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

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.

Study Overview

• Status: No longer available
• Conditions: Ocular Melanoma; Cutaneous Melanoma; Metastatic Liver Cancer
• Intervention / Treatment: Drug: Melphalan; Device: Percutaneous Hepatic Perfusion

• Study Type: Expanded Access

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute at Saint John's Health Center
  • Colorado
    • Englewood, Colorado, United States, 80112
      • Sky Ridge Medical Center
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07962-1956
      • Carol G. Simon Cancer Center at Morristown Memorial Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburg Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically proven ocular/cutaneous melanoma with liver-dominant unresectable metastatic disease, defined as limited extra-hepatic disease and hepatic involvement which would, in the Investigator's opinion, result in morbidity and eventual mortality. Limited extra-hepatic disease considered acceptable includes:

   • up to 4 pulmonary nodules, each <1cm in diameter
   • retroperitoneal lymph nodes <1cm in diameter
   • resectable skin or subcutaneous metastases
   • asymptomatic bone metastases that have been, or can be, palliated with external beam radiation therapy
   • a solitary metastasis to any site that can be resected with limited morbidity or controlled with radiation
2. ≥1 measurable hepatic lesion per RECIST 1.1
3. Vasculature compatible with insertion of CS-PHP catheters, per baseline abdominal MRA
4. ECOG PS 0-2

Exclusion Criteria:

1. Chemotherapy, radiotherapy, or biologic therapy for the malignancy ≤1 month prior to 1st CS-PHP-melphalan infusion
2. Extensive prior radiotherapy, defined as treatment to ≥50% of marrow-containing bones
3. Immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine, or long-term oral glucocorticoids taken currently or ≤3 mths prior to 1st CS-PHP-melphalan infusion
4. Received an investigational product ≤30 days prior to the 1st CS-PHP-melphalan infusion
5. History of orthotopic liver transplantation, untreated gastrinoma (i.e. gastric acid hypersecretion) or prior Whipple procedure
6. Not recovered from side effects of prior therapy to ≤ Grade 1 NCI CTCAE 4.03
7. Child's B or C cirrhosis, or clinical evidence of portal hypertension
8. Patients with >50% of liver replaced by tumor, histologic evidence of hepatic dysfunction seen by laparoscopic liver biopsy
9. History or evidence of clinically significant cardiac disease such as symptomatic arrhythmia, angina/ischemia, coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty, uncontrolled atrial fibrillation, CHF with a left ventricular ejection fraction <40%, uncontrolled hypertension (SBP >190 mmHg or DBP >100 mmHg), HR outside normal range of 50-100 bpm for women and 45-100 bpm for men
10. History/evidence of clinically significant pulmonary or cardiac disease incompatible with fitness to undergo general anesthesia
11. Uncontrolled diabetes mellitus or hypo/hyperthyroidism
12. Active uncontrolled infection
13. History of bleeding disorders or known unresolved venous shunting
14. Requirement for ongoing chronic anticoagulation
15. Evidence of intracranial abnormalities resulting in risk for bleeding with anticoagulation
16. History of alcohol or drug abuse ≤6 mths
17. Other malignancy within 3 yrs before enrollment with the exception of curatively treated basal or squamous cell carcinoma of the skin, or curatively treated cervical, breast carcinoma in situ or prostate cancer
18. History of hypersensitivity to: melphalan or its components; iodine contrast that cannot be controlled by premedication with antihistamines and steroids; latex
19. Known hypersensitivity to heparin in the presence of heparin-induced thrombocytopenia antibodies

20. Inadequate hematological or renal function as indicated by any of the following:

    • Platelets <100,000/mm3
    • Hb ≤10 g/dL
    • Neutrophils <2,000/mm3
    • S Creat >1.5 mg/dL or measured creatinine clearance <60 mL/min/1.73 m2

21. Inadequate liver function as indicated by any of the following:

    • Tbili ≥3.0 mg/dL
    • INR >1.5
    • AST/ALT >5xULN
22. Pregnant or nursing
23. Positive pregnancy test in subjects of childbearing potential ≤7 days prior to first CS-PHP-melphalan infusion
24. Women who are pre-menopausal (i.e. have had a menstrual period ≤12 months) who are unwilling or unable to undergo hormonal suppression to avoid menstruation during treatment
25. Sexually active females of childbearing potential and sexually active males with partners of reproductive potential unwilling or unable to use contraception from screening until at least 30 days after last administration of CS-PHP-melphalan

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: Delcath Systems Inc.
• Investigators: Principal Investigator: Charles W Nutting, DO, Sky Ridge Medical Center; Principal Investigator: Jonathan Zager, MD, H. Lee Moffitt Cancer Center and Research Institue at University of Southern Florida; Principal Investigator: Mark Faries, MD, Saint John's Cancer Institute; Principal Investigator: James F Pingpank, MD, Univeristy of Pittsburg Cancer Center; Principal Investigator: Eric D Whitman, MD, Carol G. Simon Cancer Center at Morristown Memorial Hospital; Principal Investigator: H. Richard Alexander, MD, University of Maryland Medical Center

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Registration Dates

• First Submitted: November 13, 2012
• First Submitted That Met QC Criteria: November 13, 2012
• First Posted (Estimate): November 16, 2012

Study Record Updates

• Last Update Posted (Estimate): October 23, 2013
• Last Update Submitted That Met QC Criteria: October 22, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Skin Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: MEL 2009-01