LC Bead Embolization Agent With Doxorubicin in the Treatment Liver Metastasis From Melanoma (DEBDOX)

Transcatheter Arterial Chemoembolization With Doxorubicin-loaded LC Beads in the Treatment of Liver-dominant Metastases in Patients With Stage IV Metastatic Melanoma

The purpose of this study is to determine if LC beads loaded with Doxorubicin are a safe and effective treatment for melanoma that has spread to the liver.

Study Overview

• Status: Completed
• Conditions: Stage IV Melanoma
• Intervention / Treatment: Device: LC beads loaded with Doxorubicin

Detailed Description

In this study, trans-arterial chemoembolization will be used to deliver LC beads loaded with Doxorubicin directly into liver tumors resulting from malignant melanoma.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • Houston, Texas, United States, 77230
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with unresectable, measurable disease defined as at least one lesion that can be accurately and serially measured per the modified RECIST and EASL criteria (2D/3D-EASL) or MRI (Extent of Necrosis)
• Patients ≥ 18 years of age, > 35kg, of any race or sex, who have histological or radiological proof of melanoma to the liver
• ECOG performance status < 3
• Patient chooses to participate and has signed the informed consent document
• Patients with unilobar disease who can be treated superselectively in a single session or patients with bilobar disease who can have both lobes able to be treated within 3 - 4 weeks in separate sessions
• Patients with patent main portal vein
• Ocular melanoma is allowed
• Patients with clinically and radiologically stable brain metastasis from melanoma can be included
• Patients with liver dominant disease (>50% overall tumor burden)
• Prior systemic therapy for metastatic disease is allowed
• Non-pregnant with an acceptable contraception in premenopausal women and fertile men
• Hematological function: ANC ≥1.5 x 109/L, platelets ≥ 75 x 109/L, INR ≤1.3 (patients on therapeutic anticoagulants are not eligible)
• Adequate renal function: Creatinine ≤2.0mg/dl and GFR >30
• Adequate liver function: total bilirubin ≤ 2.5 mg/dl, ALT, AST ≤ 5 times ULN, albumin ≥ 2.5mg/dl
• All toxic effects of prior therapy must have resolved to ≤ Grade 1 unless otherwise specified above

Exclusion Criteria:

• Women who are pregnant or breast feeding
• Patients eligible for curative treatment such as resection or radiofrequency ablation
• Active bacterial, viral or fungal infection within 72 hours of study entry
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis & Ti) or any cancer curatively treated < 5 years prior to study entry
• Contraindication to hepatic artery embolization procedures:
• Severe peripheral vascular disease precluding catheterization
• Large shunt as determined by the investigator (pretesting with TcMAA not required) at the time of first angiogram
• Hepatofugal blood flow
• Main portal vein occlusion (e.g. thrombus or tumor)
• Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment.
• Allergy to contrast media that cannot be managed with standard care (e.g. steroids), making magnetic resonance imaging (MRI) or computed tomography (CT) contraindicated
• Advanced liver disease (> 80% liver replacement)
• Other significant medical or surgical condition, or any medication or treatment that would place the patient at undue risk and that would preclude the safe use of chemoembolization or would interfere with study participation
• Any contraindication for doxorubicin administration:
• WBC <3000 cells/mm3
• Neutrophils <1500 cells/mm3
• Deficient cardiac function defined as a LVEF of <50% normal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcatheter Arterial Chemoembolization; TACE using LC beads loaded with Doxorubicin	Device: LC beads loaded with Doxorubicin; During each TACE, 2 vials (1 vial, 75mg Doxorubicin) of 100-300 micrometer size LC beads loaded with doxorubicin will be delivered to the liver tumor(s). Total Doxorubicin dose for each TACE is 150mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	Adverse events were collected from all 20 subjects.	Date of surgery through 2 years post procedure or until patient death

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Tumor Response	Progression is determined using Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Progressive disease is defined as at least 20% increase in the sum of the longest target lesions, taking as reference the smallest sum longest diameter recorded since start of treatment OR appearance of one or more new lesions greater then 1cm in size. Percentage of tumor response will be assessed up to 1 year post treatment.	Percentage of tumor response assessed up to 1 year post treatment.

Collaborators and Investigators

• Sponsor: Robert C. Martin
• Collaborators: M.D. Anderson Cancer Center; Thomas Jefferson University; University of Louisville
• Investigators: Study Director: Robert CG Martin, MD, PhD, University of Louisville

Publications and helpful links

General Publications

• Rostas JW, Tam AL, Sato T, Scoggins CR, McMasters KM, Martin RCG 2nd. Health-related quality of life during trans-arterial chemoembolization with drug-eluting beads loaded with doxorubicin (DEBDOX) for unresectable hepatic metastases from ocular melanoma. Am J Surg. 2017 Nov;214(5):884-890. doi: 10.1016/j.amjsurg.2017.07.007. Epub 2017 Jul 21.
• Rostas J, Tam A, Sato T, Kelly L, Tatum C, Scoggins C, McMasters K, Martin RCG 2nd. Image-Guided Transarterial Chemoembolization With Drug-Eluting Beads Loaded with Doxorubicin (DEBDOX) for Unresectable Hepatic Metastases from Melanoma: Technique and Outcomes. Cardiovasc Intervent Radiol. 2017 Sep;40(9):1392-1400. doi: 10.1007/s00270-017-1651-z. Epub 2017 May 15.

Helpful Links

• Watch our metastatic melanoma to the liver clinical trial video

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: November 4, 2009
• First Submitted That Met QC Criteria: November 6, 2009
• First Posted (Estimate): November 10, 2009

Study Record Updates

• Last Update Posted (Actual): October 25, 2018
• Last Update Submitted That Met QC Criteria: September 28, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: stage IV melanoma; metastatic melanoma; metastatic melanoma to the liver
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: G090097