Metastatic Ocular MelanomaPhase 3NCT05022901
An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular Melanoma
A Phase 3 study testing Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS) in people with Metastatic Ocular Melanoma and Metastatic Uveal Melanoma, run by Delcath Systems Inc. at 5 sites in United States.
Trial summary
Patients in the study will be treated with Melphalan/HDS and will receive up to 6 total treatments. This study will evaluate the safety and effects of the treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Ocular Melanoma, Metastatic Uveal Melanoma
- What is being tested?
- Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesUnited States
- Study dates
- 10 Jun 2022to 1 Mar 2024
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients ≥ 18 years of age.
- Patients must weigh ≥ 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic Delivery System).
- 50% or less histologically or cytologically-proven ocular melanoma metastases in the parenchyma of the liver.
- Disease in the liver must be measurable by computed tomography (CT) and/or magnetic resonance imaging (MRI).
- Evidence of limited extrahepatic disease on preoperative radiological studies is acceptable if the life-threatening component of disease is in the liver. Limited extrahepatic disease is defined in this protocol as follows: metastasis in bone, subcutaneous, lung or lymph nodes that is amenable to resection or radiation and has a defined treatment plan. Patients with extra-hepatic tumor burden which does not have a defined treatment plan (i.e. monitor or is unable to be resected or radiated) must not be included in the trial.
- Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within 28 days prior to eligibility. An MRI of the liver is required at screening to validate that CT accurately reflects the extent of disease in the liver. For patients with MRI intolerance, a 3-phase liver CT is to be done in place of liver MRI.
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- Patients must not have had chemotherapy, radiotherapy, chemoembolization, radioembolization, or immunoembolization for their malignancy within 30 days prior to treatment and must have recovered from all side effects of therapeutic and diagnostic interventions except those listed in Appendix B of the study protocol.
- Patients receiving anti programmed cell death protein 1 (PD-1) immunotherapy such as pembrolizumab or nivolumab, or human cytotoxic T-lymphocyte antigen 4 blocking antibody such as ipilimumab must have completed treatment 8 weeks prior to study eligibility.
- Patients must have an ECOG PS of 0-1 at screening.
- Patients must have adequate hepatic function as evidenced by total serum bilirubin ≤1.5 x the upper limit of normal (ULN) and a prothrombin time (PT) within 2 seconds of the upper normal limit. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) must be ≤ 2.5 x ULN.
- Patients must have a platelet count > 100,000/µL, hemoglobin ≥ 10.0 gm/dL, white blood cell count (WBC) > 2,000/uL, absolute neutrophil count ≥ 1.5 x 109/L, and a serum creatinine ≤ 1.5 mg/dL unless the measured creatinine clearance is > 40 mL/min/1.73 m2.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (β-human chorionic gonadotropin) within 7 days prior to eligibility.
- Provided signed informed consent.
Who cannot join
- Patients with Child-Pugh Class B or C cirrhosis or with evidence of portal hypertension by history, endoscopy, or radiologic studies.
- Those with New York Heart Association functional classification II, III or IV active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
- History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
- Women of childbearing potential (WOCBP) i.e. fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months) unable to undergo hormonal suppression to avoid menstruation during treatment.
- WOCBP and fertile males (not permanently sterile by bilateral orchiectomy) unwilling or unable to use highly effective contraception method from consent to at least 6 months after the last administration of study treatment (e.g. combined hormonal contraception; progestogen-only hormonal contraception; Intrauterine device, intrauterine hormone-releasing system; bilateral tubal occlusion, vasectomized partner or sexual abstinence).
- Females that are pregnant or are breastfeeding.
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- Patients taking immunosuppressive drugs; however, oral corticosteroids ≤ 10 mg/ day are allowed.
- Patients who are unable to be temporarily removed from chronic anti-coagulation therapy.
- Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until completion of appropriate therapy.
