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131Iodine-Tenatumomab Treatment in Tenascin-C Positive Cancer Patients (Tenatumomab)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02602067
Recruitment Status : Terminated (Uptake of drug into the tumour lesion was negligible)
First Posted : November 11, 2015
Last Update Posted : September 18, 2018
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
sigma-tau i.f.r. S.p.A.

Brief Summary:
Tenatumomab is a Sigma-Tau developed new anti-Tenascin antibody. It is a murine monoclonal antibody directed towards Tenascin-C. By means of this antibody, Tenascin-C expression was studied on a commercial tissue array slides each carrying malignant breast, colorectal, lung, ovarian or B and T cell Non-Hodgkin Limphoma tissue sections. All these cancers type showed positivity to Tenascin-C between the 64% and 13.3%. Consequently, Sigma-tau is exploring the use of the 131I-labeled Tenatumomab for anti-cancer radioimmunotherapy.

Condition or disease Intervention/treatment Phase
Breast Neoplasm Head and Neck Neoplasm Skin Neoplasm Respiratory Tract Neoplasm Urogenital Neoplasm Digestive System Neoplasm Pancreatic Neoplasm Connective and Soft Tissue Neoplasm Lymphoma, Non-Hodgkin Combination Product: 131I-Tenatumomab Phase 1

Detailed Description:

This will be an open-label dose escalation study. The study will be conducted in two steps:

  1. STEP A aims to identify the optimal amount of antibody to convey the specific radio-label activity of radionuclide.
  2. STEP B will be conducted with the amount of antibody chosen in STEP A, and an escalating radio-labeled therapeutic dose response curve will be performed (3.5 to 5.5 GBq) A maximum of 36 evaluable patients suffering from treatment-refractory Tenascin-C positive tumors.

This dose escalation study will be evaluated using descriptive statistics: no sample size calculation was performed

Primary objectives

  1. To identify the Maximum Tolerated Dose (MTD) and assess Safety and Tolerability of i.v. infused 131I-Tenatumomab.
  2. To identify the optimal amount of unlabeled Tenatumomab able to convey 131I- Tenatumomab with the highest Tumor/nonTumor ratio.
  3. To evaluate the whole body Dosimetry (safety dosimetry) and Tumor to normal tissue ratio (T/nT ratio, referred to AUC) of i.v.infused 131I-Tenatumomab.
  4. To evaluate intra-lesional distribution and retention of 131I-Tenatumomab and to record individual lesion dosimetry.
  5. To evaluate systemic biodistribution, pharmacokinetics, urinary excretion and dose linearity of 131I-Tenatumomab.

Secondary objectives

  1. To evaluate proportional 131I-Tenatumomab tumor binding, as a function of the total load.
  2. To evaluate Pharmacokinetics of Tenatumomab (protein and protein related materials) in serum.
  3. To evaluate preliminary Efficacy of 131I-Tenatumomab based on disease response rate (Complete Response, Partial Response, Stable Disease) and patient's general clinical condition by ECOG performance status assessment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Tenatumomab infusion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dose Escalation Study to Evaluate Safety, Tolerability Dosimetry, Pharmacokinetics and Preliminary Efficacy of 131I-Tenatumomab Treatment in Tenascin-C Positive Cancer Patients
Study Start Date : November 2015
Actual Primary Completion Date : April 30, 2017
Actual Study Completion Date : April 30, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 131I-Tenatumomab

Diagnostic: each patient will receive one single i.v. infusion of 370 MBq±10% 131I-Tenatumomab in 10 ml of saline (conveyed by 10 ±10%, 20 ±10%, 40 ±10% mg of Tenatumomab). It will be administered as a short infusion in approximately 30 minutes (333 ° µl / min).

Therapeutic: each patient will receive one single i.v. infusion, escalating 131I-Tenatumomab dose starting at 2.5 GBq±10%,with escalation steps of 1 GBq, up to 5.5 GBq±10% in 10 ml of saline, (conveyed by 10 ±10% , 20 ±10%, 40 ±10% mg of Tenatumomab). It will be administered as a short infusion in approximately 30 minutes (333° µl / min)

Combination Product: 131I-Tenatumomab
I131anti-Tenascin monoclonal antibody administered to be targeted on neoplasms expressing Tenascin-C
Other Name: Tenatumomab/ST2146




Primary Outcome Measures :
  1. Dose Limiting Toxicity evaluated using NCI Common Toxicity Criteria (CTCAE 4.03) [ Time Frame: up to six weeks ]
    no more details necessary


Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: up to 1 year ]
    no more details necessary


Other Outcome Measures:
  1. Tumor response [ Time Frame: 1 year ]
    Tumor response according to Response Evaluation Criteria in Solid Tumors RECIST V 1.1 or PERCIST



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Written informed consent.
  • 2. A patient who has (a) a histologically documented advanced tumor that has relapsed from, or is refractory to, standard treatment and for which no other standard treatment is available and (b) confirmed Tenascin-C expression obtained through a biopsy on at least one reachable tumor lesion.

