Stage IV Melanoma
Conditions
Keywords
metastatic melanoma, stage IV melanoma, metastatic melanoma to the liver
Brief summary
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.
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.
Interventions
DEVICELC 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
Sponsors
University of Louisville
Thomas Jefferson University
M.D. Anderson Cancer Center
Robert C. Martin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Date of surgery through 2 years post procedure or until patient death | Adverse events were collected from all 20 subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Tumor Response | Percentage of tumor response assessed up to 1 year post treatment. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transcatheter Arterial Chemoembolization TACE using LC beads loaded with Doxorubicin
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 | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Transcatheter Arterial Chemoembolization |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 19 / 20 |
Outcome results
Primary
Incidence of Adverse Events
Adverse events were collected from all 20 subjects.
Time frame: Date of surgery through 2 years post procedure or until patient death
Population: Participants who received at least one dose of LC beads with doxorubin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm | Incidence of Adverse Events | 465 Events |
Secondary
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.
Time frame: Percentage of tumor response assessed up to 1 year post treatment.
Population: Those who receive at least one dose of LC bead with doxorubin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Arm | Percentage of Tumor Response | 2.46 percentage of tumor response |