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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by sigma-tau i.f.r. S.p.A.
Sponsor:
Information provided by (Responsible Party):
sigma-tau i.f.r. S.p.A.
ClinicalTrials.gov Identifier:
NCT02053324
First received: January 24, 2014
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Liver Metastases
Radiation: AvidinOX/ST2210
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Dosimetry, Maximum Tolerated Dose and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by Systemic IV Administration of Escalating Doses of [177Lu]DOTA-biotin in Patients With Liver Metastases From Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by sigma-tau i.f.r. S.p.A.:

Primary Outcome Measures:
  • Dose Limiting Toxicity evaluated using NCI Common Toxicity Criteria (CTCAE 4.03) [ Time Frame: up to six weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adverse Events [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • tumor response [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST)


Estimated Enrollment: 30
Study Start Date: September 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AvidinOX/ST2210
AvidinOX/ST2210 - vial containing 22.5 mg AvidinOX + vials containing 10 ml of water for injection (WFI) for the reconstitution in a clear solution with an AvidinOX concentration of 3 mg/ml. One Intralesion administration of a volume of reconstituted AvidinOX equal to 10 % of the lesion volume followed by intravenous injection of 177Lu-ST2210 Diagnostic dose : 10 ml, 250 MBq±10%177Lu, approximately 1 mg ST2210, 100 mg/mL ascorbic acid, followed by intravenous injection of a therapeutic dose: 25 ml, escalating 177Lu dose starting at 5 Gigabequerel (GBq) ±10%with escalation steps of 2.5 GBq up to 15 GBq ±10%, approximately 1 mg ST2210, 100 mg/ml ascorbic acid
Radiation: AvidinOX/ST2210
One intralesion injection of AvidinOX followed by an intravenous infusion of ST2210

Detailed Description:

Primary objectives

  1. To identify the Maximum Tolerated Dose (MTD) of 177Lu-ST2210 after prior intra-lesional injection of AvidinOX in the liver.
  2. To assess safety and tolerability of intra-lesionally injected AvidinOX + IV injected 177Lu-ST2210
  3. To evaluate intra-lesional distribution and retention of AvidinOX + 177Lu-ST2210 complex in liver metastases
  4. To evaluate systemic biodistribution and pharmacokinetics of 177Lu-ST2210 and {AvidinOX + 177Lu-ST2210}- complex

Secondary objectives

  1. To evaluate proportional 177Lu-ST2210 tumor binding, as a function of total tumor load, and AvidinOX dose injected
  2. To demonstrate AvidinOX post-deposition reactivity with 177Lu-ST2210 over time
  3. To evaluate whole body dosimetry of IV 177Lu-ST2210 after prior AvidinOX injection (radiation safety dosimetry)
  4. To record individual tumor dosimetry
  5. To evaluate preliminary efficacy of {AvidinOX + 177Lu-ST2210}-complex in reducing tumor size
  6. To evaluate whole body safety dosimetry and dose linearity of IV administered 177Lu-ST2210 after prior intra-lesional injection of AvidinOX
  7. To evaluate pharmacokinetics of ST2210 in plasma and urine
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female ≥ 18 years of age
  2. 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.
  3. Total liver tumor burden requiring ≤ 75 ml AvidinOX
  4. Maximum of 9 liver metastases
  5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  6. Life expectancy of at least 3 months.
  7. Clotting parameters as follows, with local normal ranges to be taken as reference:

    • 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.
    • International Normalised Ratio (INR). Patients showing an increase of the ULN of about 20% can also be considered for inclusion
    • Activated Partial Thromboplastin Time (aPTT). Patients showing an increase of the ULN of about 20% can also be considered for inclusion
    • Fibrinogen. Patients showing a decrease of the Lower Limit of the Normal range (LLN) of about 20% can also be considered for inclusion.
  8. 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.:

    • Haematology:

      • Haemoglobin ≥ 8 g/dl
      • White blood cell count ≥ 2 x 109/L
      • Platelets ≥ 80x 109/L
    • Liver:

      • Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP) ≤ 5 times upper limit of normal
      • Bilirubin ≤ 3 times upper limit of normal
    • Renal:

      • Urine protein dipstick: 0
      • estimated Glomerular Filtration Rate (eGFR)> 30 ml/min/1.73 m2 (with CKD-EPI formula)
  9. Written informed consent

Exclusion Criteria:

  1. Known hypersensitivity to Avidin or AvidinOX (e.g. hen egg)
  2. Known hypersensitivity to ST2210(DOTA biotin) or any excipient.
  3. 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)
  4. 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
  5. Active infection at screening or history of severe infection within the previous 3 months, if clinically relevant at screening as considered by the investigator
  6. Known human immunodeficiency virus (HIV) positive serology or chronically active hepatitis B or C.
  7. Administration of another investigational medicinal product within 30 days before the screening period.
  8. 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.
  9. 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 .
  10. Men unwilling to use appropriate contraceptive methods during the study and up to six months after the end of the study
  11. Inability or unwillingness to be catheterized
  12. History of somatic or psychiatric disease/condition that may interfere with the objectives of the study
  13. Clinically significant illness or clinically relevant trauma within 15 days before the screening period
  14. Patient who underwent chemotherapy, radiation therapy within 15 days before the screening period
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02053324

Contacts
Contact: CAMERINI ROBERTO, M.D. +39-06-91391 ext 3562 roberto.camerini@sigma-tau.it

Locations
Austria
Allgemeines Krankenhaus Wien Recruiting
Wien, Austria, 1090
Contact: HOFFMANN MARTHA, M.D.    +43 1 40400 ext 5550    martha.hoffmann@meduniwien.ac.at   
Principal Investigator: HOFFMANN MARTHA, M.D.         
Italy
Ospedale S. Maria Goretti Not yet recruiting
Latina, Rome, Italy, 04100
Contact: CIANNI ROBERTO, M.D.    +39 0773 655 3659    r.cianni@ausl.latina.it   
Principal Investigator: CIANNI ROBERTO, M.D.         
Ospedale dell' Angelo di Mestre Not yet recruiting
Mestre, Venice, Italy, 30174
Contact: SICOLO MICHELE, M.D.    +39 041 965 7626 ext 7629    michele.sicolo@ulss12.ve.it   
Principal Investigator: SICOLO MICHELE, M.D.         
S. Andrea Hospital Not yet recruiting
Rome, Italy, 00189
Contact: SCOPINARO FRANCESCO, M.D.    +39 06 337 75538    francesco.scopinaro@uniroma1.it   
Principal Investigator: SCOPINARO FRANCESCO, M.D.         
Switzerland
Universtitätsspital Basel Not yet recruiting
Basel, Switzerland, 4031
Contact: WICKI ANDREAS, M.D.    +41 61 265-5074    awicki@uhbs.ch   
Principal Investigator: WICKI ANDREAS, M.D.         
Sponsors and Collaborators
sigma-tau i.f.r. S.p.A.
Investigators
Principal Investigator: Martha Hoffmann, MD Allgemeines Krankenhaus Wien (Austria)
Principal Investigator: Andreas Wicki, MD Universitatsspital Basel (Switzerland)
Principal Investigator: Francesco Scopinaro, MD St. Andrea Hospital Rome (Italy)
Principal Investigator: Roberto Cianni, MD S Maria Goretti Hospital - Latina (Italy)
Principal Investigator: Michele Sicolo, MD Dell'Angelo Hospital - Mestre (Italy)
  More Information

No publications provided

Responsible Party: sigma-tau i.f.r. S.p.A.
ClinicalTrials.gov Identifier: NCT02053324     History of Changes
Other Study ID Numbers: AvOX/ST2210-CR-12-001, 2012-005577-32
Study First Received: January 24, 2014
Last Updated: January 31, 2014
Health Authority: Austria: Agency for Health and Food Safety
Italy: The Italian Medicines Agency
Switzerland: Swissmedic

Keywords provided by sigma-tau i.f.r. S.p.A.:
AvidinOX

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases

ClinicalTrials.gov processed this record on September 18, 2014