A Phase 3 Randomized, Open-label Comparative Study of Standard Whole Brain Radiation Therapy with Supplemental Oxygen, with or without Concurrent RSR13 (efaproxiral), in Women with Brain Metastases from Breast Cancer - ENRICH study

Start Date14 Feb 2005

Sponsor / Collaborator

Allos Therapeutics, Inc.

NCT00083304

/ CompletedPhase 3

A Phase 3 Randomized, Open-label Comparative Study of Standard Whole Brain Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Women With Brain Metastases From Breast Cancer

RSR13 (efaproxiral) is a radiation sensitizer that has shown positive results in a Phase 3, randomized clinical trial of patients with brain metastases. Of 111 eligible breast cancer patients with brain metastases in that trial, 59 patients who received RSR13 prior to radiation therapy had a median survival time that was twice as long as the 52 patients who did not receive RSR13 prior to radiation therapy.
RSR13 (efaproxiral) is an experimental drug that increases the amount of oxygen released from blood into the tissues. It is well known that certain types of cancer tumors, including those in brain metastases, lack oxygen. Lack of oxygen in a tumor can reduce the effect of radiation therapy (RT). RSR13 may increase the oxygen level in brain tumors so that radiation therapy works better.
This study will enroll up to 360 women with brain metastases from breast cancer, and will evaluate if whole brain radiation therapy given with RSR13 will have a better treatment effect than whole brain radiation therapy alone. RSR13 will be infused intravenously (IV) through a central catheter placed in a central vein. Women randomized (assigned) to receive RSR13, therefore, will need to have a central catheter placed for treatment unless one is already in place.

Start Date01 Feb 2004

Sponsor / Collaborator

Spectrum Pharmaceuticals, Inc.

NCT00055887

/ WithdrawnPhase 3

A Phase III Randomized, Open-Label Comparative Study of Induction Chemotherapy Followed by Thoracic Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Patients With Locally Advanced Unresectable (Stage IIIA/IIIB) Non-Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as efaproxiral may make the tumor cells more sensitive to radiation therapy. It is not yet known if chemotherapy combined with radiation therapy is more effective with or without efaproxiral in treating non-small cell lung cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy combined with radiation therapy with or without efaproxiral in treating patients who have stage III non-small cell lung cancer.

Start Date01 Nov 2002

Sponsor / Collaborator

Spectrum Pharmaceuticals, Inc.

100 Clinical Results associated with Efaproxiral

100 Translational Medicine associated with Efaproxiral

100 Patents (Medical) associated with Efaproxiral

132

Literatures (Medical) associated with Efaproxiral

01 Feb 2025·Analytical and Bioanalytical Chemistry

LC-HRMS screening procedure for the detection of 11 different classes of prohibited substances in dried urine spots for doping control purposes

Article

Author: Tsivou, Maria ; Pizzolato, Francesca ; Honesová, Lenka ; Gmeiner, Günter ; Mazzarino, Monica ; Van Eenoo, Peter

Dried urine spots have recently been proposed as an alternative matrix in the anti-doping field. Drying urine may open the opportunity to limit microbial and thermal degradation of the prohibited substances during transportation to the anti-doping laboratories without the need for refrigeration or freezing. In this study, a multi-targeted initial testing procedure was developed for the determination of 237 prohibited drugs/metabolites from 11 different classes in dried urine spots. The comparability between two different microsampling techniques (i.e., Whatman^® FTA DMPK-C cards and Mitra^® tips) was evaluated. The developed method was then used to evaluate the stability of the target compounds in urine for 7 days under different environmental conditions to simulate the transportation of the urine samples from the collection sites to anti-doping laboratories. Sample preparation consists of (i) extraction of the analytes from the collection device using a mixture of acetonitrile/methanol (1/1) for 30 min at 40 °C, (ii) enzymatic hydrolysis, and (iii) sample concentration by solid-phase extraction. Analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. The entire workflow was validated in terms of specificity (analytes were distinguishable from the matrix interferences), sensitivity (only with the Mitra^® tips the limits of detection comply with the World Anti-Doping Agency's requirements for the majority of the target compounds), carry-over (no signals in the negative urine injected after the positive urine), matrix effect (16-28% for Mitra^® tips and 22-35% for DMPK-C cards), and extraction yield (Mitra^® tips: 51-88%; DMPK-C cards: 40-76%). As proof of concept, authentic urine samples were analyzed: results obtained in dried urine were compared with those of fluid urine, providing good agreement. Stability studies showed that the target compounds were stable for the whole duration of the study (7 days) at -20 and 4 °C in both fluid and dried urine. At 50 °C or at 20-25 °C, several thiazide-based compounds were completely degraded to their degradation product in the first 24 h or after 3-4 days in fluid urine, whereas in dried urine the compounds were detectable for the entire duration of the study.

