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

Primary Purpose

Liver Metastases

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AvidinOX/ST2210

About this trial

This is an interventional treatment trial for Liver Metastases focused on measuring AvidinOX

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
- 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.
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)
Written informed consent

Exclusion Criteria:

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)
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
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

Sites / Locations

Allgemeines Krankenhaus Wien
Ospedale S. Maria Goretti
Ospedale dell' Angelo di Mestre
S. Andrea Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AvidinOX/ST2210

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Adverse Events

Full Information

NCT ID

NCT02053324

First Posted

January 24, 2014

Last Updated

July 1, 2019

Sponsor

Alfasigma S.p.A.

1. Study Identification

Unique Protocol Identification Number

NCT02053324

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Terminated

Why Stopped

Low recruitment rate

Study Start Date

November 11, 2013 (Actual)

Primary Completion Date

June 1, 2019 (Actual)

Study Completion Date

July 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alfasigma S.p.A.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Primary objectives To identify the Maximum Tolerated Dose (MTD) of 177Lu-ST2210 after prior intra-lesional injection of AvidinOX in the liver. To assess safety and tolerability of intra-lesionally injected AvidinOX + IV injected 177Lu-ST2210 To evaluate intra-lesional distribution and retention of AvidinOX + 177Lu-ST2210 complex in liver metastases To evaluate systemic biodistribution and pharmacokinetics of 177Lu-ST2210 and {AvidinOX + 177Lu-ST2210}- complex Secondary objectives To evaluate proportional 177Lu-ST2210 tumor binding, as a function of total tumor load, and AvidinOX dose injected To demonstrate AvidinOX post-deposition reactivity with 177Lu-ST2210 over time To evaluate whole body dosimetry of IV 177Lu-ST2210 after prior AvidinOX injection (radiation safety dosimetry) To record individual tumor dosimetry To evaluate preliminary efficacy of {AvidinOX + 177Lu-ST2210}-complex in reducing tumor size To evaluate whole body safety dosimetry and dose linearity of IV administered 177Lu-ST2210 after prior intra-lesional injection of AvidinOX To evaluate pharmacokinetics of ST2210 in plasma and urine

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Metastases

Keywords

AvidinOX

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

3+3 dose escalation design

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AvidinOX/ST2210

Arm Type

Experimental

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

AvidinOX/ST2210

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

up to six weeks

Secondary Outcome Measure Information:

Title

Adverse Events

Time Frame

up to 1 year

Other Pre-specified Outcome Measures:

Title

tumor response

Description

Tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST)

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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: 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. 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) Written informed consent Exclusion Criteria: 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) 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 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

Overall Study Officials: