Pharmacokinetic Profile of T-ChOS™ in Subjects With Advanced Solid Tumors (CHITIN)

Study Overview
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Brief Summary
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This is a single center phase 1 trial, which evaluates the pharmacokinetic profile of T-ChOS™ (food supplement Benecta™) in subjects with advanced solid tumors.

Detailed Description
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YKL-40 (also named chitinase 3 like-1 protein, CHI3L1), is a member of the mammalian chitinase like proteins and is a highly conserved glycoprotein. YKL-40 is produced by cancer cells and macrophages and promotes cancer progression by activating inflammation and inhibiting tumor angiogenesis. Thus, YKL-40 could be a new therapeutic target for patients with cancer. T-ChOS™ is a technical name for a food supplement product that is marketed in Iceland under the name Benecta™. T-ChOS is manufactured using shellfish derived chitin as a raw material and is produced by Genis in Iceland. It is a blend of chitooligosaccharides that are hetero-complexes of N-acetyl-glucosamine and D-glucosamine. T-ChOS chitooligosaccharides have been specially selected to have high bioactivity in inflammatory models and strong binding affinity to YKL-40. Chitooligosaccharide induced blockade of YKL-40 signalling pathways may represents a promising approach. Pharmacokinetic profile of the T-ChOS in patients with advanced solid malignancies is not available. Safety and tolerability data will be collected to expand the safety/tolerability database for patients with advanced solid malignancies treated with oral T-ChOS. Patients will be allowed to receive T-ChOS on a continuous basis and therefore have the possibility to gain clinical benefit, if any. Safety and tolerability data collected after pharmacokinetic part of the study will be also added to the safety database for patients with advanced solid malignancies treated with oral T-ChOS.

Official Title
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A Single Center, Open-Label, Phase 1 Study to Evaluate the Pharmacokinetic Profile of T-ChOS™ in Subjects With Advanced Solid Tumors (CHITIN)

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Dietary Supplement: T-ChOS


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Signed written Informed Consent Male or females aged 18 to 75 years at the time of signing the informed consent form (ICF) Patients must have histological confirmed malignancy (solid tumor) that is metastatic or unresectable and for which standard curative or palliative therapies do not exist or are no longer effective Understand and voluntarily sign an ICF prior to any study related assessments or procedures being conducted Performance status 0-1 (ECOG) Life expectancy ≥ 3 months Elevated blood YKL-40 > 40 μg/L, assessed within 28 days prior to the start of the study Hematopoietic Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L Platelet count ≥ 100 x 10⁹/L Haemoglobin ≥ 5.6 mmol/L Hepatic Serum bilirubin < 1.5 x upper limit of normal (ULN) AST/ALT < 2.5 x ULN (< 5 x ULN with known liver metastasis) Renal Acceptable renal function with a creatinine clearance ≥ 50 mL/min/ (e.g., using the Cockroft-Gault formula) Cardiovascular No severe or uncontrolled cardiac condition Pulmonary No severe or uncontrolled pulmonary condition Immunologic No known or suspected allergy to the investigational product Gastrointestinal No chronic enteropathy (e.g. active inflammatory bowel disease, extensive intestinal resection or chronic diarrhea) No bowel obstruction or sub-obstruction No prior history of intestinal malabsorption Patients have to be able to swallow normally and have to be willing to comply with the intake of capsules Others No psychiatric condition that would preclude study participation No co-existing active infection requiring antibiotics or any co-existing medical conditions likely to interfere with study procedures No other condition that will preclude study participation A negative pregnancy test for women of childbearing potential. For men and women of child-producing potential, the use of effective contraceptives methods during the study and at least 3 months after discontinuations of the investigational product is required. The following contraceptive methods are regarded as effective: intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release). Sterilised or infertile patients are exempt from the requirement to use contraception. In order to be considered sterilised or infertile, patients must generally have undergone surgical sterilisation (vasectomy/bilateral tubectomy, hysterectomy or bilateral ovariectomy) or be postmenopausal defined as 12 months or more with no menses prior to enrolment Not pregnant or nursing Be able to adhere to the study visit schedule and other protocol requirements EXCLUSION CRITERIA: Simultaneous participation in any other study involving investigational drugs or having participated in a study within 2 weeks prior to start of study treatment Current use of anticoagulation therapy such as heparins both unfractionated and low molecular weighted Symptomatic brain metastases Intake of any prohibited concomitant medication Prior and Concurrent Therapy at least 2 weeks prior to 1st dosing: Biologic/immunotherapy Chemotherapy Radiotherapy Major or laparoscopic surgery Other concurrent anticancer therapy Corticosteroids or other immunosuppressive medications. Inhaled or topical steroids are permitted.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>The active substance used in the T-ChOS capsule formulation is a chitooligosaccharide blend. | Dietary Supplement: T-ChOS<br>* T-ChOS 600 mg (two capsules, each 300 mg) daily in the morning 30 minutes before food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters will be assessed for T-ChOS | • time to reach maximum plasma concentration (tmax) | Approximately up to 12 months | 
| Pharmacokinetic parameters will be assessed for T-ChOS | • area under the plasma concentration-time curve from zero to the last measurable time point (AUC0-t) | Approximately up to 12 months | 
| Pharmacokinetic parameters will be assessed for T-ChOS | • area under the plasma concentration-time curve from zero to infinity (AUC) | Approximately up to 12 months | 
| Pharmacokinetic parameters will be assessed for T-ChOS | • apparent plasma clearance following oral administration (CL/F) | Approximately up to 12 months | 
| Pharmacokinetic parameters will be assessed for T-ChOS | • terminal half-life (t½) | Approximately up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments. | Approximately up to 18 months. | 
| Overall response rate (ORR) | ORR = complete response + partial response, according to RECIST 1.1 | Approximately up to 18 months. | 
| Disease control rate (DCR) | DCR = complete response + partial response + stable disease, according to RECIST 1.1 | Approximately up to 18 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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YKL-40, Pharmacokinetic, Solid tumors, T-ChOS, Benecta, chitinase 3 like-1 protein (CHI3L1)