Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Eye Diseases

Rare Diseases

Melanoma

Neoplasm Metastasis

Uveal Neoplasms

Iris Neoplasms

Choroid Neoplasms

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

Eye Neoplasms

Uveal Diseases

Choroid Diseases

Iris Diseases

Ocular Melanoma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Fine needle aspiration biopsy

J. William Harbour, MD

Up to half of patients with ocular melanoma (also called iris, choroidal or uveal melanoma) develop metastasis. We have found that certain molecular features of the eye tumor can be detected by gene expression profiling and accurately predict which patients will develop metastasis. This molecular test could eventually allow high risk patients to receive preventative therapy to delay or prevent the development of metastasis. The goal of this study is to prospectively validate the predictive accuracy of the gene expression-based molecular test and compare it to monosomy 3, the most common but potentially less accurate molecular marker for metastasis in ocular melanoma.

We have discovered a gene expression profile derived from primary uveal melanomas that accurately predicts which patients will develop metastasis. Tumors with a class 1 gene expression signature have a very low risk, and those with a class 2 signature have a high risk of metastasis. The molecular test was initially performed on tissue obtained from enucleated eyes using commercial microarray platforms. We are now able to perform the molecular test on fine needle biopsy specimens, and we have developed a customized test that has greater dynamic range and sensitivity than commercial microarray platforms. The goal of this study is to validate the prognostic accuracy of the customized platform by performing the molecular test on primary uveal melanomas obtained from enucleation, local tumor resection or fine needle biopsy. Each sample will be diagnosed as either class 1, class 2 or indeterminate. Outcomes will be collected and the ability of the molecular diagnosis to predict metastasis will be evaluated at regular intervals.

Validation of a Molecular Prognostic Test for Eye Melanoma

Validation of a Molecular Test for Predicting Metastasis in Patients With Uveal Melanoma

Washington University School of Medicine

Recurrence

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Temozolomide

Interferons

Peginterferon alfa-2b

Interferon-alpha

Interferon alpha-2

Antiviral Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunologic Factors

pegylated interferon alfa

temozolomide

Wen-Jen Hwu, MD, PhD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of cancer cells. Combining chemotherapy with interferon alfa may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining temozolomide and interferon alfa in treating patients who have stage III or stage IV melanoma.

OBJECTIVES:

* Determine the response rate in patients with advanced melanoma treated with temozolomide and pegylated interferon alfa.
* Determine the toxicity profile of this regimen in these patients.
* Determine the duration of disease response and overall survival of patients treated with this regimen.

OUTLINE: Patients are stratified according to CNS metastases (yes vs no).

Patients receive oral temozolomide once daily on weeks 1-6 and pegylated interferon alfa subcutaneously once weekly on weeks 1-8. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 23-61 patients (12-35 without CNS metastases and 11-26 with CNS metastases) will be accrued for this study within 18 months.

Temozolomide and Interferon Alfa in Treating Patients With Stage III or Stage IV Melanoma

A Phase II Study of Temozolomide (Temodar) and Peglated Interferon Alfa-2B (PEGIntron) in the Treatment of Advanced Melanoma

National Cancer Institute (NCI)

Memorial Sloan Kettering Cancer Center

Digestive System Diseases

Gland and Hormone Related Diseases

Syndrome

Esophageal Neoplasms

Pheochromocytoma

Carcinoma

Cholangiocarcinoma

Adenocarcinoma

Pancreatic Neoplasms

Thyroid Diseases

Stomach Neoplasms

Liver Neoplasms

Carcinoid Tumor

Carcinoma, Medullary

Carcinoma, Islet Cell

Insulinoma

Glucagonoma

Somatostatinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Esophageal Cancer

Pancreatic Cancer

Bile Duct Cancer

Stomach Cancer

Primary Liver Cancer

Gallbladder Cancer

Small Intestinal Adenocarcinoma

Thyroid Cancer, Medullary

Small Intestine Cancer

Conjunctival Melanoma

WDHA Syndrome

Hematinics

Gastrointestinal Agents

Herbal and Botanical

Melphalan

Liver Extracts

Pancrelipase

Pancreatin

Pancreatic Polypeptide

Immunosuppressive Agents

Cola

isolated perfusion

melphalan

Marybeth Hughes, MD

RATIONALE: Hepatic arterial infusion uses a catheter to deliver anticancer substances directly into the liver. Drugs used in chemotherapy, such as melphalan, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs in different ways may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving an hepatic arterial infusion of melphalan together with hepatic perfusion works in treating patients with unresectable liver cancer.

OBJECTIVES:

Primary

* Determine the response rate and duration of response in patients with unresectable primary or metastatic liver cancer treated with intrahepatic arterial infusion of melphalan with venous filtration via peripheral hepatic perfusion.

Secondary

* Determine the patterns of recurrence in patients treated with this regimen.
* Determine progression-free and overall survival of patients treated with this regimen.
* Evaluate the safety and tolerability of this regimen in these patients.
* Assess the filter characteristics including melphalan pharmacokinetics and filtration of cytokines and clotting factors during and after treatment.

OUTLINE: Patients are stratified according to primary tumor histology (neuroendocrine tumor vs primary hepatic malignancy vs adenocarcinoma of gastrointestinal or other origin).

