Antineoplastic Agents

All Drugs and Chemicals

Antimitotic Agents

GSK923295

GSK Clinical Trials

This is a Phase I, open-label, first time in human study of GSK923295, in adult subjects with cancers that do not respond to standard therapy. This study will be conducted in two stages; a dose-escalation stage (Stage 1) and an expansion cohort stage (Stage 2).

Centromere-associated protein E (CENP-E) is a protein that is required for correct chromosomal alignment in mitosis. Loss of CENP-E activity, due to microinjection of antibodies, ablation of gene expression with siRNA or antisense oligonucleotides, or inhibition of enzymatic activity by small molecule inhibitors, causes aberrant cell cycle arrest in mitosis, characterized by a bipolar mitotic spindle with misaligned chromosomes. Studies with small molecule inhibitors have demonstrated that this aberrant cell cycle arrest can result in apoptosis and cell death. CENP-E has been shown to be abundantly expressed in a variety of human tumors. GSK923295 is a potent and selective CENP-E inhibitor which has demonstrated potent and broad spectrum antitumor activity against solid and hematologic malignancies in vitro. GSK923295 is intended for use either as a monotherapy or in combination with existing anti-cancer therapies.

A drug targeting CENP-E may prove as efficacious as the taxanes and vinca alkaloids, without the potential for neurotoxicity or other side-effects associated with interference of tubulin function in non-dividing cells. Similar to many other anti-proliferative drugs, CENP-E inhibitors are expected to have manageable dose-limiting toxicities resulting from action on normal proliferating tissues (e.g., myelosuppression and gastrointestinal epithelial cell damage). The opportunity for inhibitors of CENP-E lies in the potential for broad efficacy. The absence of broad clinical experience with anti-mitotic cancer therapies acting on targets other than tubulin complicates prediction of additional benefits, beyond the lack of neurotoxicity that might accrue from a drug targeting CENPE.

The purpose of this Phase I, first time in human (FTIH) study in subjects with refractory cancers is to determine the maximally tolerated dose (MTD) (or recommended dose based on available safety, pharmacokinetic (PK) and response data), dose-limiting toxicities (DLTs), PK, pharmacodynamics (PD), and preliminary clinical activity of GSK923295, an inhibitor of CENP-E.

The primary objectives in Stage 1 (Dose Escalation) are:

• To determine the MTD (or recommended dose based on available safety, PK, and response data), DLTs, safety, and PK of GSK923295 administered to subjects with advanced, refractory malignancies.

The primary objectives in Stage 2 (Expansion Cohort) are:

• To evaluate the safety and PK of GSK923295 at the MTD (or recommended dose based on available safety, PK, and response data) administered to subjects with advanced, refractory malignancies.

Secondary Objectives in the study are:

* To determine the clinical activity of GSK923295 administered to subjects with advanced, refractory malignancies.
* To evaluate the effect of GSK923295 on biomarkers in normal host tissue (Stage 1 and 2) and tumor (Stage 2, optional in Stage 1) and the effect of GSK923295 on tumor metabolism with FDG-PET imaging (Stage 2, optional in Stage 1).
* Explore associations between biochemical and genetic characteristics of baseline archival tumor specimens (Stage 1 and Stage 2), biopsy-accessible tumor specimens (Stage 2), and anti-tumor response.
* Explore pharmacogenomic associations between genetic variants in drug metabolizing and drug transport genes and PK, safety, and efficacy of GSK923295.

The primary and secondary endpoint(s) used to assess the objective measures are:

Primary

• Adverse events (AE) and changes from baseline in vital signs, clinical laboratory parameters, and electrocardiography (ECG) assessments will be evaluated to assess safety profile.