01 Jul 2024·Journal of Ethnopharmacology

Fangji Huangqi Decoction alleviates rheumatoid arthritis through regulating HIF-1α mediated the angiogenesis and the balance between autophagy and apoptosis

Article

Author: Zhang, Yumeng ; Hao, Huiqin ; Liu, Qi ; Pu, Wei ; Li, Siyuan ; Liu, Yang ; Wang, Yuru ; Xu, Ye

ETHNOPHARMACOLOGICAL RELEVANCEFangji Huangqi Decoction (FHD) is frequently prescribed for the clinical treatment of wind-cold and wind-dampness pathogenic superficial deficiency syndrome. It also has a notable curative effect on rheumatoid arthritis (RA).AIM OF THE STUDYThe study aimed to explore the possible mechanism of FHD against RA and provided a theoretical basis for alternative therapies for RA.MATERIALS AND METHODSWe used UPLC-Q-TOF-MS to analysis the ingredients and absorbed blood components of FHD. At the same time, the collagen-induced arthritis (CIA) rat model was established to estimate the therapeutic effects on FHD by considering body weight, arthritis score, paw swelling, autonomous movement ability, and synovial microvessel counts. Subsequently, immunofluorescence, immunohistochemistry, and Western blot were employed to detect the anti-angiogenic capacity of FHD in vivo, as well as the levels of apoptosis and autophagy in the synovial tissue. In addition, flow cytometry and Western blot were used to assess the effects of FHD on apoptosis and autophagy in MH7A cells. The effects of FHD on the proliferation and migration of MH7A cells were measured by CCK8 assay, cell migration and, invasion experiments. Finally, a tube formation assay was performed to evaluate the angiogenic capacity of FHD in co-cultures of MH7A cells and HUVEC cells.RESULTSThrough testing of FHD's original formula, a total of 26 active ingredients have been identified, with 17 of them being absorbed into the bloodstream. FHD significantly improved the pathological symptoms and synovial hyperplasia of CIA rats. FHD could suppress the expression of HIF-1α, promote apoptosis in CIA rat synovial tissue, and suppress autophagy and angiogenesis. In vitro experiments showed that serum containing FHD inhibited the proliferation, migration, and invasion of MH7A cells, and also suppressed the expression of autophagy-related proteins while promoting apoptosis. FHD markedly repressed the expression of HIF-1α protein in TNF-α-stimulated MH7A cells and inhibited the tube formation capacity induced by MH7A cells in HUVEC cells.CONCLUSIONSThe study had proven that FHD played an excellent anti-RA role, which may be attributed to its potential mechanism of regulating the balance between autophagy and apoptosis in RA FLS by suppressing the HIF-1α, thus contributing to its anti-angiogenic activities.

01 May 2024·International Immunopharmacology

Unveiling biomarkers and therapeutic targets in IgA nephropathy through large-scale blood transcriptome analysis

Article

Author: Shi, Su-Fang ; Zhang, Yue-Miao ; Gan, Ting ; Zhang, Hong ; Zhou, Xu-Jie ; Li, Yang ; Lv, Ji-Cheng ; Qu, Lu-Xi ; Wang, Yan-Na ; Qi, Yuan-Yuan ; Qu, Shu ; Liu, Li-Jun ; Peng, Yi-Jie