- Patients with severe allergic reaction to iodine contrast, which cannot be controlled by premedication with antihistamines and steroids.
- Patients with a history of or known hypersensitivity to melphalan or the components of the Melphalan/HDS system.
- Patients with latex allergy.
- Patients with a history of hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
- Patients with a history of bleeding disorders or evidence of intracranial abnormalities which would put them at risk for bleeding with anti-coagulation (e.g., strokes, active metastases).
- Patients with a history of gastrinoma, NOTE: For patients with a history of liver surgery or major vasculature surgery, a CT angiogram or MR angiogram is required during screening to assure the patient does not have hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting.
- Known varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer.
- Patients with prior Whipple's procedure.
- Patients with brain metastases or presence of other intracranial lesions at risk for bleeding by history or baseline radiologic imaging.
- Patients with an active infection, including Hepatitis B and Hepatitis C infection. Patients with anti-hepatitis B core antibody (HBc) positive, or hepatitis B surface antigen (HBsAg) but DNA negative are exception(s).
- Uncontrolled endocrine disorders including diabetes mellitus, hypothyroidism, or hyperthyroidism.
- Received any investigational agent for any indication within 30 days prior to first treatment.
- Not recovered from side effects of prior therapy to ≤ Grade 1 (according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Certain side effects that are unlikely to develop into serious or life-threatening events (e.g. alopecia) are allowed at > Grade 1.
- Cancers other than ocular melanoma for which the patient is currently under treatment or still deemed to be not cancer free.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
The Ohio State University
Columbus, Ohio, 43221
Duke University Medical Center
Durham, North Carolina, 27710
University of Tennessee Health Science Center
Memphis, Tennessee, 38163
Stanford Cancer Institute
Palo Alto, California, 94304
Moffitt Cancer Center
Tampa, Florida, 12902
About this study
Patients in the study will be treated with Melphalan/HDS and will receive up to 6 total treatments.
This study will evaluate the safety and effects of the treatment.
Read the detailed description
The study will consist of 3 phases:
Screening/Baseline Phase: Screening assessments will be conducted within 28 days prior to the eligibility date to determine each patient's overall eligibility and baseline characteristics. These assessments will include medical history, physical examination, Eastern Cooperative Oncology Group (ECOG) performance status (PS), Quality of Life questionnaire, 12 lead electrocardiogram (ECG), echocardiogram (ECHO), vital signs, full hematology and biochemistry, Quality of Life questionnaire, radiologic assessments of baseline disease status and concomitant medications.
For patients with a history of liver surgery or major vasculature surgery, an angiogram evaluation of their vasculature will be performed for compatibility for Percutaneous Hepatic Perfusion (PHP) prior to confirming eligibility.
Eligibility date: This is the date on which all screening assessments have been completed and the patient is determined to be eligible for the trial.
Treatment Phase: The first study treatment should occur within 14 days of the eligibility date. Eligible patients will be treated with Melphalan/HDS 3.0 mg/kg Ideal Body Weight (IBW). Melphalan/HDS treatment will be administered every 6 weeks for a total of 6 cycles with an acceptable delay of another 2 weeks before the next planned treatment to allow for recovery of melphalan-related toxicity, if needed. Tumor response will be assessed every 12 weeks (+ 2 weeks) until disease progression. Patients with progressive disease (PD) will be discontinued from study treatment, and will continue to be followed until death. Melphalan/HDS treatment will also be discontinued if recovery from treatment related toxicity requires more than 8 weeks from the last treatment. An end-of-treatment visit (EOT) will be conducted approximately 6 to 8 weeks following the final study treatment.
Follow-up Phase: Once the patient has completed the end-of-treatment (EOT) visit in accordance with the schedule of events they will enter the follow-up phase. If the disease has not progressed at the EOT, the patient will need to continue with disease assessment visits every 12 weeks (± 2 weeks) until disease progression is documented. After disease progression, follow-up is to be by phone every 3 months for survival status until death.
