Phase III Trial of Temozolomide/Lomustine (TMZ/LOM) Combination Therapy vs. Standard TMZ Therapy for Newly Diagnosed MGMT Promoter Methylated Glioblastoma (IDHwt) Patients +/- Tumor Treating Fields (Optune)

Background: Glioblastoma (GBM) is notoriously difficult to treat, with current therapies often extending life by only a few months. The standard treatment involves surgery followed by radiation and chemotherapy with Temozolomide (TMZ). The efficacy of TMZ, however, is significantly enhanced when the tumor's o6-methylguanine-DNA-methyltransferase (MGMT) gene is methylated. Recent studies, such as the NOA-09 trial, have suggested that adding Lomustine (LOM) to TMZ could improve outcomes for patients with this specific tumor profile.
Hypothesis: The investigators hypothesize that the addition of LOM to the TMZ regimen will lead to significantly improved survival rates among patients with newly diagnosed glioblastoma who have a methylated MGMT promoter compared to those receiving only TMZ.
Treatment Plans: The study will randomly assign participants to two groups:
* Control Group: Standard treatment with TMZ during and after radiation therapy.
* Experimental Group: TMZ combined with LOM, starting on the first day of radiation therapy.
Outcome Measures: The primary outcome measure will be survival. Other outcomes will include progression-free survival (time from randomization until tumor progression or death), safety profiles (adverse effects of the treatments), and quality of life measures as well as neurocognitive outcomes.

Start Date01 Dec 2024

Sponsor / Collaborator

Region Västra Götaland

[+11]

NCT06336291

/ RecruitingPhase 2

A Dose Optimization Study for L19TNF in Combination with Lomustine in Patients with Glioblastoma At Progression or Recurrence

The trial aims to collect safety, efficacy, exposure, dose- response, pharmacokinetic and pharmacodynamic information of the combination of L19TNF and lomustine at different dose levels in patients with Glioblastoma at progression or recurrence

Start Date22 May 2024

Sponsor / Collaborator

Philogen SpA

NCT05904119

/ RecruitingPhase 3IIT

Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study

Despite comprehensive multimodal treatment of newly diagnosed glioblastoma, almost all patients suffer from tumour relapse. Currently, no standard of care exists to treat these tumour relapses. Treatment options include repeated surgery (if feasible), systemic therapy (bevacizumab, lomustine, temozolomide re-challenge), reirradiation and best supportive care. Currently, the superiority of combined chemoradiation versus chemotherapy alone remains unproven. Given that lomustine is the standard chemotherapeutic agent for the treatment of recurrent glioblastoma in Europe and the unclear efficacy of reirradiation, we want to explore whether combining lomustine and reirradiation may be a better treatment than lomustine alone. The results of the prospective randomized trial proposed here should demonstrate a significant improvement in overall survival when lomustine is combined with reirradiation in patients with recurrent glioblastoma compared to lomustine alone without adversely affecting quality of survival. The trial will be stopped based on overall survival in a preplanned futility and efficacy interim analysis.

Start Date15 Mar 2024

Sponsor / Collaborator

Eortc

[+1]

100 Clinical Results associated with Lomustine

100 Translational Medicine associated with Lomustine

100 Patents (Medical) associated with Lomustine

3,426

Literatures (Medical) associated with Lomustine

04 May 2025·TOXICOLOGY MECHANISMS AND METHODS

Differences in metabolite genotoxicity test results of rat liver S9 microsomes treated with various microsomal enzyme inducers

Article

Author: Shinozawa, Tadahiro ; Matsui, Toshikatsu ; Hashimoto, Kiyohiro ; Igaki, Shigeru

The rat S9 microsome fraction is commonly used to assess compound metabolite formation during in vitro genotoxicity assessments. However, methods using S9 have not been standardized for genotoxicity studies, and different experimental methods are used at various facilities. Therefore, this study investigated whether the differences between the two experimental conditions (1) S9 inducers, phenobarbital + beta-naphthoflavones vs. Aroclor 1254 and (2) the plate incubation vs. preincubation method) in the micro-Ames test would affect the results. Nitrosamine and in-house genotoxicity-positive compounds were used with benzopyrene and 2-aminofluorene as positive control compounds. No differences were observed in the genotoxicity results in the groups treated with the positive control. However, the S9 fraction induced by Aroclor 1254 showed higher cytochrome P450 activity than the fraction induced by phenobarbital and beta-naphthoflavone. The incubation method also affected the results; the nitrosamine compounds showed different genotoxicity activity between the plate incorporation method and preincubation method. In-house aminomethyl quinoline compounds also showed different results depending on the S9 type. These results suggest that different inducers and methods induce various metabolic enzyme activities, which may lead to differences in genotoxicity through distinct metabolite production.