INTRODUCTIONIgA nephropathy (IgAN) is the most prevalent form of glomerulonephritis. Unfortunately, molecular biomarkers for IgAN derived from omics studies are still lacking. This research aims to identify critical genes associated with IgAN through large-scale blood transcriptome analysis.METHODSWe constructed novel blood transcriptome profiles from peripheral blood mononuclear cells (PBMCs) of 53 Chinese IgAN patients and 28 healthy individuals. Our analysis included GO, KEGG, and GSEA for biological pathways. We analyzed immune cell profiles with CIBERSORT and constructed PPI networks with STRING, visualized in Cytoscape. Key differentially expressed genes (DEGs) were identified using CytoHubba and MCODE. We assessed the correlation between gene expressions and clinical data to evaluate clinical significance and identified hub genes through machine learning, validated with an open-access dataset. Potential drugs were explored using the CMap database.RESULTSWe identified 333 DEGs between IgAN patients and healthy controls, mainly related to immune response and inflammation. Key pathways included NK cell mediated cytotoxicity, complement and coagulation cascades, antigen processing, and B cell receptor signaling. Cytoscape revealed 16 clinically significant genes (including KIR2DL1, KIR2DL3, VISIG4, C1QB, and C1QC, associated with sub-phenotype and prognosis). Machine learning identified two hub genes (KLRC1 and C1QB) for a diagnostic model of IgAN with 0.92 accuracy, validated at 1.00 against the GSE125818 dataset. Sirolimus, calcifediol, and efaproxiral were suggested as potential therapeutic agents.CONCLUSIONKey DEGs, particularly VISIG4, KLRC1, and C1QB, emerge as potential specific markers for IgAN, paving the way for future targeted personalized treatment options.

