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Transarterial Chemoembolization for the Treatment of Uveal Melanoma With Liver Metastases

Primary Purpose

Metastatic Malignant Neoplasm in the Liver, Metastatic Uveal Melanoma, Stage IV Choroidal and Ciliary Body Melanoma AJCC V8

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Carmustine

Ethiodized Oil

Transarterial Chemoembolization

Medical Device Usage and Evaluation

About this trial

This is an interventional treatment trial for Metastatic Malignant Neoplasm in the Liver

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Sidney Kimmel Cancer Center at Thomas Jefferson UniveristyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (carmustine, ethiodized oil, gelatin sponge)

Arm Description

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.

Outcomes

Primary Outcome Measures

Best response to treatment

Response to treatment

Disease control rate (DCR) including complete response + partial response + stable disease

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 Outcome Measures

Time to progression

Will be estimated by the Kaplan-Meier method.

Overall survival

Will be estimated by the Kaplan-Meier method. Date and cause of death will be recorded. The cause of death will be categorized as either cancer-related or cancer unrelated.

Incidence of adverse events

Safety will be assessed and the toxicity of the treatment will be monitored using the National Cancer Institute Common Toxicity Criteria version 5. All estimates of rates (e.g., toxicity) will be presented with corresponding confidence intervals.

Full Information

NCT ID

NCT04728633

First Posted

January 25, 2021

Last Updated

September 29, 2023

Sponsor

Thomas Jefferson University

1. Study Identification

Unique Protocol Identification Number

NCT04728633

Brief Title

Transarterial Chemoembolization for the Treatment of Uveal Melanoma With Liver Metastases

Official Title

Chemoembolization of Uveal Melanoma Hepatic Metastases Using 300mg of BCNU Dissolved in Lipiodol® Followed by Gelfoam® Embolization

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 27, 2021 (Actual)

Primary Completion Date

June 30, 2025 (Anticipated)

Study Completion Date

March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Thomas Jefferson University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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. OUTLINE: Patients undergo transarterial chemoembolization (TACE) by receiving an infusion of carmustine dissolved in ethiodized oil and an injection of gelatin sponge. Treatment repeats once every 4 weeks (Q4W) for bilobar disease or once every 7 weeks (Q7W) for unilobar disease in the absence of disease progression or unacceptable toxicity or until maximum clinical benefit is obtained. After completion of study treatment, patients are followed up at 30 days, and then every 2 months for up to 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Malignant Neoplasm in the Liver, Metastatic Uveal Melanoma, Stage IV Choroidal and Ciliary Body Melanoma AJCC V8

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (carmustine, ethiodized oil, gelatin sponge)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Carmustine

Other Intervention Name(s)

1,3-Bis(2-chloroethyl)-1-nitrosourea, 1,3-Bis(beta-chloroethyl)-1-nitrosourea, BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, WR-139021, SRI 1720, SK 27702, Nitrumon, Nitrourean, N,N''-Bis(2-chloroethyl)-N-nitrosourea, FDA 0345, Carmustinum, Carmustin

Intervention Description

Given via infusion

Intervention Type

Drug

Intervention Name(s)

Ethiodized Oil

Other Intervention Name(s)

Lipiodol, Iodized Oil, Ethiodol, ETHIODIZED OIL,, 8008-53-5

Intervention Description

Given via infusion

Intervention Type

Procedure

Intervention Name(s)

Transarterial Chemoembolization

Other Intervention Name(s)

TACE

Intervention Description

Undergo TACE

Intervention Type

Other

Intervention Name(s)

Medical Device Usage and Evaluation

Intervention Description

Given gelatin sponge via injection

Primary Outcome Measure Information:

Title

Best response to treatment

Description

Response to treatment

Time Frame

After the completion of cycle 2 of chemoembolization (1 cycle = 4 or 7 weeks)

Title

Disease control rate (DCR) including complete response + partial response + stable disease

Description

Time Frame

Up to 2 year

Secondary Outcome Measure Information:

Title

Time to progression

Description

Will be estimated by the Kaplan-Meier method.

Time Frame

From the first chemoembolization to the time when progression of liver metastases is confirmed, assessed up to 2 years

Title

Overall survival

Description

Will be estimated by the Kaplan-Meier method. Date and cause of death will be recorded. The cause of death will be categorized as either cancer-related or cancer unrelated.

Time Frame

From the first chemoembolization until death, assessed up to 2 years

Title

Incidence of adverse events

Description

Time Frame

Up to 30 days after the last day of study participation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Carin Gonsalves, MD

Phone

215-955-6385

Carin.Gonsalves@jefferson.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carin Gonsalves, MD

Organizational Affiliation

Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sidney Kimmel Cancer Center at Thomas Jefferson Univeristy

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Carin Gonsalves, MD

Phone

215-955-6385

Carin.Gonsalves@jefferson.edu

12. IPD Sharing Statement

Learn more about this trial

Transarterial Chemoembolization for the Treatment of Uveal Melanoma With Liver Metastases

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