Delving into the Latest Updates on Palifosfamide Tromethamine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

IPM-tris, Ifosfamide mustard, Ifosforamide mustard

+ [11]

Target-

Mechanism-

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesOther Diseases

Active Indication

Osteosarcoma

Inactive Indication

Advanced cancerAdvanced Malignant Solid NeoplasmAdvanced Sarcoma+ [14]

Originator Organization

DEKK-TEC, Inc.

Active Organization

Phoenix Children's Hospital

Inactive Organization

Alaunos Therapeutics, Inc.

DEKK-TEC, Inc.

Drug Highest PhasePreclinical

First Approval Date-

RegulationOrphan Drug (US)

Login to view timeline

Structure/Sequence

Molecular FormulaC4H11Cl2N2O2P

InChIKeyBKCJZNIZRWYHBN-UHFFFAOYSA-N

CAS Registry31645-39-3

View All Structures (2)

Phase II, randomized, safety and efficacy study in recurrent/metastatic breast cancer with accessible lesions.
Primary End point is rate of Progression Free Survival (PFS) at the 16 week treatment time point. Hypothesis: Adenoviral vector (Ad-RTS-hIL-12) alone and in combination with chemotherapy (palifosfamide) is safe and efficacious.

Start Date01 Mar 2013

Sponsor / Collaborator

Alaunos Therapeutics, Inc.

NCT01808534

/ TerminatedPhase 2IIT

Multicenter Single Arm Phase II Study of Single Agent Palifosfamide in Recurrent and Incurable Germ Cell Tumors

This phase II trial studies how well palifosfamide works in treating patients with recurrent germ cell tumors. Drugs used in chemotherapy, such as palifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing

Start Date01 Feb 2013

Sponsor / Collaborator

The Indiana University School of Medicine

[+1]

NCT01555710

/ Unknown statusPhase 3

A Multi-center, Open-Label, Adaptive, Randomized Study of Palifosfamide-tris, a Novel DNA Crosslinker, in Combination With Carboplatin and Etoposide (PaCE) Chemotherapy Versus Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients With Extensive-Stage Small Cell Lung Cancer. The MATISSE Study

This is a multinational, multicenter, randomized controlled, open-label, adaptive study to evaluate the efficacy of PaCE chemotherapy in chemotherapy naive subjects with extensive-stage SCLC. Eligible subjects will be stratified according to age, gender, and Eastern Cooperative Oncology Group (ECOG) performance status, and randomized in a 1:1 ratio to receive either PaCE or CE chemotherapy.
The study design uses an adaptive group sequential approach with sample size re-estimation at the interim analysis.
Secondary efficacy endpoints include ORR, PFS, duration of response and changes in QOL and disease-related symptoms. Tumor-related endpoints will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.
The safety of study treatments will be assessed by the frequency and severity of adverse events as determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. To provide an initial confirmation of safety, an early interim analysis of safety data only will be performed.
An independent Data Monitoring Committee (DMC) will be convened to assess the safety and efficacy of the study interventions and to monitor the overall conduct of the clinical trial.

Start Date01 May 2012

Sponsor / Collaborator

Alaunos Therapeutics, Inc.

100 Clinical Results associated with Palifosfamide Tromethamine

Login to view more data

100 Translational Medicine associated with Palifosfamide Tromethamine

Login to view more data

100 Patents (Medical) associated with Palifosfamide Tromethamine

Login to view more data

55

Literatures (Medical) associated with Palifosfamide Tromethamine

01 Apr 2023·Environmental science and pollution research international

Environmental performance of phytosanitary control techniques on soybean crop estimated by life cycle assessment (LCA).

