Chemoembolization of Uveal Melanoma Hepatic Metastases Using 300mg of BCNU Dissolved in Lipiodol® Followed by Gelfoam® Embolization
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Thomas Jefferson University
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Best response to treatment
Study Overview
Brief Summary
This phase II trial studies the effect of transarterial chemoembolization in treating patients with uveal melanoma that has spread to the liver (liver metastases). Transarterial chemoembolization involves the injection of a blocking agent (gelatin sponge, ethiodized oil) and a chemotherapy agent (carmustine) directly into the artery in the liver to treat liver cancers. Chemotherapy drugs, such as carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. transarterial chemoembolization with carmustine in combination with ethiodized oil and gelatin sponge may help cause the tumors in the liver to shrink or disappear.
Detailed Description
PRIMARY OBJECTIVE:
To determine the efficacy (clinical response) in terms of disease control rate (DCR) (complete response [CR] + partial response [PR] + stable disease [SD]) with chemoembolization of hepatic metastases with 300 mg of carmustine (BCNU) in ethiodized oil in metastatic uveal melanoma patients.
SECONDARY OBJECTIVES:
To investigate overall survival (OS) and progression-free survival (PFS) in uveal melanoma patients with hepatic metastases.
To assess the toxicity of the above treatment regimen.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed metastatic uveal melanoma in the liver
- •Tumor burden < 75%. Patients must have at least one tumor measuring >= 10 mm in longest diameter by magnetic resonance imaging (MRI) or triphasic computed tomography (CT) (if MRI is not available or contraindicated)
- •No prior transarterial catheter-directed therapies. Prior hepatic tumor ablation, hepatic radiation or liver resection will be permitted as long as growing measurable liver tumors exists. Prior systemic treatments are allowed as long as there are no outstanding toxicities greater than grade 1
- •Willingness and ability to give informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Serum creatinine =< 2.0 mg/dl
- •Bilirubin =< 2.0 mg/ml. Exceptions will be made for patients with diagnosed Gilbert's Syndrome. In this instance, a bilirubin level =< 3.0 mg/ml will be allowed for this patients with this syndrome
- •Albumin >= 3.0 g/dl
- •No ascites
- •Granulocyte count >= 1500/m^3
- •Platelet count >= 150,000/m^3
Exclusion Criteria
- •Less than 18 years of age
- •Previous liver-directed treatments including immunoembolization, chemoembolization, radioembolization, hepatic arterial perfusion, or drug-eluting beads
- •Presence of life-limiting extrahepatic metastasis that requires systemic treatment within 3 months. However, radiation treatment of extrahepatic metastases such as bone, lymph nodes or subcutaneous metastases will be permitted while the patient is on study. Zometa or X-Geva to treat bone metastases will also be permitted. Immune check-point inhibitors while on study will NOT be permitted
- •Portal vein occlusion, or inadequate collateral portal venous flow, as determined by MRI
- •Known active viral or autoimmune hepatitis requiring treatments with serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) equal or greater than 5 times normal
- •Presence of uncontrolled hypertension or congestive heart failure, or acute myocardial infarction within 6 months of entry
- •Presence of any other medical conditions that imply a survival of less than six months
- •Uncontrolled severe bleeding tendency or active gastrointestinal (GI) bleeding due to varices or main portal vein occlusion. Abnormal coagulation test must be corrected prior to the procedure
- •History of life-threatening allergic reaction to iodinated contrast or BCNU despite pre-treatment with steroids
- •Pregnant and/or breastfeeding women
- •Presence of known untreated brain metastases. If patients have had previous treatment for brain metastasis, an MRI or CT of the brain must confirm the stabilization of the brain metastasis for more than 4 weeks
- •Biliary obstruction, biliary stent, or prior biliary surgery including sphincterotomy but excluding cholecystectomy
Arms & Interventions
Treatment (carmustine, ethiodized oil, gelatin sponge)
Patients undergo TACE by receiving an infusion of carmustine dissolved in ethiodized oil and an injection of gelatin sponge. Treatment repeats Q4W for bilobar disease or Q7W for unilobar disease in the absence of disease progression or unacceptable toxicity or until maximum clinical benefit is obtained.
Intervention: Transarterial Chemoembolization (Procedure)
Treatment (carmustine, ethiodized oil, gelatin sponge)
Patients undergo TACE by receiving an infusion of carmustine dissolved in ethiodized oil and an injection of gelatin sponge. Treatment repeats Q4W for bilobar disease or Q7W for unilobar disease in the absence of disease progression or unacceptable toxicity or until maximum clinical benefit is obtained.
Intervention: Medical Device Usage and Evaluation (Other)
Treatment (carmustine, ethiodized oil, gelatin sponge)
Patients undergo TACE by receiving an infusion of carmustine dissolved in ethiodized oil and an injection of gelatin sponge. Treatment repeats Q4W for bilobar disease or Q7W for unilobar disease in the absence of disease progression or unacceptable toxicity or until maximum clinical benefit is obtained.
Intervention: Carmustine (Drug)
Treatment (carmustine, ethiodized oil, gelatin sponge)
Patients undergo TACE by receiving an infusion of carmustine dissolved in ethiodized oil and an injection of gelatin sponge. Treatment repeats Q4W for bilobar disease or Q7W for unilobar disease in the absence of disease progression or unacceptable toxicity or until maximum clinical benefit is obtained.
Intervention: Ethiodized Oil (Drug)
Outcomes
Primary Outcomes
Best response to treatment
Time Frame: After the completion of cycle 2 of chemoembolization (1 cycle = 4 or 7 weeks)
Response to treatment
Disease control rate (DCR) including complete response + partial response + stable disease
Time Frame: Up to 2 years
All estimates of rates (e.g., DCR) will be presented with corresponding confidence intervals. For DCR, the method of Atkinson and Brown will be used to allow for the two-stage design using the criteria adapted from the international criteria proposed by Response Evaluation Criteria in Solid Tumors 1.03.
Best response to treatment
Time Frame: After the completion of cycle 2 of chemoembolization (1 cycle = 4 or 7 weeks)
Response to treatment
Disease control rate (DCR) including complete response + partial response + stable disease
Time Frame: Up to 2 years
All estimates of rates (e.g., DCR) will be presented with corresponding confidence intervals. For DCR, the method of Atkinson and Brown will be used to allow for the two-stage design using the criteria adapted from the international criteria proposed by Response Evaluation Criteria in Solid Tumors 1.03.
Secondary Outcomes
- Time to progression(From the first chemoembolization to the time when progression of liver metastases is confirmed, assessed up to 2 years)
- Overall survival(From the first chemoembolization until death, assessed up to 2 years)
- Time to progression(From the first chemoembolization to the time when progression of liver metastases is confirmed, assessed up to 2 years)
- Overall survival(From the first chemoembolization until death, assessed up to 2 years)