Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

gene expression analysis

mutation analysis

diagnostic laboratory biomarker analysis

immunohistochemistry staining method

sentinel lymph node biopsy

Julia Newton Bishop, MD

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help the study of cancer in the future.

PURPOSE: This laboratory study is looking at tumor tissue samples from patients with melanoma who have undergone sentinel lymph node biopsy.

OBJECTIVES:

* Develop a predictive model for sentinel lymph node biopsy positivity in patients with melanoma who have undergone sentinel lymph node biopsy.
* Develop a survival model for relapse based on sentinel lymph node biopsy positivity.
* Assess the genetic determinants in primary melanomas that predict a metastatic phenotype and thereby improve understanding of the biology of the metastases in melanoma.

OUTLINE: This is a retrospective, case-controlled, multicenter study. Patients are stratified according to Breslow thickness of the tumor (0.75-1.50 mm vs 1.51- 4 mm vs \> 4 mm) and gender.

Archived tumor tissue is analyzed by immunohistochemistry (IHC) for AP2, vascular endothelial growth factor, MMP 2, MCM4, and others, if feasible. Sentinel node biopsies are analyzed by IHC for CD31, LYVE-1, and D2-40 expression. RNA and DNA are also extracted for genetic expression studies and mutation analysis (e.g., BRAF, NRAS, PTEN, CDKN2A).

Patient data related to relapse and recurrence is collected, if available.

Peer reviewed and funded or endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study.

Studying Tumor Tissue Samples From Patients With Melanoma Who Have Undergone Sentinel Lymph Node Biopsy

A Retrospective Case-Control Study of Melanoma Patients Who Have Undergone Sentinel Lymph Node Biopsy

Leeds Cancer Centre at St. James's University Hospital

All Drugs and Chemicals

Vaccines

Freund's Adjuvant

Patients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory biomarker analysis.

Patients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory biomarker analysis.

HPV 16 E7:12-20

gp100:209-217(210M)

laboratory biomarker analysis

Walter J. Urba, MD, PhD

This randomized pilot phase II trial studies how well vaccine therapy works in treating human leukocyte antigen class 1 histocompatibility, A-2 (HLA-A2) positive patients with melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells.

PRIMARY OBJECTIVES:

I. To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217\[210M\] peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20 peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients who present with a primary melanoma \> 1 mm thick.

II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and the unmodified parental glycoprotein 100 (gp100) peptide.

III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1 restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20.

IV. To determine whether analysis of antigen-specific T-cells using specific HLA-A2/peptide tetramers is an effective method for monitoring the immune response of patients undergoing peptide vaccination and to compare it to enzyme-linked immunosorbent spot (ELISPOT), limiting dilution analysis (LDA) and measurement of intracellular cytokine production (fastimmune).

V. To determine whether there is a difference between the induction of primary peptide-specific T-cell immune responses to the self gp100 peptide versus the foreign E7 peptide.

VI. To compare the immune response induced by vaccinating every 2 weeks for 6 months (a total of 13 vaccinations) vs. every 3 weeks for 6 months (a total of 9 vaccinations).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant subcutaneously (SC) every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

In both arms, patients undergo sentinel lymph node biopsy approximately 10 days after the second vaccination. Patients with positive lymph nodes undergo complete lymph node dissection and resume vaccinations.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.

Vaccine Therapy in Treating HLA-A2 Positive Patients With Melanoma

A Randomized Phase II Trial to Determine the Immune Response to a Mutated gp100 Melanoma Peptide (209-2M) Vaccine in HLA-A2 Positive Patients With a &gt;1mm Melanoma on Initial Biopsy

Frequency measures obtained from each assay will be transformed to (common) logs for purposes of analysis. Repeated measures analyses will be performed on longitudinal data to assess patients' immune response profiles over time. Comparability of assay methods will be assessed with correlation analyses, regression analyses, standard parametric and nonparametric tests, and agreement methods.

Pre- and post-immunization T-cell immunity to g209-2M peptide, to HPV16E7 peptide, and to a negative control HLA-A2 HIV peptide (pol) were assessed using HLA-A2/peptide tetramer-specific binding analysis. Within-subject analyses were performed to determine differences between pre- and postimmunization responses to the g209 -2M and HPV peptides and to the negative control HIV peptide after completion of 6 months of vaccination. Pre- versus postimmunization response differences were used as criterion measures in between-group (among subjects) analyses.

