Trial Title:
PHP in Combination With IPI1/NIVO3 Compared to IPI3/NIVO1 Only in Patients With Uveal Melanoma Liver Metastases
NCT ID:
NCT06519266
Condition:
Uveal Melanoma
Liver Metastases
Conditions: Official terms:
Melanoma
Neoplasm Metastasis
Liver Neoplasms
Uveal Neoplasms
Nivolumab
Ipilimumab
Melphalan
Conditions: Keywords:
Percutaneous Hepatic Perfusion
Immunotherapy
Uveal Melanoma
Liver metastases
SCANDIUM III trial
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Device
Intervention name:
PHP
Description:
Patients will be treated with 2 cycles of PHP (CHEMOSAT® Hepatic Delivery System for
Melphalan) six weeks apart
Arm group label:
PHP + IPI1/NIVO3
Other name:
CHEMOSAT® Hepatic Delivery System for Melphalan
Intervention type:
Drug
Intervention name:
IPI1/NIVO3
Description:
Patients will be treated with 2 cycles of i.v. ipilimumab 1mg/kg and nivolumab 3mg/kg
q3w, followed by continued i.v. nivolumab 480mg q4w up to 1 year.
Arm group label:
PHP + IPI1/NIVO3
Other name:
Ipilimumab 1 mg/kg
Other name:
Nivolumab 3 mg/kg
Intervention type:
Drug
Intervention name:
IPI3/NIVO1
Description:
Patients will be treated with 4 cycles of intravenous (i.v.) infusion with ipilimumab
3mg/kg and nivolumab 1mg/kg q3w followed by continued i.v. nivolumab 480mg q4w up to 1
year.
Arm group label:
IPI3/NIVO1
Other name:
Ipilimumab 3 mg/kg
Other name:
Nivolumab 1 mg/kg
Summary:
Uveal melanoma is the most common primary intraocular malignancy in adults. Despite
successful control of the primary tumor, metastatic disease will develop in approximately
35%-50% of the patients within 10 years. The liver is the most common site for
metastases, and about 50% of the patients will have isolated liver metastases. These
metastases are generally refractory to systemic chemotherapy and the median survival for
patients with liver metastases is about 6 months. Regardless of treatment, the mortality
rate is approximately 90% at 2 years with only about 1% of the patients surviving more
than 5 years.
The primary objective with this study is to evaluate progression-free survival in
patients with uveal melanoma liver metastases randomized to either percutaneous hepatic
perfusion (PHP) in combination with ipilimumab and nivolumab or ipilimumab and nivolumab
only. Secondary objectives include further efficacy and safety analysis, as well as
biomarker discovery.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patient is ≥18 years.
2. Signed informed consent.
3. ECOG performance status of 0 or 1.
4. Histologically or cytologically confirmed liver metastasis of uveal melanoma.
5. Measurable disease by computed tomography (CT) per RECIST 1.1 criteria with at least
one target lesion identified in the liver.
6. No previous treatment for uveal melanoma metastases, except patients that have
confirmed progression on tebentafusp, or after surgical resection or ablative
treatments (e.g., radiofrequency ablation or stereotactic body radiation therapy).
7. Patient deemed suitable for percutaneous hepatic perfusion.
8. Female patient of childbearing potential should have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first treatment. If the urine
test is positive or cannot be confirmed as negative, a serum pregnancy test will be
required.
9. Female patients of childbearing potential must be willing to use an adequate method
of contraception, for the course of the study through 150 days after the last dose
of study medication. Note: Abstinence is acceptable if this is the usual lifestyle
and preferred contraception for the subject.
10. Male patients of childbearing potential must agree to use an adequate method of
contraception, starting with the first dose of study therapy through 150 days after
the last dose of study therapy. Abstinence is acceptable if this is the usual
lifestyle and preferred contraception for the subject.
Exclusion Criteria:
1. Life expectancy of less than 6 months.
2. More than 50% of the liver volume replaced by tumor as measured by CT.
3. Extrahepatic disease as measured by CT of thorax and abdomen.
4. History of congestive heart failure, active cardiac conditions, including unstable
coronary syndromes (unstable or severe angina, recent myocardial infarction),
significant arrhythmias and severe valvular disease that precludes the use of
general anesthesia.
5. History or evidence of clinically significant pulmonary disease e.g. severe COPD
that precludes the use of general anesthesia.
6. Patients who are unable to undergo general anesthesia for any reason.
7. Reduced renal function defined as S-Creatinine >=1.5xULN or Creatinine Clearance <
40 mL/min, calculated using the Cockroft and Gault formula.
8. Reduced hepatic function (defined as AST, ALT, bilirubin>2.5*ULN and PK-INR>1.5) or
medical history of liver cirrhosis (Child-Pugh Class B or C) or evidence of portal
hypertension by history, endoscopy or radiology.
9. Hemoglobin <90 g/L or platelets <100x109/L or neutrophils <1.5x109/L.
10. Use of live vaccines four weeks before or after the last study treatment.
11. History of severe reactions to monoclonal antibodies, melphalan, heparin or iodine
contrast.
12. Known human immunodeficiency virus (HIV) infection, acquired immunodeficiency
syndrome (AIDS), hepatitis B or hepatitis C.
13. Active autoimmune disease or a documented history of autoimmune disease requiring
systemic immunomodulatory treatment. Diabetes, rheumatoid arthritis, psoriasis,
atopic dermatitis and hypothyroidism are excepted.
14. A condition requiring systemic treatment with either corticosteroids (>10 mg daily
prednisone equivalents) or other immunosuppressive medications within 14 days of
study drug administration. Inhaled or topical steroids and adrenal replacement doses
>10 mg daily prednisone equivalents are permitted in the absence of active
autoimmune disease.
15. Concomitant therapy with any other anti-cancer therapy, concurrent medical
conditions requiring use of immunosuppressive medications or use of other
investigational drugs.
16. Has a known additional malignancy that is progressing or requires active treatment.
17. Pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 150 days
after the last dose of study drug.
18. A history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the patient's
participation for the full duration of the study, or is not in the best interest of
the patient to participate in the opinion of the treating investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sahlgrenska University Hospital
Address:
City:
Gothenburg
Country:
Sweden
Contact:
Last name:
Lars Ny, MD, PhD
Investigator:
Last name:
Lars Ny, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Linköping University Hospital
Address:
City:
Linköping
Country:
Sweden
Contact:
Last name:
Sander Ellegård, MD, PhD
Investigator:
Last name:
Sander Ellegård, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Skåne University Hospital
Address:
City:
Lund
Country:
Sweden
Contact:
Last name:
Ana Carneiro, MD, PhD
Investigator:
Last name:
Ana Carneiro, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Karolinska University Hospital,
Address:
City:
Stockholm
Country:
Sweden
Contact:
Last name:
Hildur Helgadottir, MD, PhD
Investigator:
Last name:
Hildur Helgadottir, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Norrland University Hospital
Address:
City:
Umeå
Country:
Sweden
Contact:
Last name:
Sara Wirén, MD, PhD
Investigator:
Last name:
Sara Wirén, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Uppsala University Hospital
Address:
City:
Uppsala
Country:
Sweden
Start date:
August 1, 2024
Completion date:
December 31, 2030
Lead sponsor:
Agency:
Vastra Gotaland Region
Agency class:
Other
Source:
Vastra Gotaland Region
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06519266