Article

Author: Barizon, Robson Rolland Monticelli ; Ralisch, Ricardo ; Lucas, Kassio Ricardo Garcia ; Possamai, Edivan Jose ; Folegatti-Matsuura, Marilia Ieda da Silveira ; Ventura, Mauricio Ursi ; Mrtvi, Paulo Roberto

Phytosanitary control is essential to ensure agricultural productivity and quality. However, approaches based on scheduled use of pesticides, overuse of harmful molecules produce impacts on different types of living organisms. Integrated Pest and Disease Management (IPM-IDM) may significantly reduce the burden of pesticides in the environment. Plant resistance may also be included in the IPM-IDM and even in conventional management due to little requirement of additional knowledge and changes in agricultural practices. Robust environmental assessments using methodology of universal use, life cycle assessment (LCA), may estimate the impacts of specific pesticides that cause major damages, including remarkable category impacts. Therefore the objective of this study was to determine the impacts and (eco)toxicological effects of phytosanitary strategies (IPM-IDM including or not lepidopteran resistant transgenic cultivars) vs. the scheduled approach. Two inventory modeling methods were also applied to gather information on the use and applicability of these methods. Life cycle assessment (LCA) was applied using two inventory modeling methods: 100%Soil and PestLCI (Consensus) using data from Brazilian croplands under tropical conditions, by combining phytosanitary approaches (IPM-IDM, IPM-IDM + transgenic cultivar, conventional, conventional + transgenic cultivar) and modeling methods. Hence, eight soybean production scenarios were established. The IPM-IDM was efficient to reduce the (eco)toxicity impacts of soybean production mainly for freshwater ecotoxicity category. Due to the dynamic character of IPM-IDM approaches, the inclusion of recently introduced strategies (plant resistant and biological control to stink bugs and plant fungal diseases) may diminish even more the principal impacting substances throughout the Brazilian croplands. The PestLCI Consensus method, although its development is yet in progress, to date can be suggested to estimate the agriculture environmental impacts more properly under tropical conditions.

01 Dec 2021·Molecular Cancer TherapeuticsQ2 · MEDICINE

Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial

Q2 · MEDICINE

Article

Author: Coindre, Jean-Michel ; Valverde, Claudia ; Gutierrez, Antonio ; Renne, Salvatore L. ; Collini, Paola ; Merlo, Domenico Franco ; Romagosa, Cleofe ; Palmerini, Emanuela ; Casali, Paolo G. ; Dei Tos, Angelo Paolo ; Bagué, Silvia ; Barisella, Marta ; Hindi, Nadia ; Braglia, Luca ; Gambarotti, Marco ; Grignani, Giovanni ; Gronchi, Alessandro ; Martin-Broto, Javier ; Velasco, Valerie ; Ramos, Rafael ; Moura, David S. ; Lopez-Pousa, Antonio ; Quagliuolo, Vittorio L. ; Brunello, Antonella ; Dopazo, Joaquin ; Blay, Jean-Yves ; Stacchiotti, Silvia ; Lopez-Lopez, Daniel ; Lopez-Alvarez, Maria ; Picci, Piero

AbstractMRP-1 is implicated in multidrug resistance and was described as prognostic in high-risk patients with soft-tissue sarcoma (STS) in a previous study. The current research aimed to validate MRP-1 prognostic/predictive value in localized sarcomas treated with anthracyclines plus ifosfamide within the ISG-1001 phase III study. In addition, the inhibitory activity on MRP-1 was investigated in preclinical studies to identify new combinations able to increase the efficacy of standard chemotherapy in STS. MRP-1 expression was assessed by IHC in tissue microarrays from patients with STS and tested for correlation with disease-free survival (DFS) and overall survival (OS). In vitro studies tested the efficacy of MRP-1 inhibitors (nilotinib, ripretinib, selumetinib, and avapritinib) in sarcoma cell lines. The effect of combinations of the most active MRP-1 inhibitors and chemotherapy was measured on the basis of apoptosis. MRP-1 was evaluable in 231 of 264 cases who entered the study. MRP-1 expression (strong intensity) was independently associated with worse DFS [HR, 1.78; 95% confidence interval (CI), 1.11–2.83; P = 0.016], in the multivariate analysis, with a trend for a worse OS (HR, 1.78; 95% CI, 0.97–3.25; P = 0.062). In vitro studies showed that the addition of MRP-1 inhibitors (nilotinib or avapritinib) to doxorubicin plus palifosfamide, significantly increased cell death in SK-UT-1 and CP0024 cell lines. MRP-1 is an adverse predictive factor in localized high-risk patients with STS treated with neoadjuvant anthracyclines plus ifosfamide followed by surgery. In vitro findings support the clinical assessment of the combination of chemotherapy and MRP-1 inhibitors as a promising strategy to overcome the drug ceiling effect for chemotherapy.

