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

NCT02053324 | Terminated Phase 1 DMC

• 2 other identifiers: AvOX/ST2210-CR-12-0012012-005577-32
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

Liver Metastases

Keywords

AvidinOX

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity evaluated using NCI Common Toxicity Criteria (CTCAE 4.03)

  up to six weeks

Secondary Outcomes (1)

• Adverse Events

  up to 1 year

Other Outcomes (1)

• tumor response

  1 year

Study Arms (1)

AvidinOX/ST2210

EXPERIMENTAL

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 15 % of the lesion volume followed by intravenous infusion of 177Lu-ST2210 Diagnostic dose : 10 ml, 250 MBq±10%177Lu, approximately 1 mg ST2210, 100 mg/mL ascorbic acid, followed by intravenous infusion 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

Combination Product: AvidinOX/ST2210

Interventions

AvidinOX/ST2210 COMBINATION_PRODUCT

One intralesion injection of AvidinOX followed by an intravenous infusion of ST2210

AvidinOX/ST2210

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Known hypersensitivity to Avidin or AvidinOX (e.g. hen egg)
• Known hypersensitivity to ST2210(DOTA biotin) or any excipient.
• 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)
• Active infection at screening or history of severe infection within the previous 3 months, if clinically relevant at screening as considered by the investigator
• Known human immunodeficiency virus (HIV) positive serology or chronically active hepatitis B or C.
• Administration of another investigational medicinal product within 30 days before the screening period.
• 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.
• 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 .
• Men unwilling to use appropriate contraceptive methods during the study and up to six months after the end of the study
• Inability or unwillingness to be catheterized
• History of somatic or psychiatric disease/condition that may interfere with the objectives of the study
• Clinically significant illness or clinically relevant trauma within 15 days before the screening period
• Patient who underwent chemotherapy, radiation therapy within 15 days before the screening period

Sponsors & Collaborators

• Alfasigma S.p.A.: lead

Study Sites (4)

Allgemeines Krankenhaus Wien

Vienna, 1090, Austria

Location

Ospedale S. Maria Goretti

Latina, ROME, 04100, Italy

Location

Ospedale dell' Angelo di Mestre

Mestre, Venice, 30174, Italy

Location

S. Andrea Hospital

Rome, 00189, Italy

Location

Related Publications (4)

• Vesci L, Carollo V, Rosi A, De Santis R. Therapeutic efficacy of intra-tumor AvidinOX and low systemic dose biotinylated cetuximab, with and without cisplatin, in an orthotopic model of head and neck cancer. Oncol Lett. 2019 Mar;17(3):3529-3536. doi: 10.3892/ol.2019.10003. Epub 2019 Feb 1.

  PMID: 30867794 DERIVED

• Milazzo FM, Anastasi AM, Chiapparino C, Rosi A, Leoni B, Vesci L, Petronzelli F, De Santis R. AvidinOX-anchored biotinylated trastuzumab and pertuzumab induce down-modulation of ErbB2 and tumor cell death at concentrations order of magnitude lower than not-anchored antibodies. Oncotarget. 2017 Apr 4;8(14):22590-22605. doi: 10.18632/oncotarget.15145.

  PMID: 28186982 DERIVED

• Vesci L, Milazzo FM, Anastasi AM, Petronzelli F, Chiapparino C, Carollo V, Roscilli G, Marra E, Luberto L, Aurisicchio L, Pacello ML, Spagnoli LG, De Santis R. Intra-tumor AvidinOX allows efficacy of low dose systemic biotinylated Cetuximab in a model of head and neck cancer. Oncotarget. 2016 Jan 5;7(1):914-28. doi: 10.18632/oncotarget.6089.

  PMID: 26575422 DERIVED

• Albertoni C, Leoni B, Rosi A, D'Alessio V, Carollo V, Spagnoli LG, van Echteld C, De Santis R. Radionuclide Therapy of Unresectable Tumors with AvidinOX and (90)Y-biotinDOTA: Tongue Cancer Paradigm. Cancer Biother Radiopharm. 2015 Sep;30(7):291-8. doi: 10.1089/cbr.2015.1837. Epub 2015 Jul 13.

  PMID: 26167947 DERIVED

Study Officials

• Alexander Haug, 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)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation design

Study Record Dates

• First Submitted: January 24, 2014
• First Posted: February 3, 2014
• Study Start: November 11, 2013
• Primary Completion: June 1, 2019
• Study Completion: July 1, 2019
• Last Updated: July 5, 2019

Record last verified: 2019-07

Locations

IT (3); AU (1)