Intraocular MelanomaPhase 3NCT00324727
Hepatic Arterial Infusion With Melphalan Compared With Standard Therapy in Treating Patients With Unresectable Liver Metastases Due to Melanoma
A Phase 3 study testing melphalan, regional chemotherapy and systemic chemotherapy in people with Intraocular Melanoma and Melanoma (Skin), run by Delcath Systems Inc. at 12 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving melphalan directly into the arteries around the tumor may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Intraocular Melanoma, Melanoma (Skin), Metastatic Cancer
- What is being tested?
- melphalan, regional chemotherapy and systemic chemotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 12 sitesUnited States
- Study dates
- Feb 2006to Aug 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed liver metastases secondary to cutaneous or ocular melanoma
- Unresectable disease
- Predominantly in the parenchyma of the liver
- Measurable disease by CT scan and/or MRI
- Limited unresectable extrahepatic disease allowed provided the life-limiting component of progressive disease is in the liver, including, but not limited to, any of the following:
- Up to 4 pulmonary nodules, each < 1 cm in diameter
- Retroperitoneal lymph nodes < 3 cm in diameter
- Less than 10 skin or subcutaneous metastases < 1 cm in diameter
- Asymptomatic bone metastases that are eligible for or have undergone palliative external-beam radiotherapy
- Solitary metastasis to any site that can be resected
PATIENT CHARACTERISTICS:
- Life expectancy ≥ 3 months
- ECOG performance status 0-2
- Bilirubin < 3.0 mg/dL
- PT within 2 seconds of upper limit of normal (ULN)
- AST/ALT ≤ 10 times ULN
- Platelet count > 75,000/mm^3
- Hematocrit > 27% (may be achieved with a transfusion)
- Absolute neutrophil count ≥ 1,300/mm^3
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
- Fertile patients must use effective contraception
- Not pregnant or nursing
- Negative pregnancy test
- No history of congestive heart failure
- LVEF ≥ 40%
- No significant chronic obstructive pulmonary disease (COPD) or other chronic pulmonary restrictive disease
- FEV_1 ≥ 30%
- DLCO ≥ 40% of predicted
- Weight ≥ 35 kg
- No untreated active bacterial infection with systemic manifestations (e.g., malaise, fever, and leucocytosis)
- No severe allergic reactions to iodine contrast unless reaction can be controlled by antihistamines and/or steroids
- No known hypersensitivity to melphalan
- No positive serology for HIV, hepatitis B surface antigen, or hepatitis C antibody (pharmacokinetics portion of the study only)
- No known latex allergy
- No Childs B or C cirrhosis
- No evidence of portal hypertension by history, endoscopy, or radiological study
- No prior history of gastrinoma
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 1 month since prior chemotherapy, radiotherapy, or biologic therapy for this cancer and recovered
- No prior regionally delivered melphalan
- No prior Whipple procedure
- No concurrent immunosuppressive therapy
- No concurrent chronic anticoagulation therapy
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Cancer Center of Albany Medical Center
Albany, New York, 12208
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, 21201
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, 20892-1182
St. Luke's Cancer Network at St. Luke's Hospital
Bethlehem, Pennsylvania, 18015
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210-1240
Swedish Medical Center
Englewood, Colorado, 80113
University of Texas Medical Branch
Galveston, Texas, 77555-0361
Carol G. Simon Cancer Center at Morristown Memorial Hospital
Morristown, New Jersey, 07962-1956
UPMC Cancer Centers
Pittsburgh, Pennsylvania, 15232
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, 97213-2967
John Wayne Cancer Institute at Saint John's Health Center
Santa Monica, California, 90404
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, 33612-9497
About this study
Official title: A Random-Assignment Study of Hepatic Arterial Infusion of Melphalan With Venous Filtration Via Peripheral Hepatic Perfusion (PHP) (Delcath System) Versus Best Alternative Care for Ocular and Cutaneous Melanoma Metastatic to the Liver
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving melphalan directly into the arteries around the tumor may kill more tumor cells. It is not yet known whether hepatic arterial infusion with melphalan is more effective than standard therapy in treating liver metastases due to melanoma.
PURPOSE: This randomized phase III trial is studying hepatic arterial infusion with melphalan to see how well it works compared to standard therapy in treating patients with unresectable liver metastases due to melanoma.
Read the detailed description
OBJECTIVES:
Primary
- Compare the hepatic progression-free survival of patients with unresectable liver metastases secondary to ocular or cutaneous melanoma treated with percutaneous isolated hepatic arterial perfusion (PHP) with melphalan with subsequent venous hemofiltration vs the best alternative standard treatment.
Secondary
- Determine the response rate and duration of response in patients treated with melphalan PHP.
- Determine the patterns of recurrence in patients treated with melphalan PHP.
- Compare the overall survival of patients treated with these regimens.
- Compare the safety and tolerability of these regimens in these patients.
- Determine the pharmacokinetics of melphalan after PHP.
OUTLINE: This is a multicenter study. Patients are stratified according to site of disease (ocular vs cutaneous). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo an isolated hepatic arterial infusion of melphalan over 30 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response undergo 2 additional courses in the absence of ongoing or increasing toxicity.
- Arm II: Patients receive the best alternative therapy comprising supportive care, systemic or regional chemotherapy, hepatic artery (chemo)-embolization, or any other appropriate therapy at the National Cancer Institute or therapy at the discretion of their physician. Patients may cross over to arm I if they have evidence of disease progression.
Blood samples are collected periodically for pharmacokinetic analysis of melphalan.
After completion of study treatment, patients are followed periodically for 4 years and then annually for survival.
PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.