These patients will have failed one or more prior therapeutic line and had assessable and measurable disease expression, but were not considered eligible for other standard approaches with curative intent, as assessed by the Investigator.

  • 3. Agreement to hemopoietic stem cell collection procedures (the procedure will be performed upon clinical evaluation of the Investigator and if deemed necessary in the interest of the patient).
  • 4. Male or female ≥18 years of age
  • 5. Eastern Cooperative Oncology Group (ECOG), or WHO performance status of ≤ 2 or Karnofsky > 60
  • 6. Life expectancy of at least 3 months.
  • 7. Negative pregnancy test for all women of child-bearing potential. Appropriate contraception (one highly effective method or a combination of acceptable methods) is to be used during the study period and until 90 days after the last follow-up visit (End of Study Visit)
  • 8. Hematological, thyroid, liver, cardiac and renal function test results ≤ grade 2 toxicity (according to US National Cancer Institute's "Common Terminology Criteria for Adverse Events v4.03 [CTCAE]"), e.g.:

Haematology:

  • Hematocrit ≥ 30%
  • Hemoglobin ≥ 9.0 g/dl
  • White blood cell count ≥ 3 x 109/L
  • Neutrophils > 1.5 x109/L
  • Platelets ≥ 100x 109/L

Thyroid:

- Free-Triiodothyronine and Free-Thyroxine ≤ 3 times upper limit of normal or >3 times lower limit of normal.

Liver:

  • Alanine transaminase, Aspartate transaminase, Alkaline Phosphatase ≤ 2.5 times institutional upper limit of normal (ULN) or ≤5 x ULN in presence of liver metastases.
  • Bilirubin ≤ 1.5 x ULN or ≤3 x ULN in presence of liver metastases.

Renal:

  • Urine protein: ≤30 mg/dl or dipstick: ≤3
  • eGFR≥60 ml/min/1.73 m2 (with Chronic kideny disease-Epidemiology collaboration formula)

Cardiac

• Resting Ejection Fraction (EF) ≥ 50%

Exclusion Criteria:

  • 1. Known hypersensitivity to Tenatumomab, Iodine or any excipient.
  • 2. Active infection at screening or history of severe infection within the previous 2 months, if considered clinically relevant by the Investigator.
  • 3. Positive test to Human Immunodeficiency Virus (HIV) and/or chronically active Hepatitis B or C.
  • 4. Patients with primary Central nervous system tumor or cerebral metastases.
  • 5. Administration of another investigational medicinal product within 45days before the screening period.
  • 6. Previous treatment with any radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide used prior to the administration of study drug.
  • 7. History of somatic or psychiatric disease/condition that may interfere with the objectives of the study.
  • 8. Major illness, trauma, or surgery within 2 weeks before the screening period, if considered clinically significant by the Investigator.
  • 9. Patient who underwent chemotherapy and/or radiation therapy and/or treatments with biologics (which are not to be of murine origin) within 4 weeks before the screening period.
  • 10. Women who are breast feeding, due to the potential risk of damage to the infant.
  • 11. Men unwilling to use appropriate contraceptive methods during the study and up to 90 days after the last follow-up visit (End of Study Visit).
  • 12. Bladder catheterization cannot be performed, or the patient is unwilling to be catheterized if necessary.
  • 13. Murine antibodies treated patients. It is at the discretion of the Investigator to exclude patients who have worsened considerably from screening to Day -1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02602067


Locations
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France
Institut Bergonnie
Bordeaux, France, 33076
Centre Leon Berard
Lyon, France, 69373
Icm Val D'Aurelle
Montpellier, France, 34298
Italy
Istituto Nazionale Dei Tumori Irccs - Fondazione "G. Pascale"
Naples, Italy, 80131
University of Study of Pisa
Pisa, Italy, 65126
S. Maria Nuova Hospital - Irccs
Reggio Emilia, Italy, 42123
Humanitas Clinical Institute
Rozzano Mi, Italy, 20089
Sponsors and Collaborators
sigma-tau i.f.r. S.p.A.
Medpace, Inc.
Investigators
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Study Chair: SECONDO LASTORIA, M.D. ISTITUTO NAZIONALE DEI TUMORI IRCCS - FONDAZIONE "G. PASCALE" NAPLES - ITALY
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Responsible Party: sigma-tau i.f.r. S.p.A.
ClinicalTrials.gov Identifier: NCT02602067    
Other Study ID Numbers: TENATUMOMAB/ST2146-CR-14-001
2014-003832-38 ( EudraCT Number )
First Posted: November 11, 2015    Key Record Dates
Last Update Posted: September 18, 2018
Last Verified: January 2018
Additional relevant MeSH terms:
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Neoplasms
Breast Neoplasms
Lymphoma, Non-Hodgkin
Head and Neck Neoplasms
Pancreatic Neoplasms
Digestive System Neoplasms
Gastrointestinal Neoplasms
Urogenital Neoplasms
Skin Neoplasms
Respiratory Tract Neoplasms
Soft Tissue Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Site
Breast Diseases
Skin Diseases
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gastrointestinal Diseases
Thoracic Neoplasms
Respiratory Tract Diseases