Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases

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Brief Title

Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases

Official Title

SCANDIUM II Trial - A Phase I Randomized Controlled Multicentre Trial of Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases

Brief Summary

      Uveal melanoma is the most common primary intraocular malignancy in adults. Despite
      successful control of the primary tumour, 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. Isolated hepatic perfusion
      is a regional treatment where the liver is completely isolated from the systemic circulation,
      allowing a high concentration of chemotherapy to be perfused through the liver with minimal
      systemic exposure. The introduction of modern immunotherapy in the treatment arsenal for
      cutaneous melanoma also creates hope for patients with uveal melanoma metastases. However,
      the results of immunotherapy have so far been disappointing. The reason for the low efficacy
      could be that uveal melanoma develops in the immune privileged eye.

      The hypothesis in this trial is that isolated hepatic perfusion with melphalan causes an
      immunogenic type of cell death by local tumour destruction while leaving the immune-system
      intact. This will cause an activation of the immune-system and the addition of ipilimumab and
      nivolumab will enhance this effect, ultimately increasing the treatment efficacy.

      The primary objective of this trial is to evaluate the safety and tolerability of isolated
      hepatic perfusion together with ipilimumab and nivolumab when given at the same time or as a
      sequenced regimen. The study design is a phase I randomized controlled, multicentre,
      open-label trial. Active follow-up will be performed for 2 years. Patients will be randomized
      after diagnoses of metastatic disease to one of the following treatment arms:

      Arm A. Patients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and
      nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.

      Arm B. Patients will be treated with 1 course of ipilimumab 3mg/kg and nivolumab 1mg/kg
      followed by IHP after 3 weeks and then another 3 courses of ipilimumab 3mg/kg and nivolumab
      1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome

 Objective response rate (ORR)

Condition

Uveal Melanoma

Intervention

Isolated hepatic perfusion

Study Arms / Comparison Groups

 Arm A
Description:  Patients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

18

Start Date

March 8, 2021

Completion Date

June 1, 2023

Primary Completion Date

June 1, 2022

Eligibility Criteria

        Inclusion Criteria

          1. Patient is ≥18 years of age on the day of signing informed consent

          2. Patient is willing and able to provide written informed consent and comply with study
             procedures. Written informed consent must be signed and dated before the start of
             specific protocol procedures

          3. Patient must have a histologically confirmed diagnosis of stage IV uveal melanoma. If
             tissue biopsy is judged not feasible by the investigator, cytological diagnosis from
             fine needle aspiration (FNA) will be accepted

          4. Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per
             RECIST 1.1 criteria with at least one target lesion identified in the liver.

          5. ECOG performance status of 0 or 1

          6. No previous immunotherapy for uveal melanoma metastases.

          7. 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

          8. Female patients of childbearing potential must be willing to use an adequate method of
             contraception, for the course of the study through 120 days after the last dose of
             study medication. Note: Abstinence is acceptable if this is the usual lifestyle and
             preferred contraception for the subject

          9. Male patients of childbearing potential must agree to use an adequate method of
             contraception, starting with the first dose of study therapy through 120 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 3 months

          2. Body mass index above 35

          3. More than 50% of the liver volume replaced by tumor as measured by CT or MRI

          4. Known congestive heart failure with an LVEF <40%

          5. COPD or other chronic pulmonary disease with PFT's indicating an FEV< 50% predicted
             for age

          6. Interstitial lung disease (ILD) or (non-infectious) pneumonitis

          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>3*ULN and PK-INR>1.5) or
             medical history of liver cirrhosis or portal hypertension

          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 hypersensitivity reactions to mAbs

         12. Known human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome
             (AIDS), hepatitis B or hepatitis C

         13. Active autoimmune disease or a history of known or suspected autoimmune disease

         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 120 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

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, +46 31 3428207, [email protected]

Location Countries

Sweden

Location Countries

Sweden

Administrative Informations


NCT ID

NCT04463368

Organization ID

CA184-587


Responsible Party

Principal Investigator

Study Sponsor

Sahlgrenska University Hospital, Sweden

Collaborators

 Bristol-Myers Squibb

Study Sponsor

, , 


Verification Date

March 2021