Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Cholangiocarcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Percutaneous hepatic perfusion with melphalan hydrochloride for injection using the Hepatic Delivery System on patients with Hepatocellular carcinoma (HCC).

Melphalan hydrochloride is administered at a dose of 3mg/kg ideal body weight once every 6 weeks for a maximum of 2 cycles of treatment.

Percutaneous hepatic perfusion with melphalan hydrochloride for injection using the Hepatic Delivery System on patients with Intrahepatic cholangiocarcinoma (ICC).

Melphalan hydrochloride is administered at a dose of 3mg/kg ideal body weight once every 6 weeks for a maximum of 2 cycles of treatment.

Delcath Hepatic Delivery System

Johnny John, MD

This is a two arm, open label, multi-center, Phase 2 study to evaluate the efficacy and safety of Melphalan/HDS in patients with unresectable Hepatocellular Carcinoma (HCC) or Intra Hepatic Cholangiocarcinoma (ICC) confined to the liver.

This is a two arm, open label, multi-center, Phase 2 study to evaluate the efficacy and safety of Melphalan/HDS in patients with unresectable HCC or ICC confined to the liver.

Eligible patients will receive up to 2 Melphalan/HDS treatments. Each treatment cycle consists of 6 weeks with an acceptable delay for another 2 weeks before next planned treatment. Tumor response will be assessed at the end of cycle 2.

The Melphalan/HDS treatment will be terminated in patients with progressive disease (PD) after the 1st treatment and based on safety in patients with \> 8 weeks delay of recovery from toxicity.

Melphalan for Use With the Hepatic Delivery System Treatment in Patients With Unresectable Hepatocellular Carcinoma or Intra Hepatic Cholangiocarcinoma

An International Multi-center Phase 2 Study to Evaluate the Efficacy and Safety of Melphalan Hydrochloride for Injection for Use With the Hepatic Delivery System Treatment in Patients With Unresectable Hepatocellular Carcinoma or Intra Hepatic Cholangiocarcinoma

Delcath Systems Inc.

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Eye Diseases

Neoplasm Metastasis

Melanoma

Uveal Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Eye Neoplasms

Uveal Diseases

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Immunomodulating Agents

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

The effect of ipilimumab and nivolumab has previously been tested in metastatic uveal melanoma. In this study the combination with percutaneous hepatic perfusion will be performed in order to evaluate the effect.

Ipilimumab and nivolumab

Melphalan chemosaturation via percutaneous hepatic perfusion

Ellen W. Kapiteijn, MD, PhD

Mark C. Burgmans, MD, PhD

Ellen Kapiteijn, MD, PhD

Frank Speetjens, MD, PhD

Thaïs Tong, MD

Melanoma of the eye (ocular/uveal melanoma) is an uncommon type of cancer that is associated with a high mortality. It usually disseminates rapidly throughout the body, most commonly to the liver and lungs. In this study a combination therapy with immunotherapy (ipilimumab with nivolumab) and chemotherapy (melphalan) will be assessed for the treatment of disseminated uveal melanoma. Melphalan will be administered selectively to the liver via percutaneous hepatic perfusion, limiting the systemic effect of chemotherapy. With this treatment combination we aim to find a treatment for disseminated uveal melanoma, both in the liver as in the other organs.

Uveal melanoma (UM) is an uncommon malignancy (0.6-0.7 cases/100.000/year) that, in the case of metastatic stage, has a poor prognosis for response to treatment and survival. It is remarkable for its purely hematogenous pattern of dissemination, most commonly to the liver (60%) and lungs (25%). Current approaches using percutaneous hepatic perfusion (PHP) with melphalan resulted in response rates of up to 40% in the liver (1, 2) (for results of our own phase II study see paragraph 6.3.2). However, a main part of the patients developed extrahepatic disease in the follow-up, whereas the liver metastases were mainly stable.

Checkpoint inhibitors have been shown to improve overall survival in metastasized cutaneous melanoma in phase III studies (3-6), but seem to have limited activity as monotherapies in metastasized uveal melanoma (7-9). The combination of ipilimumab and nivolumab has achieved 2 out of 6 patients PR in a retrospective analysis (10). Interestingly, both patients had a liver-directed therapy (SIRT and chemoembolization) before the immunotherapy.