National Cancer Institute (NCI)

Patients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

HPV 16 E7:12-20 peptide vaccine: Given SC

gp100:209-217(210M) peptide vaccine: Given SC

laboratory biomarker analysis: Correlative studies

Arm A (Every 2 Weeks)

Patients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

HPV 16 E7:12-20 peptide vaccine: Given SC

gp100:209-217(210M) peptide vaccine: Given SC

laboratory biomarker analysis: Correlative studies

Arm B (Every 3 Weeks)

Total

Age, Categorical

Gender

Walter J. Urba, MD, PhD; Physician Director of Research

pre-treatment %gp100 g209-2M-specific T cells

Post-treatment % gp100 g209-2M-specific T cells

Pre-Treatment % HPV16:E7 12-20-specific T cells

Post-Treatment % HPV16:E7 12-20-specific T cells

Arm A (Every 2 Weeks, gp100:209-217(210M) and HPV 16 E7:12-20)

Arm B (Every 3 Weeks, gp100:209-217(210M) + HPV 16 E7:12-20)

Patients were randomly assigned to two different vaccination schedules: group A received vaccinations every 2 weeks for 6 months (13 total injections), and group B received vaccinations every 3 weeks for 6 months (nine total vaccinations).

T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide

gp100:209-217(210M)and HPV 16 E7:12-20 (Every 2 Weeks)

gp100:209-217(210M) and HPV 16 E7:12-20 (Every 3 Weeks)

Overall Study

Lentigo

Hutchinson's Melanotic Freckle

Lentigo Maligna Melanoma

Acral Lentiginous Melanoma

Nodular Melanoma

examination

mutation carrier screening

study of high risk factors

Contact Person

RATIONALE: A study that evaluates patients' lifestyle, skin, and blood and tissue samples may help doctors understand the risk factors for melanoma relapse.

PURPOSE: This clinical trial is studying the risk factors for melanoma in families with melanoma.

OBJECTIVES:

Primary

* Determine what lifestyle factors and which genes govern relapse from melanoma.

Secondary

* Compare sun exposure and genes that cause melanoma in patients with melanoma vs healthy participants.
* Assess how unusual moles relate to sun exposure and genes that cause melanoma.

OUTLINE: This is a multicenter, cohort study.

Patients and healthy participants complete lifestyle questionnaires by mail and telephone. Some patients\* and healthy participants undergo a skin examination to count moles and classify skin type (e.g., degree of freckling and wrinkling indicative of sun damage).

NOTE: \*Patients diagnosed with primary invasive melanoma after September 2005 do not need to consent to a skin examination.

Patients and healthy participants also undergo blood collection for lymphocyte analysis, DNA extraction, and the measurement of minerals, vitamins, and beta carotene. Tissue samples from original diagnosis are examined by immunohistochemistry for gene expression and mutations, including CDKN2A and CDK4.

Patients and healthy participants are followed annually.

Peer reviewed and funded or endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 3,700 patients and healthy participants will be accrued for this study.

Study of Families With Melanoma

Melanoma Family Case-Control Study Protocol

Hereditary Melanoma

microarray analysis

molecular genetic technique

RATIONALE: Identifying gene mutations and other risk factors in patients with melanoma and in families with a history of hereditary melanoma may help doctors identify persons at risk for melanoma and other types of cancer. It may also help the study of cancer in the future.

PURPOSE: This clinical trial is studying gene mutations in patients with melanoma and in families with a history of hereditary melanoma.

OBJECTIVES:

* Determine the incidence and etiologic significance of variants of known melanoma susceptibility genes (MSGs) in families with multiple cases of melanoma.
* Determine the proportion of multiple-case families that are explained by high-penetrance mutations in known MSGs.
* Determine the proportion of multiple-case families that are explained by these mutations and whether it varies with latitude, as a surrogate for ultraviolet exposure, with number of affected relatives, with average age at onset of melanoma in relatives, with presence of multiple primary melanoma, or with other family-specific variables.
* Determine the penetrance of MSG mutations in these families.
* Determine if the penetrance varies with age, sex, or birth cohort.
* Determine if the penetrance varies with the gene involved or nature of the mutation.
* Assess the penetrance in mutations that also have a deleterious effect on the alternative splice product, p14ARF.
* Determine whether carriers of MSGs have an increased susceptibility to other types of cancer.
* Determine the risk of other types of cancers for mutation carriers.
* Determine environmental exposures, in particular sun exposure, that modify risk of melanoma in MSG mutation carriers.
* Determine the cutaneous phenotypes that correlate with melanoma risk in these families.
* Correlate cutaneous phenotypes with the presence of MSG variants.
* Determine the effect of other covariates, such as sun exposure or the presence of alleles of putative modifying genes (e.g., MC1R or CDKN2A), on phenotype.
* Determine if modifier genes, such as those controlling pigmentation of the skin, and therefore sun susceptibility, modify risk in MSG mutation carriers.
* Identify any histopathological correlates of MSG status in primary tumors arising in melanoma-susceptible individuals in these families.
* Identify any histopathological correlates of primary melanomas in carriers of MSG mutations with other covariates.

OUTLINE: This is a case-control, multicenter study.

Participants complete 2 questionnaires and assist in the creation and expansion of a family pedigree. Blood samples are examined for melanoma susceptibility gene mutations, including CDK4 and CDKN2A.