Patients undergo peripheral isolated hepatic perfusion in which a catheter is placed via the groin into the hepatic artery and another into the hepatic vein. Patients then receive melphalan as an intrahepatic arterial infusion over 15-30 minutes. Treatment repeats approximately every 3-8 weeks for up to 6 total infusions in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 4 months for 1 year, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study within 4-5 years.

Hepatic Arterial Infusion of Melphalan With Hepatic Perfusion in Treating Patients With Unresectable Liver Cancer

A Phase II Study Of Hepatic Arterial Infusion Of Melphalan With Venous Filtration Via Peripheral Hepatic Perfusion (PHP) For Unresectable Primary And Metastatic Cancers Of The Liver

Delcath Systems Inc.

Melanoma, Cutaneous Malignant

Acral Lentiginous Melanoma

Antirheumatic Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Interleukin-2

Mesna

Analgesics, Non-Narcotic

TBio-4101 is a tumor-infiltrating lymphocyte (TIL) product: participants tumor tissue is surgically removed and immune T-cells are taken out of the tumor and multiplied, or grown, in the laboratory. TIL product infused intravenously over 20 to 30 minutes within 2 to 4 days after the last dose of fludarabine

Participants will also receive:

* Cyclophosphamide dose 60 mg/kg/day for 2 days administered IV in 250 mL dextrose 5% in water infused simultaneously with Mesna 15 mg/kg/day delivered over 1 hour per day for 2 days. Fludarabine 25 mg/m2/day is delivered by intravenous piggyback daily over 15-30 minutes for 5 days.
* Interleukin-2 (IL-2)- will be given to participants through IV after they receive the infusion of the TIL. IL-2 is administered at a dose of 600,000 IU/kg (based on actual body weight) IV every 8-12 hours beginning within 24 hours of TIL infusion for a maximum of 6 doses.

TBio-4101 is a tumor-infiltrating lymphocyte (TIL) product that involves the use of special immune cells called T-cells. A T-cell is a type of lymphocyte, or white blood cell.

TBio-4101

Participants will receive Cyclophosphamide 60 mg/kg/day intravenously (IV) in 250 mL over approximately 1 hour per day for 2 days.

Participants will receive an intravenously (IV) infusion of Fludarabine 25 mg/m2 for approximately 15 to 30 minutes for 5 days, prior to T-Cell infusion

Participants will receive Interleukin-2 (IL-2) 600 000 IU/kg intravenously every 8 to 12 hours beginning within 24 hours after T-cell infusion.

Yvonne Nguyen

Amod Sarnaik, MD

Veron Sondak, MD

The purpose of this first in human study is to evaluate the feasibility, safety, and efficacy of administering TBio-4101 (tumor infiltrating lymphocytes \[TIL\]) after receiving a lymphodepleting chemotherapy regimen and before receiving interleukin-2 (IL-2) in participants with unresectable or metastatic melanoma.

Proof of Concept of TBio-4101, Lymphodepleting Chemo, IL-2 for Relapsed/Refractory Melanoma

A Proof of Concept Study of TBio-4101 (an Autologous Selected and Expanded Tumor Infiltrating Lymphocyte [TIL] Therapy) Using Short-Term Cultured, Selected Autologous TIL Following a Lymphodepleting Chemotherapy Regimen and Followed by IL-2 for Patients With Relapsed or Refractory Melanoma (Phase 1)

Percentage of participants who undergo tumor resection that successfully receive TBio-4101

ORR will be calculated using irRECIST and RECIST v1.1

OS is defined as the time from enrollment to death

PFS is defined as the time from study enrollment until disease progression or death.

DRR is defined as a continuous response, beginning within 12 months of treatment and lasting \> 6 months

Turnstone Biologics, Corp.

H. Lee Moffitt Cancer Center and Research Institute

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Validation of a Molecular Prognostic Test for Eye Melanoma	NCT00406120	Uveal Neoplasms Choroid Neoplas... Iris Neoplasms	Fine needle asp...	-	Washington University School of Medicine
Temozolomide and Interferon Alfa in Treating Patients With Stage III or Stage IV Melanoma	NCT00027742	Intraocular Mel... Melanoma (Skin)	pegylated inter... temozolomide	18 Years -	Memorial Sloan Kettering Cancer Center
Hepatic Arterial Infusion of Melphalan With Hepatic Perfusion in Treating Patients With Unresectable Liver Cancer	NCT00096083	Cancer	isolated perfus... melphalan	16 Years -	Delcath Systems Inc.
Temozolomide and Interferon Alfa in Treating Patients With Stage III or Stage IV Melanoma	NCT00027742	Intraocular Mel... Melanoma (Skin)	pegylated inter... temozolomide	18 Years -	Memorial Sloan Kettering Cancer Center
Validation of a Molecular Prognostic Test for Eye Melanoma	NCT00406120	Uveal Neoplasms Choroid Neoplas... Iris Neoplasms	Fine needle asp...	-	Washington University School of Medicine
Proof of Concept of TBio-4101, Lymphodepleting Chemo, IL-2 for Relapsed/Refractory Melanoma	NCT05628883	Metastatic Mela... Unresectable Me... Acral Melanoma Mucosal Melanom... Cutaneous Melan... Ocular Melanoma Uveal Melanoma Iris Melanoma Conjunctival Me... Non-Cutaneous M...	TBio-4101 Cyclophosphamid... Fludarabine Interleukin-2	18 Years - 75 Years	H. Lee Moffitt Cancer Center and Research Institute

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