01 May 2025·JOURNAL OF CONTROLLED RELEASE

Preclinical evaluation of several polymeric micelles identifies Soluplus®-docetaxel as the most effective candidate in multiple glioblastoma models

Article

Author: Alcina, Àngels ; Sarmento, Bruno ; Rafael, Diana ; Ferrer-Costa, Roser ; Fischer-Albiol, Narine ; Schwartz, Simó ; Mancilla, Sandra ; Pumarola, Alexandra ; Herrero, Raquel ; Abasolo, Ibane ; García, Belén ; Sánchez-Gómez, Pilar ; Díaz-Riascos, Zamira V ; Torroglosa, Natalia ; German-Cortés, Júlia ; Sabaté, Sofia ; Martins, Cláudia ; Andrade, Fernanda ; Campos-Moreno, Sofia ; Llaguno-Munive, Monserrat

Glioblastoma multiforme (GBM) is one of the most lethal cancers, with limited treatment options due to the blood-brain barrier (BBB), systemic toxicity, and treatment resistance. Nanomedicine offers potential solutions to these challenges. This study explores Pluronic® F127 and Soluplus®-based micelles as carriers for Lomustine, Gefitinib, and Docetaxel to determine the optimal system for GBM therapy. Micelles were physicochemically characterized and biologically validated using U87-MG and U251-MG GBM cell lines in 2D and 3D models, assessing internalization, safety, and therapeutic efficacy. Soluplus® micelles (SM) showed favorable properties for intravenous administration, including low polydispersity, efficient drug release in the tumoral microenvironment, minimal cell toxicity, and a BBB-crossing rate of 15 %. Among the drugs tested, Docetaxel showed the lowest IC₅₀ values in both 2D cell models and demonstrated superior efficacy in 3D cultures when delivered by SM. Molecular analysis confirmed that SM-D impacts key GBM-related pathways, affecting markers like E-cadherin, EPCAM, L1CAM, or EGFR. In vivo, SM-D significantly reduced tumor mass and cancer cell density, showing a favorable safety profile compared to free Docetaxel, as evidenced by reduced weight loss and histological assessments. Overall, SM-D stands out as the most promising approach for GBM treatment, supporting the potential of nanomedicine in overcoming the barriers to effective glioblastoma therapy.

01 Apr 2025·VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE

Drug-Induced Liver Injury

Review

Author: Reinhart, Jennifer M

Drug-induced liver injury (DILI) is an underrecognized cause of hepatic disease in dogs and cats. Successful identification of cases requires an initial suspicion by the practitioner, a thorough drug exposure history, and knowledge of the toxic potential for common veterinary drugs. This article reviews the pathogenesis, classification, and diagnosis of DILI in small animals. It also discusses the clinical presentation, prevalence, and outcomes of DILI for several drugs important in veterinary medicine including azathioprine, azole antifungals, carprofen, diazepam, doxycycline, lomustine, methimazole, phenobarbital, rifampin, sulfonamide antibiotics, and zonisamide, as well as the toxic potential for nutraceuticals and herbal preparations.