- Being tested
- Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS)
- Keywords
- percutaneous hepatic perfusion, PHP, uveal melanoma, HEPZATO
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS)Combination product
Also called percutaneous hepatic perfusion, PHP, HEPZATO
Melphalan administered directly to the liver via the Hepatic Delivery System (HDS) infused over a 30 minute period, followed by a 30 minute washout period
| Study group | Role | What they receive |
|---|---|---|
| Melphalan/HDS | Experimental | Eligible patients will be treated with Melphalan/HDS 3.0 mg/kg Ideal Body Weight (IBW). Melphalan/HDS treatment will be administered every 6 weeks for a total of 6 cycles with an acceptable delay of another 2 weeks before the next planned treatment to allow for recovery of melphalan-related toxicity, if needed. Receives: Combination Product: Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
The number and type of adverse events will be assessed per CTCAE version 5.0.
Measured: From eligibility until death due to any cause, for up to 104 weeks
Secondary outcomes (4)
Efficacy (ORR)
Defined as the proportion of patients with a best overall response (BOR) based on a confirmed complete response or partial response (CR+PR) determined by the investigator per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Measured: Every 12 (+/-2) weeks until progression, for up to 104 weeks
Efficacy (OS)
The time from the eligibility date to date of death due to any cause
Measured: From eligibility until death due to any cause, for up to 104 weeks
Efficacy (PFS)
The time from the eligibility date to the first documented progression or death due to any cause determined by the investigator
Measured: Every 12 (+/-2) weeks until progression, for up to 104 weeks
Quality of Life (FHSI-8)
FHSI-8 Quality of Life Survey
Measured: Every 6-8 weeks until the end of treatment, for up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2021
- Study start10 Jun 2022
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Ocular 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Delcath Systems Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05022901
- Sponsor's protocol ID
- PHP-OCM-501
- Status last verified
- Dec 2023
- First submitted
- 18 Aug 2021
- Last updated
- 21 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular Melanoma
- ClinicalTrials.gov ID
- NCT05022901
- Acronym / sponsor ID
- PHP-OCM-501
- Keywords
- percutaneous hepatic perfusion, PHP, uveal melanoma, HEPZATO
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Delcath Systems Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Jun 2022 (actual)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Mar 2024 (estimated)
- First posted
- 26 Aug 2021 (actual)
- 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.
Patients in the study will be treated with Melphalan/HDS and will receive up to 6 total treatments.
This study will evaluate the safety and effects of the treatment.
Detailed description
The study will consist of 3 phases:
Screening/Baseline Phase: Screening assessments will be conducted within 28 days prior to the eligibility date to determine each patient's overall eligibility and baseline characteristics. These assessments will include medical history, physical examination, Eastern Cooperative Oncology Group (ECOG) performance status (PS), Quality of Life questionnaire, 12 lead electrocardiogram (ECG), echocardiogram (ECHO), vital signs, full hematology and biochemistry, Quality of Life questionnaire, radiologic assessments of baseline disease status and concomitant medications.
For patients with a history of liver surgery or major vasculature surgery, an angiogram evaluation of their vasculature will be performed for compatibility for Percutaneous Hepatic Perfusion (PHP) prior to confirming eligibility.
Eligibility date: This is the date on which all screening assessments have been completed and the patient is determined to be eligible for the trial.
Treatment Phase: The first study treatment should occur within 14 days of the eligibility date. Eligible patients will be treated with Melphalan/HDS 3.0 mg/kg Ideal Body Weight (IBW). Melphalan/HDS treatment will be administered every 6 weeks for a total of 6 cycles with an acceptable delay of another 2 weeks before the next planned treatment to allow for recovery of melphalan-related toxicity, if needed. Tumor response will be assessed every 12 weeks (+ 2 weeks) until disease progression. Patients with progressive disease (PD) will be discontinued from study treatment, and will continue to be followed until death. Melphalan/HDS treatment will also be discontinued if recovery from treatment related toxicity requires more than 8 weeks from the last treatment. An end-of-treatment visit (EOT) will be conducted approximately 6 to 8 weeks following the final study treatment.
