase (stage IVC, M1c)
Standard curative or palliative measures do not exist or are no longer effective
Sufficient numbers of monocytes (≥ 20 x 10^6) must be obtained for the preparation of the vaccine
- If an insufficient number of cells is obtained on first venipuncture, a second venipuncture may be performed (not exceeding 550 mL of blood within 8 weeks)
No brain metastases by contrast-enhanced CT scan or MRI
- Prior brain metastases allowed provided they were successfully treated and patient has been asymptomatic for ≥ 3 months
HLA-A2 positive

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Life expectancy ≥ 6 months
Granulocyte count ≥ 2,500/mm³
Lymphocyte count ≥ 1,000/mm³
Platelet count > 100,000/mm³
Creatinine ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Gamma-glutamyl transferase ≤ 2.5 times ULN
Lactic dehydrogenase ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Bilirubin ≤ 1.5 times ULN
No active infection
No sensitivity to drugs that provide local anesthesia
No pain uncontrolled by oral analgesics, including opiates and opiate analogs
No active autoimmune disease
No HIV, hepatitis B, or hepatitis C positivity
Not pregnant or nursing
Fertile patients must use effective contraception
Negative pregnancy test
No other malignancy except for nonmelanoma skin cancers or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Recovered from prior surgery
No radiotherapy, chemotherapy, or immunotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
No antibiotics within the past 7 days
No systemic immunosuppressive agents, including steroids, within the past 4 weeks
- Concurrent maintenance steroids for adrenal insufficiency allowed
No other concurrent anticancer investigational or commercial agents or therapies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390338

Locations

United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
UPMC Cancer Center at Magee-Womens Hospital
Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

University of Pittsburgh

National Cancer Institute (NCI)

Investigators

Study Chair:

John M. Kirkwood, MD

University of Pittsburgh

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000504518, PCI-UPCI-03-118, NCI-7089, PCI-IRB-0409071
Study First Received:	October 18, 2006
Last Updated:	July 9, 2009
ClinicalTrials.gov Identifier:	NCT00390338 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent melanoma
stage III melanoma
stage IV melanoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunologic Factors
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Adjuvants, Immunologic
Keyhole-limpet hemocyanin
Pharmacologic Actions

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas

ClinicalTrials.gov processed this record on February 08, 2010