Secondary

* The MTD (or recommended dose based on available safety, PK, and response data) where no more than 1 of 6 subjects has a DLT in the first treatment cycle.
* PK parameters CL, Vdss, AUC(0-∞), AUC(0-t), Cmax, tmax, and t1/2 (Stage 1) and develop a PK model for GSK923295 (Stage 1 and 2).
* Anti-tumor activity measurements will be obtained at baseline and after every second cycle according to the following:
* Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines for solid tumors (for solid tumors and non-Hodgkin's lymphoma).
* National Cancer Institute - Working Group (NCI-WG) Guidelines for chronic lymphocytic leukaemia.
* Exploratory PK/PD modeling of safety and response data.
* Changes in biomarkers of cell proliferation and cell death or imaging endpoints.
* Biomarker profiles in archival tumor specimens and their correlation with clinical activity.
* Genetic polymorphisms in key enzymes involved in the metabolism and disposition of GSK923295 and correlations with pharmacokinetic, safety, and response (pharmacodynamic) data.

The study will consist of two stages. Stage 1 consists of a dose escalation stage to determine the MTD (or recommended dose based on available safety, PK and response data) using an accelerated titration scheme combined with standard dose escalation methods. GSK923295 will be administered intravenously over one hour, once weekly for 3 consecutive weeks (i.e., Day 1, 8, and 15) with treatment cycles repeated every 4 weeks (each cycle = 28 days). During Stage 1, safety, pharmacokinetics, pharmacodynamics, and clinical activity will be assessed. Tumor biopsies and PET imaging are optional in Stage 1 subjects. The MTD (or recommended dose based on available safety, PK and response data) will be defined as the dose of GSK923295 at which no more than 1 of 6 subjects experiences a DLT in the first treatment cycle. Eighteen subjects are anticipated to participate in Stage 1 of the study. In Stage 2, 15-20 additional subjects will be enrolled at the MTD (or recommended dose based on available safety, PK and response data) dose to further evaluate the safety of GSK923295. In Stage 2, PK samples (using a sparse PK sampling scheme for population PK analyses), PET imaging, and tumor biopsies will be obtained. Clinical activity will be assessed. Subjects (Stage 1 and Stage 2) will remain on study until they meet the criteria for treatment discontinuation described in the protocol. It is anticipated that 33-38 subjects will participate in the study (18 in Stage 1 and 15-20 in Stage 2. During Stage 1 and Stage 2, subjects with histologically confirmed advanced refractory solid tumors will be enrolled. In Stage 2, subjects with refractory non-Hodgkin's lymphoma and chronic lymphocytic leukemia can also be enrolled.

Phase I Study to Assess the Safety, Pharmacokinetics, & Pharmacodynamics of GSK923295 in Subjects w/ Refractory Cancer

A Phase I, Open-Label, Dose-Escalation, First Time in Human Study to Evaluate the Safety Profile, Pharmacokinetics, and Pharmacodynamics of GSK923295 in Subjects With Refractory Cancers

used to measure levels of the drug in blood over time

used to monitor levels of the drug in blood

GlaxoSmithKline

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.

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

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

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

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

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.

Intravenous drug administration, with different doses in each cohort

Amblyomin-X

Paula F Santos

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.

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.

Study with dose escalation regime, done according to the classic scheme known as "3 + 3"

Study of Amblyomin-X in Advanced Solid Tumor

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

Presence of grade 4 or non-haematological grade 3 haematological toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4)

This will be based on dose-limiting toxicity of the previous cohort

Buranello e Rodrigues Consultoria em Desenvolvimento Farmacêutico Ltda ME

União Química Farmacêutica Nacional S/A

Micronutrients

Hematinics

Vitamins

Gemcitabine

Pemetrexed

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

gemcitabine administered in combination with AZD6918

pemetrexed administered in combination with AZD6918

AZD6918

intravenous, doses are on an intermittent schedule

gemcitabine

intravenous, dose administered every 21-days

pemetrexed

Judith Ochs, MD

Jeffrey Infante, MD

Lia Gore, MD

The primary purpose of this study is to find out what the maximum tolerated dose is for an experimental drug called AZD6918 based on the side effects experienced by patients with advanced solid malignancies that receive daily AZD6918 alone. It is possible that AZD6918 will be administered twice daily. Then maximum tolerated doses in combination with either gemcitabine or pemetrexed will also be investigated.

