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Table 1 Schedule of enrolment, interventions, and assessments

From: Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial

Week − 4 until − 1 − 1 0 1 2 3 6 7 9 12 24 Treatment discontinuation/disease progression
History1 X   X    X X   X X X X
Physical examination 2 X   X    X X   X X X X
Viral serology 3 X            
Pregnancy test 4 X   X    X X   X    
Hematology and blood chemistry 5 X   X    X X   X X X X
ECG X            
Imaging 6 X       X    X X X
Ipilimumab/Nivolumab i.v.,
every 3 weeks for 4 courses7
   X    X X   X    
PHP7     X     X     
PBMC and EDTA blood8 X       X    X   X
Biopsy metastasis9 X       X      X
  1. ECG electrocardiogram, i.v. intravenous, Hb hemoglobin, Ht hematocrit, ANC absolute neutrophil count, PT prothrombin time, INR international normalized ratio, APTT activated partial thromboplastin time, LDH lactate dehydrogenase, AST aspartate aminotransferase, ALT alanine aminotransferase, GGT gamma-glutamyl transferase, TSH thyroid-stimulating hormone, fT4 free thyroxine, CRP C-reactive protein, ESR erythrocyte sedimentation rate, RECIST 1.1. Response Evaluation Criteria in Solid Tumors version 1.1, DLT dose limiting toxicity, PBMC peripheral blood mononuclear cell, FFPE formalin-fixed paraffin-embedded
  2. 1Histological confirmation of UM liver metastases
  3. 2Including the assessment of patients’ height, weight, performance status, and vital signs
  4. 3HIV antibody titer, HbsAg determination, Anti-HCV, anti-CMV antibody titer
  5. 4For female patients of child bearing age only
  6. 5Hematology: Hb, platelet count, absolute neutrophil count, white blood cell diff, hematocrit, PT/INR, APTT. Chemistry: LDH, phosphorus, sodium, potassium, magnesium, chloride, calcium, creatinine, albumin, total protein, AST, ALT, bilirubin (indirect + direct), GGT, alkaline phosphatase, glucose, amylase, lipase, TSH, fT4, cortisol, CRP, ESR
  7. 6CT of the chest and abdomen, and MRI of the liver (if liver metastases are not measurable according to RECIST 1.1 on CT scan) to assess the number and size of metastases. Lesions must be defined according to RECIST version 1.1. Ideally, initial imaging is performed as closely as possible to the first ipilimumab/nivolumab infusion, but never more than 4 weeks apart. Thereafter, patients should be evaluated with CT/MRI scans every 3 months in year 1, every 4 months in years 2 and 3, and every 6 months in years 4 and 5
  8. 7We will first start with four courses of ipilimumab 1 mg/kg and nivolumab 1 mg/kg and two M-PHP-procedures. In case of a safe application according to the criteria described in the cohort/DLT-section, we will continue with 4 courses of ipilimumab 1 mg/kg and nivolumab 3 mg/kg and two M-PHP-procedures.
  9. 8PBMC’s and EDTA blood (for isolation of plasma and thrombocytes) will be taken twice before the start of treatment. Furthermore, PBMC’s will be collected in week 6, and week 12, and in case of tumor relapse/disease progression
  10. 9Liver biopsies will be performed prior to treatment, in week 6 and in case of tumor relapse/disease progression (optional), 3× 14g: 2× frozen, 1× FFPE for additional molecular biological and immunological tests