Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Infections

Rare Diseases

Recurrence

Melanoma

Lentigo

Adenoviridae Infections

Hutchinson's Melanotic Freckle

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

Lentigo Maligna Melanoma

Acral Lentiginous Melanoma

Superficial Spreading Melanoma

Nodular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

All Drugs and Chemicals

Ganciclovir

Ganciclovir triphosphate

Antiviral Agents

Enzyme Inhibitors

adenovirus RSV-TK

ganciclovir

John C. Morris, MD

RATIONALE: Inserting a modified herpesvirus gene into a person's melanoma cells may make the cancer more sensitive to the antiviral agent ganciclovir.

PURPOSE: Phase I trial to study the effectiveness of gene therapy in treating patients who have stage IV melanoma.

OBJECTIVES: I. Determine the maximum tolerated dose of ganciclovir administered IV every 12 hours for 7 days in combination with adenovirus RSV-TK administered by direct intralesional injection in patients with cutaneous or subcutaneous metastatic malignant melanoma. II. Determine the dose limiting toxicities of this regimen in this patient population. III. Evaluate the response (both local and at distant metastatic sites), duration of response, response by ganciclovir dose, and any impact local treatment with adenovirus RSV-TK and ganciclovir "suicide" gene therapy may have on overall survival in these patients.

OUTLINE: This is a dose escalation study of ganciclovir. Patients are stratified according to response of the index lesion and other metastatic disease sites. Patients receive an intratumoral injection of adenovirus RSV-TK on day 1. Ganciclovir IV is administered every 12 hours on days 3-10 for a total of 14 doses. Patients sustaining a partial response (PR) or complete response (CR) may be retreated 2 weeks after documented PR or CR. Cohorts of 3-6 patients receive escalating doses of ganciclovir until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Patients are followed at 3 weeks, 4 weeks, 60 days, then every 2 months for 6 months, and then every 3 months for 1.5 years.

PROJECTED ACCRUAL: A maximum of 27 patients will be accrued for this study.

Gene Therapy and Ganciclovir in Treating Patients With Stage IV Melanoma

A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination With Escalating Doses of Ganciclovir in Patients With Cutaneous Metastatic Malignant Melanoma

National Cancer Institute (NCI)

National Human Genome Research Institute (NHGRI)

Antineoplastic Agents

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Cohort A participants received 50 mg sunitinib orally daily for 4 weeks followed by a two-week break from treatment. These 6-week cycles would be repeated until progression or unacceptable toxicity up to 1 year.

Cohort B participants received 37.5 mg sunitinib daily on a continuous basis until progression or unacceptable toxicity up to 1 year.

F. Stephen Hodi, MD

The purpose of this study is to evaluate how effective Sunitinib works in treating acral lentiginous and mucosal melanoma which has spread beyond the local region. Suninitib is a protein-tyrosine kinase inhibitor and acts as a c-kit inhibitor drug. It is believed to work by blocking signals on certain cancer cells which allow the malignant cells to multiply and spread due to a change in the genetic make up of the cancer cell.

OBJECTIVES:

Primary

* To determine the proportion of participants with metastatic mucosal or acral/lentiginous melanoma who are alive and without disease progression at two months after beginning treatment with sunitinib.
* To determine the best overall response rate.

Secondary

* To determine the time to progression and overall survival.
* To correlate c-kit mutational status with response to therapy.
* To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
* To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.

SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

A Phase II Study of SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

2-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 2 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

The best overall response rate was defined as achieving partial response (PR) or complete response (CR) on treatment based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Overall survival (OS) is defined as the time from study entry to death or date last known alive.

Time to progression based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Beth Israel Deaconess Medical Center

Massachusetts General Hospital

Pfizer

Dana-Farber Cancer Institute

Melanoma Disease Center Director

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.

Cohort A participants received 50 mg sunitinib orally daily for 4 weeks followed by a two-week break from treatment. These 6-week cycles would be repeated until progression or unacceptable toxicity up to 1 year.

Cohort A-Sunitinib Intermittent Dosing

Cohort B participants received 37.5 mg sunitinib daily on a continuous basis until progression or unacceptable toxicity up to 1 year.

Cohort B-Sunitinib Continuous Dosing

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The analysis dataset is comprised of treated patients.