Phase I, Open-label, Dose-escalation, Safety and PK Study of AZD6918

A Phase I, Open-Label, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6918 Administered Daily as a Single Agent and in Combination Treatment in Adult Patients With Refractory Solid Malignancies

AstraZeneca

Judith Ochs, M.D. Medical Science Director

Central Nervous System Depressants

Psychotropic Drugs

Gastrointestinal Agents

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Fluvoxamine

Serotonin

Lactitol

Vadimezan

ASA404 + Fluvoxamine (Core Phase), ASA404 + either paclitaxel or docetaxel or paclitaxel plus carboplain chemotherapy combination (Extension Phase)

Vadimezan™

Novartis Pharmaceuticals

This trial is designed to study the drug-drug interaction between ASA404 and fluvoxamine, an inhibitor of its metabolic pathway (CYP1A2). The study will consist of two phases. The purpose of the Core Phase is to study the drug drug interaction between fluvoxamine and ASA404. The purpose of the Extension Phase is to provide continued treatment for those patients that have not progressed during the Core Phase and to collect safety data on ASA404 when given in combination with paclitaxel, docetaxel or the paclitaxel plus carboplatin chemotherapy regimen.

Safety and Pharmacokinetics of ASA404 When Given Together With Fluvoxamine, a Selective Serotonin Receptor Reuptake Inhibitor and CYP1A2 Inhibitor

A Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effects of Fluvoxamine on the Pharmacokinetics of ASA404 in Adult Patients With Solid Tumor Malignancies

Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

LGH447

This is a multi-center, open-label, dose escalation, Phase 1 study of oral LGH447 in Japanese patients with relapsed and/or refractory multiple myeloma for which no standard effective treatment options exist.

The study consists of a dose escalation part to estimate the maximum tolerated dose and/or the recommended dose for expansion and a dose expansion part to further assess safety and preliminary anti-cancer activity of LGH447 at the maximum tolerated dose and/or the recommended dose for expansion.

Dose Escalation Study of LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies

A Multi-center, Open-label, Dose Escalation, Phase 1 Study of Oral LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies

Estimate the maximum tolerated dose and/or recommended dose for expansion of LGH447 in Japanese patients

Adverse events, serious adverse events, changes in laboratory values, and electrocardiograms

PK parameters such as AUC, Cmax, Tmax, T1/2. Cycle = 28 days

Describe any preliminary anti-cancer activity associated with LGH447 based on International Myeloma Working group Criteria with modification.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Study to Assess the Safety, Pharmacokinetics, & Pharmacodynamics of GSK923295 in Subjects w/ Refractory Cancer	NCT00504790	Cancer	GSK923295	18 Years -	GlaxoSmithKline
Study of Amblyomin-X in Advanced Solid Tumor	NCT03120130	Advanced Cancer	Amblyomin-X	18 Years - 75 Years	União Química Farmacêutica Nacional S/A
Phase I Study to Assess the Safety, Pharmacokinetics, & Pharmacodynamics of GSK923295 in Subjects w/ Refractory Cancer	NCT00504790	Cancer	GSK923295	18 Years -	GlaxoSmithKline
Study of Amblyomin-X in Advanced Solid Tumor	NCT03120130	Advanced Cancer	Amblyomin-X	18 Years - 75 Years	União Química Farmacêutica Nacional S/A
Phase I, Open-label, Dose-escalation, Safety and PK Study of AZD6918	NCT00733031	Cancer, Solid Tumors Advanced Solid ...	AZD6918 gemcitabine pemetrexed	18 Years -	AstraZeneca
Safety and Pharmacokinetics of ASA404 When Given Together With Fluvoxamine, a Selective Serotonin Receptor Reuptake Inhibitor and CYP1A2 Inhibitor	NCT01299415	Solid Tumors	Vadimezan™	18 Years -	Novartis
Dose Escalation Study of LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies	NCT02160951	Multiple Myelom...	LGH447	18 Years -	Novartis

Spots Global Cancer Trial Database for phase i,

Every month we try and update this database with for phase i, cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for phase i,

Every month we try and update this database with for phase i, cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for phase i, cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.