An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular Melanoma

NCT05022901 | Unknown Phase 3 FDA Drug

• 1 other identifier: PHP-OCM-501
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

Patients in the study will be treated with Melphalan/HDS and will receive up to 6 total treatments. This study will evaluate the safety and effects of the treatment.

Conditions

Metastatic Ocular Melanoma; Metastatic Uveal Melanoma

Keywords

percutaneous hepatic perfusion; PHP; uveal melanoma; HEPZATO

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  The number and type of adverse events will be assessed per CTCAE version 5.0.

  From eligibility until death due to any cause, for up to 104 weeks

Secondary Outcomes (4)

• Efficacy (ORR)

  Every 12 (+/-2) weeks until progression, for up to 104 weeks

• Efficacy (OS)

  From eligibility until death due to any cause, for up to 104 weeks

• Efficacy (PFS)

  Every 12 (+/-2) weeks until progression, for up to 104 weeks

• Quality of Life (FHSI-8)

  Every 6-8 weeks until the end of treatment, for up to 52 weeks

Study Arms (1)

Melphalan/HDS

EXPERIMENTAL

Eligible patients will be treated with Melphalan/HDS 3.0 mg/kg Ideal Body Weight (IBW). Melphalan/HDS treatment will be administered every 6 weeks for a total of 6 cycles with an acceptable delay of another 2 weeks before the next planned treatment to allow for recovery of melphalan-related toxicity, if needed.

Combination Product: Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS)

Interventions

Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS) COMBINATION_PRODUCT

Melphalan administered directly to the liver via the Hepatic Delivery System (HDS) infused over a 30 minute period, followed by a 30 minute washout period

Also known as: percutaneous hepatic perfusion, PHP, HEPZATO

Melphalan/HDS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age.
• Patients must weigh ≥ 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic Delivery System).
• % or less histologically or cytologically-proven ocular melanoma metastases in the parenchyma of the liver.
• Disease in the liver must be measurable by computed tomography (CT) and/or magnetic resonance imaging (MRI).
• Evidence of limited extrahepatic disease on preoperative radiological studies is acceptable if the life-threatening component of disease is in the liver. Limited extrahepatic disease is defined in this protocol as follows: metastasis in bone, subcutaneous, lung or lymph nodes that is amenable to resection or radiation and has a defined treatment plan. Patients with extra-hepatic tumor burden which does not have a defined treatment plan (i.e. monitor or is unable to be resected or radiated) must not be included in the trial.
• Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within 28 days prior to eligibility. An MRI of the liver is required at screening to validate that CT accurately reflects the extent of disease in the liver. For patients with MRI intolerance, a 3-phase liver CT is to be done in place of liver MRI.
• Patients must not have had chemotherapy, radiotherapy, chemoembolization, radioembolization, or immunoembolization for their malignancy within 30 days prior to treatment and must have recovered from all side effects of therapeutic and diagnostic interventions except those listed in Appendix B of the study protocol.
• Patients receiving anti programmed cell death protein 1 (PD-1) immunotherapy such as pembrolizumab or nivolumab, or human cytotoxic T-lymphocyte antigen 4 blocking antibody such as ipilimumab must have completed treatment 8 weeks prior to study eligibility.
• Patients must have an ECOG PS of 0-1 at screening.
• Patients must have adequate hepatic function as evidenced by total serum bilirubin ≤1.5 x the upper limit of normal (ULN) and a prothrombin time (PT) within 2 seconds of the upper normal limit. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) must be ≤ 2.5 x ULN.
• Patients must have a platelet count \> 100,000/µL, hemoglobin ≥ 10.0 gm/dL, white blood cell count (WBC) \> 2,000/uL, absolute neutrophil count ≥ 1.5 x 109/L, and a serum creatinine ≤ 1.5 mg/dL unless the measured creatinine clearance is \> 40 mL/min/1.73 m2.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (β-human chorionic gonadotropin) within 7 days prior to eligibility.
• Provided signed informed consent.

You may not qualify if:

• Patients with Child-Pugh Class B or C cirrhosis or with evidence of portal hypertension by history, endoscopy, or radiologic studies.
• Those with New York Heart Association functional classification II, III or IV active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
• History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
• Women of childbearing potential (WOCBP) i.e. fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months) unable to undergo hormonal suppression to avoid menstruation during treatment.
• WOCBP and fertile males (not permanently sterile by bilateral orchiectomy) unwilling or unable to use highly effective contraception method from consent to at least 6 months after the last administration of study treatment (e.g. combined hormonal contraception; progestogen-only hormonal contraception; Intrauterine device, intrauterine hormone-releasing system; bilateral tubal occlusion, vasectomized partner or sexual abstinence).
• Females that are pregnant or are breastfeeding.
• Patients taking immunosuppressive drugs; however, oral corticosteroids ≤ 10 mg/ day are allowed.
• Patients who are unable to be temporarily removed from chronic anti-coagulation therapy.
• Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until completion of appropriate therapy.
• Patients with severe allergic reaction to iodine contrast, which cannot be controlled by premedication with antihistamines and steroids.
• Patients with a history of or known hypersensitivity to melphalan or the components of the Melphalan/HDS system.
• Patients with latex allergy.
• Patients with a history of hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
• Patients with a history of bleeding disorders or evidence of intracranial abnormalities which would put them at risk for bleeding with anti-coagulation (e.g., strokes, active metastases).
• Patients with a history of gastrinoma, NOTE: For patients with a history of liver surgery or major vasculature surgery, a CT angiogram or MR angiogram is required during screening to assure the patient does not have hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting.

Sponsors & Collaborators

• Delcath Systems Inc.: lead

Study Sites (5)

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

Moffitt Cancer Center

Tampa, Florida, 12902, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Melphalan

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 26, 2021
• Study Start: June 10, 2022
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: December 21, 2023

Record last verified: 2023-12

Locations

US (5)