News (Medical) associated with Efaproxiral

09 Nov 2005

·www.biospace.com

Allos Therapeutics, Inc. Reports Third Quarter 2005 Financial Results

WESTMINSTER, Colo., Nov. 9 /PRNewswire-FirstCall/ -- Allos Therapeutics, Inc. today reported financial results for the third quarter of 2005. For the three months ended September 30, 2005, the Company reported a net loss of $4.8 million, or $0.09 per share. This compares to a net loss of $4.6 million, or $0.15 per share, for the three months ended September 30, 2004. For the nine months ended September 30, 2005, the Company reported a net loss of $15.5 million, or $0.36 per share, compared to a net loss of $16.9 million, or $0.54 per share, for the same period last year. Cash, cash equivalents, and investments in marketable securities as of September 30, 2005 amounted to $59.4 million. Product Portfolio Update: EFAPROXYN(TM) (efaproxiral): * ENRICH, the Company's Phase 3 study of the radiation sensitizer EFAPROXYN in patients with brain metastases originating from breast cancer, continues to progress in line with Company expectations. The Company expects to complete patient enrollment in this trial during the second half of 2006 and report preliminary results approximately six months thereafter. * In September 2005, the Company announced the publication of results from its Phase 2 multi-center study of EFAPROXYN in patients with unresectable non-small cell lung cancer (NSCLC) receiving sequential chemoradiotherapy (S-CRT). Results from the study, which were reported in the September 1st edition of the Journal of Clinical Oncology, suggest that the addition of EFAPROXYN to S-CRT may improve survival over S-CRT alone without increasing radiation toxicity rates. * In October 2005, the Company withdrew its European Marketing Authorization Application (MAA) for its investigational radiation sensitizer REVAPROXYN(TM) (efaproxiral, EFAPROXYN(TM) in the United States) for use as an adjunct to whole brain radiation therapy for the treatment of patients with brain metastases originating from breast cancer. The Company believes that the ongoing ENRICH trial, if positive, together with other supporting data, should provide the additional data necessary to support the filing of a new MAA and the future approval of EFAPROXYN for the treatment of brain metastases originating from breast cancer in Europe. * Charles Scott, Ph.D., CBS Squared, is scheduled to present a quality adjusted survival analysis of the Phase 3 REACH study of EFAPROXYN in patients with brain metastases in a poster presentation titled "Improved survival, quality of life and quality-adjusted survival in breast cancer patients treated with efaproxiral + whole brain radiation therapy for brain metastases" at the San Antonio Breast Cancer Symposium on December 10, 2005. PDX (pralatrexate): * Enrollment in a Phase 1/2 study of PDX in patients with relapsed or refractory aggressive lymphoproliferative malignancies continues to progress in line with Company expectations. The Company expects to complete patient enrollment in the Phase 1 portion of this trial in the fourth quarter of 2005. * In January 2005, the Company initiated a Phase 1 dose escalation study of PDX with vitamin B12 and folic acid supplementation in patients with previously treated advanced NSCLC. The Company currently expects to complete patient enrollment in this trial in 2006. RH1: * Enrollment in a Phase 1 dose escalation study of RH1 in patients with advanced solid tumors continues to progress in line with Company expectations. The Company currently expects to complete enrollment in this trial in the fourth quarter of 2005. Sarah Danson, M.D., Department of Medical Oncology, Christie Hospital, is scheduled to report updated clinical and PK/PD data from an on-going Phase 1 study of RH1 in patients with advanced solid tumors in a poster presentation titled "Phase 1 Pharmacokinetic (PD) trial of the bioreductive drug RH1" at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on November 17, 2005. Corporate Highlights: * In October 2005, the only remaining securities class action lawsuit that had been brought against the Company and one of its officers in May 2004 was dismissed with prejudice. In an opinion dated October 20, 2005, the United States District Court for the District of Colorado concluded that the plaintiff's complaint failed to meet the legal pleading requirements applicable to its alleged claims. The plaintiff has until November 19, 2005 to determine whether it will appeal the decision to the U.S. Court of Appeals for the Tenth Circuit. * In July 2005, a shareholder of the Company commenced a stockholder's derivative action in the United States District Court for the District of Colorado against several current and former directors of the Company, naming the Company as a nominal defendant. The factual allegations in the derivative action were substantially the same as the factual allegations in the purported securities class action lawsuit filed in May 2004. On November 2, 2005, the court granted the parties joint motion for voluntary dismissal and dismissed the case without prejudice. Conference Call The Company will host a conference call to review its third quarter results on Wednesday, November 9, 2005, at 11 AM ET. The dial in number for U.S. residents to participate is 877-407-8031. International callers should dial 201-689-8031. Participants should reference the Allos Therapeutics conference call. Conference Call Replay An audio replay of the conference call will be available from 5:30 PM ET on Wednesday, November 9, 2005, until 11:59 PM ET on Wednesday, November 16, 2005. To access the replay, please dial 877-660-6853 (domestic) or 201-612-7415 (international); Replay pass codes (both required for playback): account # 286; conference ID # 175174. Webcast Allos Therapeutics will hold a live webcast of the conference call. The webcast will be available from the homepage and the investors/media section of the Company's web site at and will be archived for 30 days. About Allos Therapeutics, Inc. Allos Therapeutics, Inc. is a biopharmaceutical company focused on developing and commercializing innovative small molecule therapeutics for the treatment of cancer. The Company's lead product candidate, EFAPROXYN(TM) (efaproxiral), is a synthetic small molecule designed to sensitize hypoxic, or oxygen-deprived, tumor tissue during radiation therapy. EFAPROXYN is currently being evaluated as an adjunct to whole brain radiation therapy in a pivotal Phase 3 trial in women with brain metastases originating from breast cancer. The Company's other product candidates are: PDX (pralatrexate), a small molecule chemotherapeutic agent (DHFR inhibitor) currently under investigation as both a single agent and in combination therapy regimens in patients with non-small cell lung cancer and Non-Hodgkin's lymphoma; and RH1, a small molecule chemotherapeutic agent bioactivated by the enzyme DT-diaphorase currently under evaluation in patients with advanced solid tumors. For more information, please visit the Company's web site at: . Safe Harbor Statement This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements concerning our projected timelines for completion of enrollment and announcement of the results of our clinical trials, the potential safety and efficacy of EFAPROXYN for the treatment of patients with NSCLC receiving S-CRT or any other type of cancer, and other statements which are other than statements of historical facts. In some cases, you can identify forward- looking statements by terminology such as "may," "will," "should," "expects," "intends," "plans," anticipates," "believes," "estimates," "predicts," "projects," "potential," "continue," and other similar terminology or the negative of these terms, but their absence does not mean that a particular statement is not forward-looking. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties include, among others: that we may experience difficulties or delays in our clinical trials, whether caused by adverse events, investigative site initiation rates, patient enrollment rates, regulatory issues or other factors; and that clinical trials may not demonstrate the safety and efficacy of our product candidates in their target indications. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K for the year ended December 31, 2004, and in the Company's other periodic reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this presentation, except as required by law. ALLOS THERAPEUTICS, INC. CONDENSED STATEMENTS OF OPERATIONS (in thousands ~ except share and per share information) (unaudited) Three-months ended Nine-months ended September 30, September 30, 2004 2005 2004 2005 Operating expenses: Research and development $2,203 $3,001 $7,638 $7,970 Clinical manufacturing 432 307 2,589 934 Marketing, general and administrative 2,035 2,005 6,989 6,813 Restructuring costs -- -- -- 380 Total operating expenses 4,670 5,313 17,216 16,097 Loss from operations (4,670) (5,313) (17,216) (16,097) Interest and other income, net 116 522 365 1,238 Net loss (4,554) (4,791) (16,851) (14,859) Dividend related to beneficial conversion feature of preferred stock -- -- -- (624) Net loss attributable to common stockholders $(4,554) $(4,791) $(16,851) $(15,483) Basic and diluted net loss per share $(0.15) $(0.09) $(0.54) $(0.36) Weighted average common shares: basic and diluted 31,153,489 55,015,757 31,134,311 43,045,637 ALLOS THERAPEUTICS, INC. CONDENSED BALANCE SHEETS (in thousands) (unaudited) December 31, September 30, 2004 2005 ASSETS Cash, cash equivalents and investments in marketable securities $23,849 $59,426 Other assets 1,344 1,512 Equipment and leasehold improvements, net 980 748 Total assets $26,173 $61,686 Liabilities and Stockholders' Equity Liabilities $2,310 $3,212 Stockholders' equity 23,863 58,474 Total liabilities and stockholders' equity $26,173 $61,686 Allos Therapeutics, Inc. CONTACT: Jennifer Neiman, Manager, Corporate Communications of AllosTherapeutics, Inc., +1-720-540-5227, jneiman@allos.com Web site:

