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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
I131anti-Tenascin monoclonal antibody administered to be targeted on neoplasms expressing Tenascin-C
Institut Bergonnie
Bordeaux, France
Centre Leon Berard
Lyon, France
Icm Val D'Aurelle
Montpellier, France
Istituto Nazionale Dei Tumori Irccs - Fondazione "G. Pascale"
Naples, Italy
University of Study of Pisa
Pisa, Italy
S. Maria Nuova Hospital - Irccs
Reggio Emilia, Italy
Humanitas Clinical Institute
Rozzano MI, Italy
Dose Limiting Toxicity evaluated using NCI Common Toxicity Criteria (CTCAE 4.03)
no more details necessary
Time frame: up to six weeks
Adverse Events
no more details necessary
Time frame: up to 1 year
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