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

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