Combination of radio-frequency ablation (RFA) and anti-CTLA-4 enhanced antigen-loading of dendritic cells, and induced long-lasting anti-tumor immune responses in a murine melanoma model without induction of any severe side effects (11, 12). A phase Ib/II trial by Blank et al. (13) showed unconfirmed responses in some patients when RFA was combined with ipilimumab in uveal melanoma, but long-term disease stabilization was not achieved. Most of the responses were seen in extrahepatic metastases. Combining percutaneous hepatic perfusion (PHP) with checkpoint inhibitors could together lead to control of hepatic and extrahepatic disease. Therefore, we propose the current trial: Phase1b/2 Study Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced Uveal Melanoma (CHOPIN).

In the phase 1b part, safety and feasibility of combining percutaneous hepatic perfusion with 4 courses of ipilimumab and nivolumab will be investigated. In the randomized phase 2 part, efficacy as measured by progression-free survival at one year comparing PHP only versus PHP plus ipilimumab/nivolumab will be evaluated.

Open label, single center, phase Ib/randomized phase II trial, evaluating the safety and efficacy (as measured by RECIST 1.1) of the combination of PHP and ipilimumab/nivolumab in patients with unresectable hepatic and extrahepatic metastases of uveal melanoma.

PHP and Immunotherapy in Metastasized UM

Phase1b/2 Study Combining Hepatic Percutaneous Perfusion With Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma

Dose limiting toxicities, maximum tolerated dose and recommended phase dose of the combination ipilimumab/nivolumab and PHP in patients with unresectable, histologically confirmed hepatic metastasis of uveal melanoma in phase Ib part.

Description of PFS according to RECIST 1.1 at one year in the PHP group versus PHP + ipilimumab/nivolumab group in the phase II part.

Description of response rate and overall survival, overall clinical response, and duration of response

Leiden University Medical Center

MD, PhD

Melanoma, Cutaneous Malignant

Ocular Melanoma

Hematinics

Liver Extracts

Percutaneous Hepatic Perfusion

Charles W Nutting, DO

Jonathan Zager, MD

Mark Faries, MD

James F Pingpank, MD

Eric D Whitman, MD

H. Richard Alexander, MD

The safety and efficacy of CS-PHP-melphalan has been evaluated in a phase 3 trial conducted in the same patient population as well as using the same melphalan dosing as proposed in this study. This expanded access protocol will provide an experimental alternative treatment option for both physicians and patients until the Delcath CS-PHP System receives marketing approval.

Expanded Access Study of Melphalan With Delcath CS-PHP System in Patients With Ocular/Cutaneous Melanoma Mets to Liver

An Open Label, Expanded Access Study of Melphalan Chemosaturation With the Delcath System in Patients With Ocular and Cutaneous Melanoma Metastatic to the Liver

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Melphalan for Use With the Hepatic Delivery System Treatment in Patients With Unresectable Hepatocellular Carcinoma or Intra Hepatic Cholangiocarcinoma	NCT02415036	Hepatocellular ... Intrahepatic Ch...	Delcath Hepatic... Melphalan	18 Years -	Delcath Systems Inc.
PHP and Immunotherapy in Metastasized UM	NCT04283890	Uveal Melanoma,...	Ipilimumab and ... Melphalan chemo...	18 Years - 75 Years	Leiden University Medical Center
Melphalan for Use With the Hepatic Delivery System Treatment in Patients With Unresectable Hepatocellular Carcinoma or Intra Hepatic Cholangiocarcinoma	NCT02415036	Hepatocellular ... Intrahepatic Ch...	Delcath Hepatic... Melphalan	18 Years -	Delcath Systems Inc.
PHP and Immunotherapy in Metastasized UM	NCT04283890	Uveal Melanoma,...	Ipilimumab and ... Melphalan chemo...	18 Years - 75 Years	Leiden University Medical Center
Expanded Access Study of Melphalan With Delcath CS-PHP System in Patients With Ocular/Cutaneous Melanoma Mets to Liver	NCT01728051	Metastatic Live... Ocular Melanoma Cutaneous Melan...	Melphalan Percutaneous He...	18 Years -	Delcath Systems Inc.
Expanded Access Study of Melphalan With Delcath CS-PHP System in Patients With Ocular/Cutaneous Melanoma Mets to Liver	NCT01728051	Metastatic Live... Ocular Melanoma Cutaneous Melan...	Melphalan Percutaneous He...	18 Years -	Delcath Systems Inc.

Spots Global Cancer Trial Database for percutaneous hepatic perfusion