Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Percutaneous Hepatic Perfusion vs Best Alternative Care in Patients With Hepatic-dominant Ocular Melanoma

Protocol: OSU-16073

Full Title

A Randomized, Controlled, Phase 3 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Melphalan/HDS Treatment in Patients with Hepatic-Dominant Ocular Melanoma

Purpose

This study will evaluate two groups of patients who have melanoma that has spread from the

eye to the liver: one group (50%) will get high-dose chemotherapy delivered specifically to

the liver, while the other group (50%) will get one of 4 standard best alternative care

treatments. Patients in each group will get repeating cycles of treatment until the cancer

in the liver advances and will be followed until death. This study will evaluate the effect

of the treatments on how long patients live and how long it takes for the cancer to advance

or respond to the treatment.

Study Objective

The study will consist of 3 phases: a screening phase, treatment phase, and follow-up phase.

Screening Phase: Screening assessments will be conducted within 28 days prior to

randomization to determine each patient's overall eligibility. These assessments will

include medical history, physical examination, Eastern Cooperative Oncology Group (ECOG)

performance status (PS), 12 lead electrocardiogram (ECG), echocardiogram (ECHO), vital

signs, full hematology and biochemistry, radiologic assessments of disease status, and an

evaluation of the vasculature compatibility for Percutaneous Hepatic Perfusion (PHP).

Treatment Phase: Eligible patients will be randomized to treatment with Melphalan/HDS 3.0

mg/kg Ideal Body Weight (IBW) or Best Alternative Care (BAC) and must begin treatment within

14 days following randomization. BAC treatment will be: dacarbazine (DTIC); transarterial

chemoembolization (TACE); ipilimumab; or pembrolizumab, based on each institution's rank

order of their BAC treatments based on their standard of care (SOC). For Melphalan/HDS

treatment, patients will receive up to 6 treatments. Each treatment cycle consists of 6

weeks with an acceptable delay for another 2 weeks before the next planned treatment to

allow for recovery of melphalan-related toxicity, if needed. Tumor response will be assessed

in both cohorts every 12 weeks (+ 2 weeks) until hepatic disease progression. If the patient

receives only 1 treatment, the disease assessment scans will be conducted 12 weeks after the

date of the first treatment. The assessment scans will be reviewed by an Independent Review

Committee (IRC), also referred to as Independent Central Review. At any time when hepatic

progressive disease (PD) is observed, the patient will be removed from further study

treatment. Melphalan/HDS treatment will also be discontinued in the event that recovery from

treatment related toxicity requires more than 8 weeks from last treatment. An

end-of-treatment visit will be conducted approximately 6 to 8 weeks following the final dose

of study treatment. Ongoing adverse events (AEs) at the end-of-treatment visit will be

followed until the severity returns to baseline of CTCAE Grade < 1. The maximum possible

duration of the study treatment for any patient will be 12 months.

Follow-up Phase: In the event that disease has not progressed at the end-of-treatment visit,

disease assessment scans will continue every 12 weeks (+ 2 weeks) until disease progression

is documented. Patients will be contacted by phone every 6 months for survival status for

the first two years following the completion of study treatment, then yearly thereafter,

until death, withdrawal of informed consent or they become lost to follow-up, whichever

occurs first. Patients will be monitored for two years, following the completion of study

treatment, for the development of myelodysplasia and secondary leukemia.

Are you eligible?

Inclusion Criteria:

Inclusion Criteria:

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 not have chemotherapy, radiotherapy, chemoembolization,

radioembolization, or immunoembolization 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 (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.

11. Provided signed informed consent.

Exclusion Criteria:

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 (β-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 6 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 wit

Exclusion Criteria:

Inclusion Criteria:

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 not have chemotherapy, radiotherapy, chemoembolization,

radioembolization, or immunoembolization 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 (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.

11. Provided signed informed consent.

Exclusion Criteria:

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 (β-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 6 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 wit

Ocular Melanoma