01 Dec 2021·Journal of the Egyptian National Cancer Institute

An in vitro cytotoxicity of glufosfamide in HepG2 cells relative to its nonconjugated counterpart

Article

Author: Abdelhakim, Heba K ; Arafa, Hossam M M ; Mohamed, Amr S ; Ahmed, Doaa E ; Rashidi, Fatma B

AbstractBackgroundGlufosfamide (β-d-glucosylisophosphoramide mustard, GLU) is an alkylating cytotoxic agent in which ifosforamide mustard (IPM) is glycosidically linked to the β-d-glucose molecule. GLU exerted its cytotoxic effect as a targeted chemotherapy. Although, its cytotoxic efficacy in a number of cell lines, there were no experimental or clinical data available on the oncolytic effect of oxazaphosphorine drugs in hepatocellular carcinoma. Therefore, the main objective of the current study is to assess the cytotoxic potential of GLU for the first time in the hepatocellular carcinoma HepG2 cell line model.MethodsCytotoxicity was assayed by the MTT method, and half-maximal inhibitory concentration (IC50) was calculated. Flow cytometric analysis of apoptosis frequencies was measured by using Annexin V/PI double stain, an immunocytochemical assay of caspase-9, visualization of caspase-3, and Bcl2 gene expression were undertaken as apoptotic markers. Mitochondrial membrane potential was measured using the potentiometric dye; JC-1, as a clue for early apoptosis as well as ATP production, was measured by the luciferase-chemiluminescence assay.ResultsGlufosfamide induced cytotoxicity in HepG2 cells in a concentration- and time-dependent manner. The IC50 values for glufosfamide were significantly lower compared to ifosfamide. The frequency of apoptosis was much higher for glufosfamide than that of ifosfamide. The contents of caspase-9 and caspase-3 were elevated following exposure to GLU more than IFO. The anti-apoptotic Bcl2 gene expression, the mitochondrial membrane potential, and the cellular ATP levels were significantly decreased than in case of ifosfamide.ConclusionsThe current study reported for the first time cytotoxicity activity of glufosfamide in HepG2 cells in vitro. The obtained results confirmed the higher oncolytic activity of glufosfamide than its aglycone ifosfamide. The generated data warrants further elucidations by in vivo study.

1

News (Medical) associated with Palifosfamide Tromethamine

08 Jun 2010

·www.biospace.com

ZIOPHARM, Inc. Presents Positive Palifosfamide PICASSO Phase II Results in Oral Session at American Society of Clinical Oncology

NEW YORK--(BUSINESS WIRE)--ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) announced today that Dr. Claire Verschraegen of the University of New Mexico, Albuquerque and first author of the abstract, “A phase II randomized controlled trial of palifosfamide plus doxorubicin vs. doxorubicin in patients with soft tissue sarcoma (PICASSO),” (Abstract #10004) presented in an oral session today updated positive data from PICASSO. The presentation was part of the 46th Annual American Society of Clinical Oncology (ASCO) meeting being held in Chicago, IL, from June 4th to 8th. The abstract has also been selected as part of the 2010 Best of ASCO® which features high-impact abstracts from the ASCO Annual Meeting that represent the most relevant, cutting-edge science in oncology today.

