Percutaneous Hepatic Perfusion in Patients With Hepatic-dominant Ocular Melanoma

NCT02678572 | Completed Phase 3 DMC

• 1 other identifier: PHP-OCM-301A
• Study Type: interventional
• Target: 102
• Locations: 9 countries
• Sites: 24

Brief Summary

This study will evaluate patients who have melanoma that has spread from the eye to the liver: Patients in the study will be treated with Melphalan/HDS up to 6 total treatment, and will be followed until death. This study will evaluate the safety and effects of the treatment on how long patients live and how long it takes for the cancer to advance or respond to the treatment.

Conditions

Melanoma, Ocular

Keywords

uveal liver PHP hepatic perfusion chemosaturation Delcath

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) as determined by Independent Central Review Committee

  ORR (complete or partial response)

  Patients will be assessed for ORR from baseline through completion of treatment. [assessed up to 36 months]

Secondary Outcomes (4)

• Duration of Response (DOR) as determined by Independent Central Review Committee

  From time of 1st treatment until there is evidence of disease progression [assessed up to 36 months]

• Disease Control Rate (DCR) determined by Independent Central Review Committee

  ORR will be assessed every 10-14 weeks from the start of 1st treatment and continues until the earlier of either when there is evidence of disease progression or 1 year from 1st treatment.

• Overall Survival

  From the start of the study to the date the patient was last known alive. [assessed up to 36 months]

• Progression-Free Survival

  From start of study until disease progression. [assessed up to 36 months]

Other Outcomes (10)

• Time to Objective Response (TOR)

  From study start through study completion. [Assessed up to 36 months]

• The summary of ORR, DOR, DCR, PFS and TOR as determined from the Investigator-assessed objective response will follow the same approach as those determined by the IRC

  Assessed from the start of 1st treatment and continues until there is evidence of disease progression or 1 year from 1st treatment.

• Hepatic Progression Free Survival (hPFS)

  Assessed from the start of study through evidence of hepatic disease progression [Assessed up to 36 months]

Study Arms (1)

Melphalan/HDS

EXPERIMENTAL

3 mg/kg ideal body weight of melphalan for infusion administered directly to the liver via percutaneous hepatic perfusion (PHP) over 30 minutes followed by a 30 minute washout. Treatment cycles are to be repeated every 6-8 weeks until disease progression.

Combination Product: Melphalan/HDS

Interventions

Melphalan/HDS COMBINATION_PRODUCT

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

Also known as: Alkeran

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 randomization. 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 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 should wait 8 weeks before Melphalan/HDS treatment.
• Patients must have an ECOG PS of 0-1 at screening and on the day prior to treatment.
• 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 (ANC) ≥ 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 randomization.
• 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 orchidectomy) unwilling or unable to use highly effective contraception method for 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 breastfeeding patients
• 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 (because a hepatic angiogram is needed for the Delcath system procedure).
• 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, hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting.

Sponsors & Collaborators

• Delcath Systems Inc.: lead
• IQVIA Biotech: collaborator

Study Sites (24)

University of Arizona

Tucson, Arizona, 85719, United States

Location

Stanford University

Palo Alto, California, 19380, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University James Cancer Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

Universitätsklinikum Graz

Graz, 8036, Austria

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

Centre Léon Bérard

Lyon, Rhône, 69373, France

Location

Charité Unversitätsmedizin Berlin Comprehensive Cancer Center

Berlin, 10117, Germany

Location

Universitätsklinikum Giessen und Marburg

Marburg, 35043, Germany

Location

Universitätshautklinik Münster

Münster, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Clínic Barcelona

Barcelona, 08036, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

University Hospital Southampton NHS Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Aintree University Hospital

Liverpool, L9 7AL, United Kingdom

Location

Related Publications (1)

• Zager JS, Orloff M, Ferrucci PF, Choi J, Eschelman DJ, Glazer ES, Ejaz A, Howard JH, Richtig E, Ochsenreither S, Reddy SA, Lowe MC, Beasley GM, Gesierich A, Bender A, Gschnell M, Dummer R, Rivoire M, Arance A, Fenwick SW, Sacco JJ, Haferkamp S, Weishaupt C, John J, Wheater M, Ottensmeier CH. Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study. Ann Surg Oncol. 2024 Aug;31(8):5340-5351. doi: 10.1245/s10434-024-15293-x. Epub 2024 May 4.

  PMID: 38704501 DERIVED

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 Officials

• Jonathan Zager, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a multi-center, single-arm, open-label study to evaluate the efficacy and safety of Melphalan/HDS in patients with hepatic dominant metastatic ocular melanoma. The study will be conducted at approximately 40 centers in the United States and Europe.

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: February 10, 2016
• Study Start: February 1, 2016
• Primary Completion: May 18, 2023
• Study Completion: August 15, 2023
• Last Updated: December 21, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); ES (2); BE (1); IT (1); FR (1); US (10); DE (5); CH (1); GB (2)