News (Medical) associated with Lomustine

22 Apr 2025

·www.businesswire.com

Carthera Reaches Recruitment Milestone in SONOBIRD Pivotal Trial for Recurrent Glioblastoma

PARIS--(BUSINESS WIRE)--Carthera, developer of the revolutionary SonoCloud® medical device, today announces it has enrolled the first 100 patients in its SONOBIRD pivotal trial for the treatment of recurrent glioblastoma. A spin-off of Sorbonne University founded by noted neurosurgeon Prof. Alexandre Carpentier, Carthera reaches this milestone as it prepares to conduct the largest clinical trial ever using ultrasound for the temporary opening of the blood-brain-barrier (BBB) in patients with recurrent glioblastoma. Nearly all 40 participating sites across Europe and the U.S. are now active. Carthera anticipates that recruitment will continue swiftly to reach the 560 patients planned for the study. The trial (NCT05902169) is the world’s first randomized, multicentric, two-arm pivotal trial of BBB opening prior to chemotherapy injection in recurrent glioblastoma patients. Notably, the trial makes use of the SonoCloud, an innovative ultrasound-based medical device developed by Carthera to treat a wide range of brain disorders. Specifically, the trial compares the use of SonoCloud combined with carboplatin versus standard therapies in patients with a first recurrence of glioblastoma. “It has been a privilege to offer this trial to patients with recurrent glioblastoma. The underlying concept is highly promising, device implantation has proceeded smoothly and patients have shown strong interest in participating,” said Dr. Brian Gill, assistant professor of neurosurgery at Columbia University Irving Medical Center in New York. “We desperately need new treatments for patients with recurrent glioblastoma. SonoCloud has the potential to transform our ability to deliver a high dose of therapeutics to the brain,” said Dr. Marjolein Geurts, neuro‐oncologist at Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. To date, more than 550 SonoCloud treatments have been performed worldwide, confirming Carthera’s position as a leader in the field of ultrasound-based BBB opening, as well as the growing interest in SonoCloud as a potentially viable new treatment option for patients with recurrent glioblastoma. “Our progress in recruiting patients reflects the engagement and strong support from our clinical sites, and from the neuro-oncology and surgery community, in advancing innovative therapies,” said Carole Desseaux, chief clinical officer at Carthera. “We are very grateful for the commitment and enthusiasm of the patients and clinicians who are taking part in this trial.” “Achieving this milestone is an important step in introducing our SonoCloud device to the large patient population urgently in need of solutions to improve treatment outcomes,” said Frederic Sottilini, CEO of Carthera. “With its breakthrough device and orphan drug designations, Carthera remains committed to transforming glioblastoma treatment and to acquiring market access for its groundbreaking technology.” Initiated in February 2024, the registrational study aims to enroll a total of 560 US and EU patients within two years, with a view to obtaining marketing authorization. The first interim analysis of the clinical data will be available soon. About the SONOBIRD trial The open-label, comparative, randomized, multicenter, two-arm clinical trial with a 1:1 ratio aims to evaluate overall survival in patients undergoing carboplatin chemotherapy and treated with the SonoCloud system to open the Blood-Brain Barrier (BBB). This is compared to the medical consensus recommended regimens (lomustine or temozolomide). The trial also evaluates the effectiveness of the SonoCloud and carboplatin treatment in delaying or slowing tumor growth. The SONOBIRD trial follows on from the SC9-GBM-01 trial, which demonstrated the feasibility and the safety profile of SonoCloud, as well as the potential of carboplatin tested as a monotherapy in combination with BBB opening. About SonoCloud SonoCloud® is an innovative medical device developed by Carthera. It emits ultrasound to temporarily increase the permeability of the blood vessels in the brain to improve the delivery of therapeutic molecules. Invented by Prof. Alexandre Carpentier and developed in collaboration with the Laboratory of Therapeutic Applications of Ultrasound (Laboratoire Thérapie et Applications Ultrasonores, LabTAU, INSERM) in Lyon, France, SonoCloud is an implant inserted into the skull and activated prior to injection of a therapeutic agent. Several minutes of low-intensity ultrasound opens the blood-brain barrier for six hours and increases the concentration of therapeutic molecules in the brain. This ultrasound-induced opening of the blood-brain barrier is a world-first. It offers a new treatment option for a wide range of indications, including brain tumors and Alzheimer’s disease. SonoCloud is an investigational product, the device has not yet received EMA or FDA approval. About Carthera Carthera is a clinical-stage medtech company focused on developing innovative ultrasound-based medical devices to treat a wide range of brain disorders. The company is a spin-off from AP-HP Paris and Sorbonne University. Carthera leverages the inventions of Prof. Alexandre Carpentier, head neurosurgeon at AP-HP Sorbonne university, who has achieved worldwide recognition for his innovative developments in treating brain disorders. Carthera is developing SonoCloud®, an intracranial implant that temporarily opens the blood-brain barrier. The device is currently in clinical trials in Europe and the United States. It received FDA Breakthrough Device Designation in 2022, and FDA/EMA Orphan Drug Designation in 2023 for carboplatin when used with SonoCloud. Founded in 2010 by Prof. Alexandre Carpentier, run by CEO Frederic Sottilini and chaired by Oern Stuge, MD, Carthera has offices in France (Lyon and Paris) and a subsidiary in Boston, Massachusetts. Since its inception, the technical and clinical development of SonoCloud has received support from the National Research Agency (ANR), the French public investment bank (Bpifrance), the National Institutes of Health (NIH) and the European Innovation Council (EIC). Additional information is available at www.carthera.eu.