2-month Progression-free Survival Rate

Best Overall Response Rate

Overall Survival

The analysis dataset is comprised of treated patients. The majority of patients were off-treatment due to disease progression and thus the relevant observation time frame for this outcome is time on treatment.

Time to Progression

Overall Study

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Tyrosine

Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.

imatinib mesylate

laboratory biomarker analysis

Richard Carvajal

This phase II trial is studying how well imatinib mesylate works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. Determine the overall objective response rate (complete response and partial response) in patients with inoperable stage III or IV melanoma harboring somatic alterations in c-KIT treated with imatinib mesylate.

SECONDARY OBJECTIVES:

I. Determine the time to progression in patients treated with this drug. II. Determine if c-KIT mutational status by DNA sequencing, DNA copy number status by fluorescent in situ hybridization (FISH) or comparative genomic hybridization, and/or protein expression by immunohistochemistry (IHC) can best predict clinical benefit from imatinib mesylate.

TERTIARY OBJECTIVES:

I. To evaluate tumors resistant to small molecule inhibitors of Kit for the development of secondary Kit mutations or for changes in Kit copy number.

II. To evaluate for changes in Ki-67, phospho-Akt, phospho-MEK, phospho-S6, phospho STAT3, cleaved caspase 3, IGF-1R, and Kit expression in paired tumor samples obtained from patients treated with a small molecule inhibitor of Kit.

III. To analyze baseline and post-resistance blood samples for soluble cKIT levels, soluble VEGFR1, soluble VEGFR2, VEGF, PlGF, FGF, and melanoma inhibitory activity (MIA) levels, and circulating tumor cells.

IV. To analyze concomitant samples of blood and tumor for imatinib levels in patients treated with imatinib.

OUTLINE: This is a multi-center study. Patients are stratified according to true amplification of c-KIT by FISH vs mutations by DNA sequencing.

Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples or unstained tissue slides/paraffin blocks may be collected. c-KIT is evaluated by IHC and comparative genomic hybridization.

After completion of study treatment, patients are followed up periodically.

Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

A Phase II Study of Imatinib Mesylate (STI571;NSC#716051:IND 61135) in Patients With Inoperable AJCC Stage III or IV Melanoma Harboring Somatic Alterations of C-KIT

Response will be evaluated in this study using the new international criteria proposed by the RECIST Committee. A Simon two-stage minimax design will be employed.

Progression will be evaluated in this study using the new international criteria proposed by the RECIST Committee. Time to progression will be estimated using the Kaplan-Meier method.

Patients receive oral imatinib mesylate 400 mg twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.

imatinib mesylate: Given orally

laboratory biomarker analysis: Correlative studies

Treatment (Enzyme Inhibitor Therapy)

Age, Categorical

Dr. Richard Carvajal

Complete Response

Partial Response

Stable Disease

Progression of Disease

Objective Response Rate

gene expression analysis

mutation analysis

immunohistochemistry staining method

examination

mutation carrier screening

study of high risk factors

Contact Person

Julia Newton Bishop, MD

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

Leeds Cancer Centre at St. James's University Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gene Therapy and Ganciclovir in Treating Patients With Stage IV Melanoma	NCT00005057	Melanoma (Skin)	adenovirus RSV-... ganciclovir	18 Years -	National Cancer Institute (NCI)
SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma	NCT00577382	Mucosal Lentigi... Acral Lentigino...	Sunitinib	18 Years -	Dana-Farber Cancer Institute
Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery	NCT00470470	Acral Lentigino... Recurrent Melan... Stage IIIA Mela... Stage IIIB Mela... Stage IIIC Mela... Stage IV Melano...	imatinib mesyla... laboratory biom...	18 Years -	National Cancer Institute (NCI)
Gene Therapy and Ganciclovir in Treating Patients With Stage IV Melanoma	NCT00005057	Melanoma (Skin)	adenovirus RSV-... ganciclovir	18 Years -	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)
Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery	NCT00470470	Acral Lentigino... Recurrent Melan... Stage IIIA Mela... Stage IIIB Mela... Stage IIIC Mela... Stage IV Melano...	imatinib mesyla... laboratory biom...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for acral lentiginous malignant melanoma