A Randomized, Controlle, Phase 3 study to evaluete the efficacy, safety and pharmacokinetics of Melphalan/HDS treatment in Patients with cancer of the eye that has spread to the liver
- Conditions
- Hepatic-Dominant Ocular MelanomaMedDRA version: 20.0Level: PTClassification code 10068117Term: Metastatic ocular melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-000417-44-IT
- Lead Sponsor
- DELCATH SYSTEMS, INCORPORATIONS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
1. Male or female patients = 18 years of age.
2. 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).
3. 50% or less histologically or cytologically-proven ocular melanoma metastases in the parenchyma of the liver.
4. Disease in the liver must be measurable by computed tomography (CT) and/or magnetic resonance imaging (MRI).
5. Evidence of limited extrahepatic disease on preoperative radiological studies is acceptable if
the life threatening component of PD is in the liver. Limited extrahepatic disease is defined in
this protocol as follows: metastasis in up to one other organ (bone, subcutaneous, or pulmonary),
limited to up to 2 nodules and amenable to resection or radiation. The extrahepatic lesions
should be no larger than 2 cm in diameter each. The rationale for permitting this limited extrahepatic disease is that these types of lesions are amenable to surgical resection or radiation.
6. 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.
7. Patients must have had no chemotherapy or radiotherapy for their malignancy in the month 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.
8. Patients must have an ECOG PS of 0-1 at screening and on the day prior to treatment.
9. 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.
10. 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.
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 192
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48
Patients who meet any of the following criteria will be excluded from study entry:
1. Patients with Child-Pugh Class B or C cirrhosis or with evidence of portal hypertension by history, endoscopy, or radiologic
studies.
2. 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.
3. History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
4. For female patients of childbearing potential (i.e., have had a menstrual period within the past 12 months): unwilling or unable
to undergo hormonal suppression to avoid menstruation during treatment.
5. For female patients of childbearing potential (i.e. have had a menstrual period within the past 12
months): a positive serum pregnancy test (ß-human chorionic gonadotropin) within 7 days prior to enrollment.
6. Sexually active females of childbearing potential and sexually active males with partners of reproductive potential: unwilling or
unable to use appropriate contraception from screening until
at least 4 months after last administration of study treatment.
7. Lactating women are excluded from study participation.
8. Patients taking immunosuppressive drugs or who are unable to be temporarily removed from chronic anti-coagulation therapy.
9. Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until
completion of appropriate therapy.
10. 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).
11. Patients with a history of or known hypersensitivity to melphalan or the components of the Melphalan/HDS system.
12. Patients previously treated with any intra-arterial regional hepatic therapy.
13. Patients with latex allergy.
14. Patients with a history of hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
15. 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).
16. Patients with a history of gastrinoma, hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or
known unresolved venous shunting.
17. Known varices at risk of bleeding, including medium or large esophageal or gastric varices, or
active peptic ulcer.
18. Patients with prior Whipple’s procedure.
19. Patients with brain metastases or presence of other intracranial lesions at risk for bleeding by
history or baseline radiologic imaging. Active infection, including Hepatitis B and Hepatitis C
infection. Patients with anti-hepatitis B core antibody (HBc) positive, or hepatitis B surface antigen (HBsAg) but DNA negative are
exception(s).
20. Uncontrolled endocrine disorders including diabetes mellitus, hypothyroidism, or hyperthyroidism.
21. Received any investigational agent for any indication within 30 days prior to first treatment.
22. Not recovered from side effects of prior therapy to = Grade 1 (according to National Cancer Institute (NCI) Comm
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare overall survival (OS) in patients with hepatic-dominant metastatic ocular melanoma;Secondary Objective: To compare the overall progression-free survival (PFS) (as determined by the Investigator) of<br>patients with hepatic-dominant metastatic ocular melanoma treated with Melphalan/HDS versus<br>control (BAC).<br><br>To compare the objective response rate (ORR = complete + partial response) (as determined by<br>the Investigator) of treatment with Melphalan/HDS versus control (BAC) in patients with hepatic-dominant metastatic ocular melanoma;Primary end point(s): To compare overall survival (OS) in<br>patients with hepatic-dominant metastatic ocular melanoma treated with Melphalan/HDS versus best alternative care (BAC).;Timepoint(s) of evaluation of this end point: The study endpoint will be measured at the conclusion of Melphalan/HDS treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Progression Free Survival (PFS) as determined by the Investigator<br>- Objective Response Rate (ORR) (complete response + partial response) as determined by the Investigator;Timepoint(s) of evaluation of this end point: In the event that disease has not progressed at the end-of-treatment visit, disease assessment scans will continue<br>every 12 weeks (+ 2 weeks) until disease progression is documented. Patients will be<br>contacted by phone every 6 months for survival status for the first two years following the completion of study treatment, then<br>yearly thereafter, until death, withdrawal of informed consent or they become<br>lost to follow-up, whichever occurs first