Delving into the Latest Updates on Topotecan Liposomal(Inex Pharmaceuticals) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Liposomal Drug

Synonyms

Brakiva

Target

Top I

Action

inhibitors

Mechanism

TOP1 inhibitors(DNA topoisomerase I inhibitors)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseRespiratory Diseases+ [2]

Active Indication-

Inactive Indication

Advanced Cervical CarcinomaAdvanced Malignant Solid NeoplasmCervical Squamous Cell Carcinoma+ [5]

Originator Organization

Inex Pharmaceuticals

Active Organization-

Inactive Organization

Spectrum Pharmaceuticals, Inc.

National Cancer InstituteInex Pharmaceuticals

License Organization

Arbutus Biopharma Corp.

Talon Therapeutics, Inc.

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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A multi-center, open-label, two-arm, dose-escalation study to establish the safety, tolerability, MTD, and schedule of TLI administered intravenously as a 30 minute infusion in adult subjects with advanced solid tumors that have relapsed, are refractory to standard therapy, or for whom there is no standard therapy available.
The two dosing regimens to be evaluated are:
Arm A: TLI dose on Days 1 and 8 of a 21-day treatment cycle (Starting dose: 1 mg/m2)
Arm B: TLI dose on Day 1 of a 21-day treatment cycle (Starting dose: 2 mg/m2)
When one of the two arms reaches MTD, all future subjects will then be enrolled in the remaining study arm until MTD of that arm is reached.

Start Date10 Nov 2008

Sponsor / Collaborator

Spectrum Pharmaceuticals, Inc.

NCT00054444

/ CompletedPhase 1IIT

A PHASE I STUDY OF PELVIC RADIATION THERAPY WITH CONCOMITANT WEEKLY CISPLATIN AND TOPOTECAN CHEMOTHERAPY IN PATIENTS WITH CERVICAL CARCINOMA WITHOUT EXTRA-PELVIC METASTASIS

This phase I trial is studying the side effects and best way to give radiation therapy when given together with topotecan and cisplatin in treating patients with locally advanced cervical cancer. This trial is also studying the best dose of topotecan when given in this regimen. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as topotecan and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

Start Date01 Sep 2007

Sponsor / Collaborator

The Gynecologic Oncology Group

[+1]

100 Clinical Results associated with Topotecan Liposomal(Inex Pharmaceuticals)

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100 Translational Medicine associated with Topotecan Liposomal(Inex Pharmaceuticals)

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100 Patents (Medical) associated with Topotecan Liposomal(Inex Pharmaceuticals)

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3

Literatures (Medical) associated with Topotecan Liposomal(Inex Pharmaceuticals)

01 Jan 2016·Critical Reviews™ in Therapeutic Drug Carrier SystemsQ3 · MEDICINE

Topotecan Liposomes: A Visit from a Molecular to a Therapeutic Platform

Q3 · MEDICINE

Review

Author: Jain, Ankit ; Hurkat, Pooja ; Saraf, Shivani ; Jain, Sanjay Kumar

Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases. This review discusses these problems and the means to overcome them, including modification of TLs using zwitterionic poly(carboxybetaine), prolongation in dosing interval (long-term therapy), and modified liposomal encapsulation techniques including active loading methods. We also explore engineered TLs (surface and integral modifications) such as PEGylated TLs, ligand-anchored TLs, and stimuli-sensitive TLs. Further, potential applications, manifestations at the molecular level, patents granted, and preclinical and clinical outlook for TLs are discussed.

01 Jan 2006·International journal of nanomedicine

Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential.

Review

Author: Immordino, Maria Laura ; Cattel, Luigi ; Dosio, Franco

Among several promising new drug-delivery systems, liposomes represent an advanced technology to deliver active molecules to the site of action, and at present several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles ("first-generation liposomes") to "second-generation liposomes", in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol) (PEG) in liposome composition. The presence of PEG on the surface of the liposomal carrier has been shown to extend blood-circulation time while reducing mononuclear phagocyte system uptake (stealth liposomes). This technology has resulted in a large number of liposome formulations encapsulating active molecules, with high target efficiency and activity. Further, by synthetic modification of the terminal PEG molecule, stealth liposomes can be actively targeted with monoclonal antibodies or ligands. This review focuses on stealth technology and summarizes pre-clinical and clinical data relating to the principal liposome formulations; it also discusses emerging trends of this promising technology.

01 Jul 2000·Cancer research

Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models.

Article

Author: Redelmeier, T ; Tardi, P ; Bally, M ; Madden, T D ; Choice, E ; Masin, D

Topotecan was encapsulated in sphingomyelin/cholesterol liposomes using an ionophore-generated proton gradient. After i.v. injection, liposomal topotecan was eliminated from the plasma much more slowly than free drug, resulting in a 400-fold increase in plasma area under the curve. Further, high-performance liquid chromatography analysis of plasma samples demonstrated that topotecan was protected from hydrolysis within the liposomal carrier with >80% of the drug remaining as the active, lactone species up to 24 h. The improved pharmacokinetics observed with liposomal topotecan correlated with increased efficacy in both murine and human tumor models. In the L1210 ascitic tumor model, optimal doses of liposomal topotecan resulted in a 60-day survival rate of 60-80%, whereas in a L1210 liver metastasis model, 100% long-term survival (>60 days) was achieved. In contrast, long-term survivors were rarely seen after treatment with free topotecan. Further, in a human breast carcinoma model (MDA 435/LCC6), liposomal topotecan provided greatly improved increase in life span relative to the free drug. These results suggest that liposomal encapsulation can significantly enhance the therapeutic activity of topotecan.

100 Deals associated with Topotecan Liposomal(Inex Pharmaceuticals)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	United States	Spectrum Pharmaceuticals, Inc.	10 Nov 2008
Ovarian Cancer	Phase 1	United States	Spectrum Pharmaceuticals, Inc.	10 Nov 2008
Small Cell Lung Cancer	Phase 1	United States	Spectrum Pharmaceuticals, Inc.	10 Nov 2008
Advanced Cervical Carcinoma	Phase 1	United States	National Cancer Institute	01 Sep 2007
Cervical Squamous Cell Carcinoma	Phase 1	United States	National Cancer Institute	01 Sep 2007
Locally Advanced Cervical Carcinoma	Phase 1	United States	National Cancer Institute	01 Sep 2007
Uterine Cervix Adenocarcinoma	Phase 1	United States	National Cancer Institute	01 Sep 2007
Neoplasms	Phase 1	-	Inex Pharmaceuticals	01 Jul 2000