TheranosticTrials.org

Clinical Trial · NCT02053324

AvidinOX + [177Lu]DOTA-biotin (or 177Lu-ST2210) Complex in Patients With Liver Metastases From Colorectal Cancer

Overview

The purpose of the study is to assess a new treatment for patients with liver tumor metastases from colorectal cancer. The treatment has never been used in humans before. The treatment foresees the use of two compounds: AvdinOX and \[177Lu\]DOTA-biotin. AvidinOX is a new compound, essentially a natural protein obtained from hen eggs, while \[177Lu\]DOTA-biotin is a new chemical compound resulting from the combination of the DOTA-biotin (also deriving from a natural vitamin which is biotin) with the 177Lutetium, an atom which emits radiation. AvidinOX will be injected directly into the metastases in the liver and \[177Lu\]DOTA-biotin will be injected into the arm vein. One specific property of AvidinOX is that it chemically links to the tumor tissues when it is injected while maintaining the capacity to take up \[177Lu\]DOTA-biotin. Once locally bound in tumor tissue, AvidinOX becomes an "artificial receptor" for intravenously injected \[177Lu\]DOTA-biotin, which allows an internal radiation therapy of the tumor tissue. The treatment of liver metastases with local injection of AvidinOX and the following intra-venous injection of \[177Lu\]DOTA-biotin could be simpler and more tolerable than the current available treatments.

Sponsor

Unknown Organization

Phase

Phase 1

Contacts

Alexander Haug, MD (PRINCIPAL_INVESTIGATOR)

Andreas Wicki, MD (PRINCIPAL_INVESTIGATOR)

Roberto Cianni, MD (PRINCIPAL_INVESTIGATOR)

Francesco Scopinaro, MD (PRINCIPAL_INVESTIGATOR)

Michele Sicolo, MD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT02053324

Drug / Compound

ST2210

Isotope(s):
Target(s):
  • Biotin
Ligand Class: Small Molecules
Chelator: DOTA

Eligibility

Inclusion

  • Activated Partial Thromboplastin Time (aPTT). Patients showing an increase of the ULN of about 20% can also be considered for inclusion
  • Life expectancy of at least 3 months.
  • Urine protein dipstick: 0
  • Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP) ≤ 5 times upper limit of normal
  • Liver metastases from histologically confirmed colorectal cancer and at least one liver metastasis ≥ 1 cm (measurable disease), which is chemo-resistant, not eligible for curative surgery and suitable for intra-lesional injection as assessed by the investigator.
  • Fibrinogen. Patients showing a decrease of the Lower Limit of the Normal range (LLN) of about 20% can also be considered for inclusion.
  • Platelets ≥ 80x 109/L
  • Bilirubin ≤ 3 times upper limit of normal
  • Haemoglobin ≥ 8 g/dl
  • Haematology:
  • estimated Glomerular Filtration Rate (eGFR)\> 30 ml/min/1.73 m2 (with CKD-EPI formula)
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Haematological, liver and renal function test results ≤ grade 2 toxicity (according to US National Cancer Institute's "Common Terminology Criteria for Adverse Events v4.03 \[CTCAE\]"), i.e.:
  • Prothrombin Time (Quick).Patients showing an increase of the Upper Limit of the Normal (ULN) range of about 20% can also be considered for inclusion.
  • Maximum of 9 liver metastases
  • Total liver tumor burden requiring ≤ 75 ml AvidinOX
  • International Normalised Ratio (INR). Patients showing an increase of the ULN of about 20% can also be considered for inclusion
  • Clotting parameters as follows, with local normal ranges to be taken as reference:
  • Liver:
  • White blood cell count ≥ 2 x 109/L
  • Renal:

Exclusion

  • Known hypersensitivity to Avidin or AvidinOX (e.g. hen egg)
  • Men unwilling to use appropriate contraceptive methods during the study and up to six months after the end of the study
  • Previous treatment with Selective Internal Radiation Therapy (SIRT) spheres or any radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide used for labeling the respective radiopharmaceutical prior to the administration of study drug.
  • Inability or unwillingness to be catheterized
  • Women of child-bearing potential. A permanent postmenopausal status must be proven as follows: history of hysterectomy or hormone analysis in serum: estradiol \< 20 pg/ml and follicle stimulating hormone (FSH) \> 40 IU/L, or amenorrhea starting at least 1 year prior to the study start andnegativeβHCG .
  • History of somatic or psychiatric disease/condition that may interfere with the objectives of the study
  • Known human immunodeficiency virus (HIV) positive serology or chronically active hepatitis B or C.
  • Patient who underwent chemotherapy, radiation therapy within 15 days before the screening period
  • Active infection at screening or history of severe infection within the previous 3 months, if clinically relevant at screening as considered by the investigator
  • Administration of another investigational medicinal product within 30 days before the screening period.
  • Life limiting metastases outside the liver. Metastases outside the liver are allowed only in case the residual metastases (after liver treatment) are amenable to further treatments (e.g. surgical removal)
  • Known hypersensitivity to ST2210(DOTA biotin) or any excipient.
  • Clinically significant illness or clinically relevant trauma within 15 days before the screening period
  • Presence of unreachable (e.g. located in a region in the liver that cannot be reached by needle, or too close to major blood vessels or adjacent to main organs) or untreatable hepatic lesions so that the benefit from the treatment of the treatable lesions does not justify patient's inclusion