Study of Amblyomin-X in Advanced Solid Tumor

Study Overview
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Brief Summary
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Amblyomin-X is an inhibitor of Factor Xa that also acts as an apoptotic agent for tumor cells. In the case of in vitro assays, Amblyomin-X induces tumor cells to death and does not affect the viability of normal cells. When in vivo assays were performed on mice bearing tumors, treatment with Amblyomin-X caused a significant reduction in tumor mass and number of metastases.

Detailed Description
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This trial will be the first clinical study in humans with the product, which until then has been studied only in experimental models. Given the current epidemiological impact of cancer and the need to improve its systemic treatment, making it available to a larger portion of the Brazilian population, it is proposed to conduct the first Amblyomin-X study in cancer patients, more specifically those with advanced solid tumors For which there is no contraindicated or inaccessible therapeutic option established as the standard at the time of inclusion in the study.

Official Title
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Phase I Study (First in Humans) of the Amblyomin-X in the Treatment of Patients With Advanced Solid Tumors Refractory or Without Indication / Access to Standard Treatment

Conditions
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Advanced Cancer

Intervention / Treatment
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* Biological: Amblyomin-X


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients must sign the Free and Informed Consent Term (TCLE), be between 18 and 75 years of age, present a solid tumor proven by anatomopathological examination at an advanced or metastatic stage and refractory to conventional treatment or without current indication or access to conventional treatment , have a life expectancy of at least 12 weeks. presence of measurable disease according to Response Response Criteria in Solid Tumors (RECIST, version 1.1), medullary, renal and hepatic functions within acceptable limits (defined in protocol), end of the previous antineoplastic treatment at least 4 weeks (since the last dose of any antineoplastic medication, radiotherapy, or surgical procedure). Exclusion Criteria: The presence of previously non-irradiated brain metastasis; Prediction of the use of radiotherapy, surgery, systemic antineoplastic treatment, or any other form of treatment for cancer after inclusion in the study; Prediction of corticosteroid use, hematopoietic growth factors or inhibitors of bone resorption during the first course of treatment (4 weeks); Regular use of anticoagulants or known previous coagulation disorder; Severe comorbidity (at the discretion of the researcher); Gestational, lactating, pregnant women, or who have not been surgically infertile or menopausal for at least 12 months; Men and women who refuse to use an adequate contraceptive method during the study period; Participation of another clinical study in the last 12 months (unless justified by the investigator); Or inability to comply with study requirements and procedures.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Study with dose escalation regime, done according to the classic scheme known as 3 + 3
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>This cohort will include 3 patients with the first calculated dose of Amblyomin-X drug. The patient will receive the intravenous drug. If no Dose-limiting toxicity (DLT) in this group the study continues including the next cohort. However, if If only one patient in a given cohort develops DLT, three more patients will be included at that dose level, up to a maximum total of six patients per dose level. If two or more of the three patients of a certain dose level develop DLT, this dose level is considered very toxic, and the study does not proceed. If this occurs at the first dose level, the study will be finalized. If only one in six patients at a dose level develops DLTs, escalation proceeds until Tolerated Maximum Dose. | Biological: Amblyomin-X<br>* Intravenous drug administration, with different doses in each cohort<br>|
| Experimental: Cohort 2<br>This cohort will include 3 patients with the second calculated dose of Amblyomin-X drug. The patient will receive the intravenous drug. If no Dose-limiting toxicity in this group the study continues including the next cohort | Biological: Amblyomin-X<br>* Intravenous drug administration, with different doses in each cohort<br>|
| Experimental: Cohort 3<br>This cohort will include 3 patients with the third calculated dose of Amblyomin-X drug. The patient will receive the intravenous drug. If no Dose-limiting toxicity in this group the study continues including the next cohort | Biological: Amblyomin-X<br>* Intravenous drug administration, with different doses in each cohort<br>|
| Experimental: Cohort 4<br>This cohort will include 3 patients with the fourth calculated dose of Amblyomin-X drug. The patient will receive the intravenous drug. If no Dose-limiting toxicity in this group the study continues including the next cohort | Biological: Amblyomin-X<br>* Intravenous drug administration, with different doses in each cohort<br>|
| Experimental: Cohort 5<br>This cohort will include 3 patients with the fifth calculated dose of Amblyomin-X drug. The patient will receive the intravenous drug. If no Dose-limiting toxicity in this group the study continues including the next cohort | Biological: Amblyomin-X<br>* Intravenous drug administration, with different doses in each cohort<br>|
| Experimental: Cohort 6<br>This cohort will include 3 patients with the sixth calculated dose of Amblyomin-X drug, the last dose calculated. The patient will receive the intravenous drug. | Biological: Amblyomin-X<br>* Intravenous drug administration, with different doses in each cohort<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| grade 4 or non-haematological grade 3 haematological toxicity according to the CTCAE (version 4) | Presence of grade 4 or non-haematological grade 3 haematological toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4) | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose (MTD) and the recommended dose for phase II | This will be based on dose-limiting toxicity of the previous cohort | 2 weeks | 
| Adverse Events | haematological toxicity | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I,