Participants are also examined for moles and photographed. Physical variables (e.g., skin, eye, and hair pigmentation) and sun damage (solar lentigines and freckling) are also noted.

If available, tissue samples are examined for Clark level, Breslow thickness, and frequency of mitoses. Peri-lesional skin from tumors is examined by p53 staining.

Participants are followed periodically to monitor cancer development.

Peer reviewed and funded or endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 5,000 participants will be accrued for this study.

Identifying Gene Mutations in Patients With Melanoma and in Families With a History of Hereditary Melanoma

Studies of Familial Melanoma

Anti-Infective Agents

Antineoplastic Agents

Interferons

Elieser Gorelik, MD, PhD

RATIONALE: Collecting and storing samples of blood from patients with cancer to study in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer, and may help doctors learn how well patients will respond to treatment.

PURPOSE: This laboratory study is looking at biomarkers to predict the response to interferon therapy in patients with melanoma.

OBJECTIVES:

* Generate a comprehensive multiplexed array of melanoma-associated serological markers and validate it using serum samples from patients with melanoma and healthy control participants.
* Determine changes in the profile of serological markers induced by interferon-alfa 2b (IFN-α2b) therapy.
* Define panels of serological markers with prognostic and predictive power for IFN-α2b therapy responses in patients with melanoma.

OUTLINE: This is a multicenter study.

Serum samples are used for multiplex analyses. Biomarkers to be assessed include cytokines, chemokines, growth factors, angiogenic and antiangiogenic molecules, matrix metalloproteases (MMPs), tissue inhibitors of MMPs (TIMPs), melanoma-associated antigens, basic fibroblast growth factor, insulin-like growth factor I and II, thrombospondin, endostatin, angiostatin, vasostatin, and vascular endothelial growth factor inhibitor.

PROJECTED ACCRUAL: A total of 1,716 samples will be accrued for this study.

Biomarkers to Predict Response to Interferon Therapy in Patients With Melanoma

Multiplex Analysis of Serum Biomarkers for Prediction Interferon Therapy Response in Melanoma Patients

Generation of a comprehensive multiplexed array of melanoma-associated serological markers

Changes in the profile of serological markers induced by interferon-alfa 2b therapy

Panels of serological markers with prognostic and predictive power for interferon-alfa 2b response

ECOG-ACRIN Cancer Research Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Studying Tumor Tissue Samples From Patients With Melanoma Who Have Undergone Sentinel Lymph Node Biopsy	NCT00897481	Melanoma (Skin)	gene expression... mutation analys... diagnostic labo... immunohistochem... sentinel lymph ...	-	National Cancer Institute (NCI)
Studying Tumor Tissue Samples From Patients With Melanoma Who Have Undergone Sentinel Lymph Node Biopsy	NCT00897481	Melanoma (Skin)	gene expression... mutation analys... diagnostic labo... immunohistochem... sentinel lymph ...	-	National Cancer Institute (NCI)
Vaccine Therapy in Treating HLA-A2 Positive Patients With Melanoma	NCT00003895	Recurrent Melan... Stage IA Melano... Stage IB Melano... Stage IIA Melan... Stage IIB Melan... Stage IIC Melan... Stage IIIA Mela... Stage IIIB Mela... Stage IIIC Mela...	HPV 16 E7:12-20 gp100:209-217(2... laboratory biom...	17 Years -	National Cancer Institute (NCI)
Studying Tumor Tissue Samples From Patients With Melanoma Who Have Undergone Sentinel Lymph Node Biopsy	NCT00897481	Melanoma (Skin)	gene expression... mutation analys... diagnostic labo... immunohistochem... sentinel lymph ...	-	National Cancer Institute (NCI)
Study of Families With Melanoma	NCT00445783	Melanoma (Skin)	gene expression... mutation analys... immunohistochem... laboratory biom... examination mutation carrie... study of high r...	18 Years -	National Cancer Institute (NCI)
Vaccine Therapy in Treating HLA-A2 Positive Patients With Melanoma	NCT00003895	Recurrent Melan... Stage IA Melano... Stage IB Melano... Stage IIA Melan... Stage IIB Melan... Stage IIC Melan... Stage IIIA Mela... Stage IIIB Mela... Stage IIIC Mela...	HPV 16 E7:12-20 gp100:209-217(2... laboratory biom...	17 Years -	National Cancer Institute (NCI)
Identifying Gene Mutations in Patients With Melanoma and in Families With a History of Hereditary Melanoma	NCT00450593	Hereditary Mult... Melanoma (Skin)	gene expression... microarray anal... molecular genet... mutation analys... laboratory biom... mutation carrie... study of high r...	-	National Cancer Institute (NCI)
Biomarkers to Predict Response to Interferon Therapy in Patients With Melanoma	NCT00897546	Melanoma (Skin)	laboratory biom...	18 Years - 120 Years	Eastern Cooperative Oncology Group

Spots Global Cancer Trial Database for stage ia melanoma