Financial StatementRadiation TherapySmall molecular drugAACR

100 Deals associated with Efaproxiral

External Link

KEGG	Wiki	ATC	Drug Bank
-	Efaproxiral	L01XD06	DB08486

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-small cell lung cancer stage IIIB	Phase 3	Israel	Spectrum Pharmaceuticals, Inc.	01 Nov 2002
Brain metastases	Phase 3	Germany	Spectrum Pharmaceuticals, Inc.	01 Feb 2000
Brain metastases	Phase 3	Canada	Spectrum Pharmaceuticals, Inc.	01 Feb 2000
Brain metastases	Phase 3	France	Spectrum Pharmaceuticals, Inc.	01 Feb 2000
Brain metastases	Phase 3	United States	Spectrum Pharmaceuticals, Inc.	01 Feb 2000
Brain metastases	Phase 3	United Kingdom	Spectrum Pharmaceuticals, Inc.	01 Feb 2000
Brain metastases	Phase 3	Hungary	Spectrum Pharmaceuticals, Inc.	01 Feb 2000
Brain metastases	Phase 3	Australia	Spectrum Pharmaceuticals, Inc.	01 Feb 2000
Brain metastases	Phase 3	Belgium	Spectrum Pharmaceuticals, Inc.	01 Feb 2000
Brain metastases	Phase 3	Italy	Spectrum Pharmaceuticals, Inc.	01 Feb 2000

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


RTOG-94-10 (ASTRO2006)	Phase 2	Locally Advanced Lung Non-Small Cell Carcinoma	402	Efaproxiral + Radiotherapy	fiukaejshv(fkhhbjiylc) = ctjnlfshio wvjqxgklzs (hevofsxccs ) View more	Positive	01 Nov 2006
				Efaproxiral (Sequential arm (STD50))	fiukaejshv(fkhhbjiylc) = vffsageiau wvjqxgklzs (hevofsxccs ) View more
RT-009 (ASTRO2004)	Phase 3	Brain metastases	538	RSR13 plus WBRT and supplemental O2	(opcxkwvxkz) = hhdshyyeuu mabfkdaugl (mcttveiyga )	Positive	01 Sep 2004
ASCO2004	Not Applicable	-	538	RSR13	umzdmsgdkl(yazctiwjnq) = Overall 11% of the patients treated in these studies developed a Serious Adverse Event related to RSR13 abaqhhddlg (vucsgamspk ) View more	-	15 Jul 2004
RT-009 (ASCO2004)	Phase 3	Brain metastases	538	RSR13 and WBRT	voolqlipup(nyswurvevp) = Related SAEs that are part of the RSR13 safety profile occurred in 7% of pts. The most common RSR13-related SAE was hypoxemia (3.4 %), which is dose-dependent and effectively managed with increased supplemental O2. itxyuqjeot (ctjzvbbnmu ) View more	Positive	15 Jul 2004
				RSR13 (efaproxiral) (WBRT)
ASCO2004	Phase 3	Brain metastases	538	RSR13 + O2	(wpvkjioons) = cpdtztmyzc wcyrpctiaq (dwntgqvgxj )	Positive	15 Jul 2004
				RSR13 (efaproxiral) (WBRT + O2)	(wpvkjioons) = obxnjhclas wcyrpctiaq (dwntgqvgxj )
ASTRO2001	Not Applicable	Locally Advanced Lung Non-Small Cell Carcinoma	-	RSR13	zrknahapug(jufoarbzho) = 19% of patients experienced transient RSR-13 induced hypoxemia edgyrzwjuh (ylfeybrvkv ) View more	-	01 Nov 2001

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