Follow-up Phase: Once the patient has completed the end-of-treatment (EOT) visit in accordance with the schedule of events they will enter the follow-up phase. If the disease has not progressed at the EOT, the patient will need to continue with disease assessment visits every 12 weeks (± 2 weeks) until disease progression is documented. After disease progression, follow-up is to be by phone every 3 months for survival status until death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Melphalan/HDS | Experimental | Combination Product: Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS)Eligible patients will be treated with Melphalan/HDS 3.0 mg/kg Ideal Body Weight (IBW). Melphalan/HDS treatment will be administered every 6 weeks for a total of 6 cycles with an acceptable delay of another 2 weeks before the next planned treatment to allow for recovery of melphalan-related toxicity, if needed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female patients ≥ 18 years of age.
- Patients must weigh ≥ 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic Delivery System).
- 50% or less histologically or cytologically-proven ocular melanoma metastases in the parenchyma of the liver.
- Disease in the liver must be measurable by computed tomography (CT) and/or magnetic resonance imaging (MRI).
- Evidence of limited extrahepatic disease on preoperative radiological studies is acceptable if the life-threatening component of disease is in the liver. Limited extrahepatic disease is defined in this protocol as follows: metastasis in bone, subcutaneous, lung or lymph nodes that is amenable to resection or radiation and has a defined treatment plan. Patients with extra-hepatic tumor burden which does not have a defined treatment plan (i.e. monitor or is unable to be resected or radiated) must not be included in the trial.
Key exclusion criteria (23 listed)
- Patients with Child-Pugh Class B or C cirrhosis or with evidence of portal hypertension by history, endoscopy, or radiologic studies.
- Those with New York Heart Association functional classification II, III or IV active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
- History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
- Women of childbearing potential (WOCBP) i.e. fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months) unable to undergo hormonal suppression to avoid menstruation during treatment.
- WOCBP and fertile males (not permanently sterile by bilateral orchiectomy) unwilling or unable to use highly effective contraception method from consent to at least 6 months after the last administration of study treatment (e.g. combined hormonal contraception; progestogen-only hormonal contraception; Intrauterine device, intrauterine hormone-releasing system; bilateral tubal occlusion, vasectomized partner or sexual abstinence).
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 |
|---|---|---|
| Melphalan (3 mg/kg IBW) with Hepatic Delivery System (HDS)Also: percutaneous hepatic perfusion, PHP, HEPZATOMelphalan administered directly to the liver via the Hepatic Delivery System (HDS) infused over a 30 minute period, followed by a 30 minute washout period | Combination product | Melphalan/HDS |
Primary outcome
Adverse Events
Time frame: From eligibility until death due to any cause, for up to 104 weeks
The number and type of adverse events will be assessed per CTCAE version 5.0.
4 secondary outcomes
Efficacy (ORR)
Time frame: Every 12 (+/-2) weeks until progression, for up to 104 weeks
Efficacy (OS)
Time frame: From eligibility until death due to any cause, for up to 104 weeks
Efficacy (PFS)
Time frame: Every 12 (+/-2) weeks until progression, for up to 104 weeks
Quality of Life (FHSI-8)
Time frame: Every 6-8 weeks until the end of treatment, for up to 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 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 (3 mg/kg IBW) with Hepatic Delivery System (HDS) in people with Metastatic Ocular Melanoma and Metastatic Uveal Melanoma, run by Delcath Systems Inc. at 5 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?
The sponsor lists 13 inclusion and 23 exclusion criteria. 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: under way, not looking for participants, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
This study is still under way. Results are not available in the source record yet.
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?
Adverse Events (time frame: From eligibility until death due to any cause, for up to 104 weeks). 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 Dec 2023.