- Conditions
- Intraocular Melanoma, Melanoma (Skin), Metastatic Cancer
- Being tested
- melphalan, regional chemotherapy, systemic chemotherapy, hepatic artery embolization
- Keywords
- liver metastases, extraocular extension melanoma, stage IV melanoma, recurrent melanoma, recurrent intraocular melanoma, metastatic intraocular melanoma, iris melanoma, ciliary body and choroid melanoma, medium/large size
- Medical subject headings
- Uveal Melanoma, Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
melphalanDrug
Given throug isolated hepatic artery infusion
regional chemotherapyDrug
Patients receive the best alternative therapy
systemic chemotherapyDrug
Patients receive the best alternative therapy
hepatic artery embolizationProcedure or surgery
Patients receive the best alternative therapy
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients undergo an isolated hepatic arterial infusion of melphalan over 30 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response undergo 2 additional courses
in the absence of ongoing or increasing toxicity. Receives: Drug: melphalan |
| Arm II | Active comparator | Patients receive the best alternative therapy comprising supportive care, systemic or regional chemotherapy, hepatic artery (chemo)-embolization, or any other appropriate therapy at the National Cancer Institute or therapy at the discretion of their physician.
Patients may cross over to arm I if they have evidence of disease progression. Receives: Drug: regional chemotherapy; Drug: systemic chemotherapy; Procedure: hepatic artery embolization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic progression free survival
Measured: Treatment to time of progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2006 (estimated)
- Study startFeb 2006
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intraocular MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Delcath Systems Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Marybeth S. Hughes, MD, Principal investigator, NCI - Surgery Branch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00324727
- Sponsor's protocol ID
- CDR0000468944
- Other IDs
- NCI-06-C-0088, NCI-P6701
- Status last verified
- Jun 2021
- First submitted
- 10 May 2006
- Last updated
- 21 Jun 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Random-Assignment Study of Hepatic Arterial Infusion of Melphalan With Venous Filtration Via Peripheral Hepatic Perfusion (PHP) (Delcath System) Versus Best Alternative Care for Ocular and Cutaneous Melanoma Metastatic to the Liver
- ClinicalTrials.gov ID
- NCT00324727
- Acronym / sponsor ID
- CDR0000468944
- Conditions
- Intraocular Melanoma, Melanoma (Skin), Metastatic Cancer
- Keywords
- liver metastases, extraocular extension melanoma, stage IV melanoma, recurrent melanoma, recurrent intraocular melanoma, metastatic intraocular melanoma, iris melanoma, ciliary body and choroid melanoma, medium/large size
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Delcath Systems Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2006
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 11 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving melphalan directly into the arteries around the tumor may kill more tumor cells. It is not yet known whether hepatic arterial infusion with melphalan is more effective than standard therapy in treating liver metastases due to melanoma.
PURPOSE: This randomized phase III trial is studying hepatic arterial infusion with melphalan to see how well it works compared to standard therapy in treating patients with unresectable liver metastases due to melanoma.
Detailed description
OBJECTIVES:
Primary
- Compare the hepatic progression-free survival of patients with unresectable liver metastases secondary to ocular or cutaneous melanoma treated with percutaneous isolated hepatic arterial perfusion (PHP) with melphalan with subsequent venous hemofiltration vs the best alternative standard treatment.
Secondary
- Determine the response rate and duration of response in patients treated with melphalan PHP.
- Determine the patterns of recurrence in patients treated with melphalan PHP.
- Compare the overall survival of patients treated with these regimens.
- Compare the safety and tolerability of these regimens in these patients.
- Determine the pharmacokinetics of melphalan after PHP.
OUTLINE: This is a multicenter study. Patients are stratified according to site of disease (ocular vs cutaneous). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo an isolated hepatic arterial infusion of melphalan over 30 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response undergo 2 additional courses in the absence of ongoing or increasing toxicity.
- Arm II: Patients receive the best alternative therapy comprising supportive care, systemic or regional chemotherapy, hepatic artery (chemo)-embolization, or any other appropriate therapy at the National Cancer Institute or therapy at the discretion of their physician. Patients may cross over to arm I if they have evidence of disease progression.
Blood samples are collected periodically for pharmacokinetic analysis of melphalan.
After completion of study treatment, patients are followed periodically for 4 years and then annually for survival.
PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: melphalanPatients undergo an isolated hepatic arterial infusion of melphalan over 30 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response undergo 2 additional courses in the absence of ongoing or increasing toxicity. |
| Arm II | Active comparator | Drug: regional chemotherapy, Drug: systemic chemotherapy, Procedure: hepatic artery embolizationPatients receive the best alternative therapy comprising supportive care, systemic or regional chemotherapy, hepatic artery (chemo)-embolization, or any other appropriate therapy at the National Cancer Institute or therapy at the discretion of their physician. Patients may cross over to arm I if they have evidence of disease progression. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| melphalanGiven throug isolated hepatic artery infusion | Drug | Arm I |
| regional chemotherapyPatients receive the best alternative therapy | Drug | Arm II |
| systemic chemotherapyPatients receive the best alternative therapy | Drug | Arm II |
| hepatic artery embolizationPatients receive the best alternative therapy | Procedure or surgery | Arm II |
Primary outcome
Hepatic progression free survival
Time frame: Treatment to time of progression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2021.
- Publication of ResultsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marybeth S. Hughes, MD principal investigator
NCI - Surgery Branch
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing melphalan, regional chemotherapy and systemic chemotherapy in people with Intraocular Melanoma and Melanoma (Skin), run by Delcath Systems Inc. at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic progression free survival (time frame: Treatment to time of progression). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2021.