ASCO

100 Deals associated with Palifosfamide Tromethamine

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D10373	-	-	DB05668

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Soft Tissue Sarcoma	Phase 2	PA	Alaunos Therapeutics, Inc.	01 Jul 2010
Metastatic Soft Tissue Sarcoma	Phase 2	SG	Alaunos Therapeutics, Inc.	01 Jul 2010
Metastatic Soft Tissue Sarcoma	Phase 2	CL	Alaunos Therapeutics, Inc.	01 Jul 2010
Metastatic Soft Tissue Sarcoma	Phase 2	DE	Alaunos Therapeutics, Inc.	01 Jul 2010
Metastatic Soft Tissue Sarcoma	Phase 2	AR	Alaunos Therapeutics, Inc.	01 Jul 2010
Metastatic Soft Tissue Sarcoma	Phase 2	CA	Alaunos Therapeutics, Inc.	01 Jul 2010
Small Cell Lung Cancer	Phase 2	-	DEKK-TEC, Inc.	-
Metastatic Soft Tissue Sarcoma	Phase 1	IT	Alaunos Therapeutics, Inc.	01 Jul 2010
Metastatic Soft Tissue Sarcoma	Discovery	GB	Alaunos Therapeutics, Inc.	01 Jul 2010
Metastatic Soft Tissue Sarcoma	Discovery	BE	Alaunos Therapeutics, Inc.	01 Jul 2010

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01555710 (MATISSE, Pubmed \| J Urol) Manual	Phase 3	Extensive stage Small Cell Lung Cancer	188	Palifosfamide+Carboplatin+Etoposide	(czcatcmbbz) = tkjjujkljj ntekteklxu (uzdningpnl )	Negative	10 Aug 2017
				Carboplatin+Etoposide	(czcatcmbbz) = tjkhxccvfn ntekteklxu (uzdningpnl )
NCT01168791 (PICASSO III, Pubmed \| J Urol \| J Clin Oncol) Manual	Phase 3	Metastatic Soft Tissue Sarcoma	447	Doxorubicin+Palifosfamide	(jxwtznnalt) = ioqqrgxdbf ttgdirsktd (eqrjahyojs ) View more	Negative	10 Nov 2016
				Doxorubicin+Placebo	(jxwtznnalt) = fotwpwqwtg ttgdirsktd (eqrjahyojs ) View more
NCT01808534 (CTgov)	Phase 2	germ cell cancers \| Seminoma \| Teratoma \| Recurrent Malignant Extragonadal Germ Cell Tumor \| Ovarian Germ Cell Cancer \| Nonseminomatous Germ Cell Tumor \| Testicular Germ Cell Tumor	5	palifosfamide	(cvxxeskblh) = ewsauxduqz uznhxoehgu (ffgqocgyun, aptyxnplxq - akrdnosccn) View more	-	02 Jul 2015
NCT01555710 (MATISSE, ASCO2015)	Phase 3	Extensive stage Small Cell Lung Cancer First line	188	Carboplatin and etoposide (CE)	(xrafvpwlrc) = zdplamsbjg ffruvwycrn (lhhirsvsui )	Negative	20 May 2015
				Palifosfamide (Pa) + Carboplatin and etoposide (CE)	(xrafvpwlrc) = mddgaauvov ffruvwycrn (lhhirsvsui )
NCT00718484 (PICASSO, ASCO2010)	Phase 2	Sarcoma Second line	-	Palifosfamide + Doxorubicin	(xkaxbememc) = bsdqidmred tvkjdvvtmx (fqmomwzyte )	Positive	20 May 2010
				Doxorubicin	(xkaxbememc) = tfyrwwjspm tvkjdvvtmx (fqmomwzyte )
ASCO2009	Phase 1	Neoplasms	13	Palifosfamide	(hogfxensmv) = mdbrqzgzew znukrekykp (psfzxbrmfj )	-	20 May 2009
ASCO2006	Phase 1	Neoplasms	18	ZIO-201	sljdyahdgy(akyiqdojhv) = rfetjdaeyp uxscvokcwj (lkrtohmflk ) View more	-	20 Jun 2006