Clinical StudyOrphan Drug

11 Jul 2024

·www.biospace.com

Kazia Offers Secondary OS Data to Build FDA Case for Glioblastoma Drug

Pictured: 3D illustration of a tumor on a brain/iStock, wildpixel Kazia Therapeutics on Wednesday unveiled additional data from the Phase II/III GBM-AGILE study, picking out secondary efficacy signals as it eyes an FDA accelerated approval pathway for its investigational glioblastoma treatment paxalisib. GBM-AGILE is a large global study designed to test several investigational glioblastoma treatments versus current standard of care. In the case of paxalisib, the study used chemotherapy with temozolomide for newly diagnosed patients and with lomustine for those with recurrent disease. The primary outcome of interest was overall survival (OS). Paxalisib showed no signs of efficacy in the recurrent disease setting. Median OS in treated patients was 8.05 months, which was nearly two months shorter than the 9.69-month median OS in comparators treated with lomustine. The Australian biotech is currently conducting deeper analysis of these data “to elucidate potential signs for further consideration.” Kazia is focused on the subset of patients who were newly diagnosed with glioblastoma. In this population, paxalisib led to a median OS of 14.77 months, slightly longer than that in temozolomide counterparts, who survived for a median of 13.84 months. The biotech further zoomed in on a smaller slice of control patients who were enrolled into GBM-AGILE concurrently with paxalisib’s inclusion into the study. In this concurrent population, median OS for paxalisib grew to 15.54 months while that for comparators dipped to 11.89 months. Kazia CEO John Friend pointed to this survival difference, saying that the biotech is “excited to have shown a 3.8-month improvement in overall survival, an approximate 33% improvement, for newly diagnosed unmethylated patients with GBM compared to the concurrent standard-of-care arm.” “Having comparable [OS] data across two independent studies in a compelling outcome in this difficult to treat population,” Friend noted, adding that the biotech will bring these findings to the FDA to discuss “possible approaches” to an accelerated approval for paxalisib. The market reacted favorably to Kazia’s readout, with its stocks surging 142% on Wednesday, according to SeekingAlpha. Initially invented by Genentech, paxalisib works by inhibiting the action of PI3K, a key player in cell growth and division which are highly dysregulated in several cancers. Unlike most other PI3K blockers, paxalisib can cross the blood-brain barrier making it a promising candidate for malignancies of the central nervous system. In August 2022, Kazia reported that paxalisib failed to reach the pre-defined criteria for moving to the second phase of GBM-AGILE. However, at the time, the biotech was still blinded to the study’s results and could not fully understand the failure. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Accelerated ApprovalClinical ResultDrug Approval

11 Jul 2024

·www.biospace.com

Kazia Offers Secondary OS Data to Build FDA Case for Glioblastoma Drug

3D illustration of a tumor on a brain iStock, wildpixel Kazia Therapeutics is eyeing an FDA accelerated approval pathway for its investigational glioblastoma drug paxalisib, with Wednesday’s release of secondary overall survival data from a Phase II/III trial. Kazia Therapeutics on Wednesday unveiled additional data from the Phase II/III GBM-AGILE study, picking out secondary efficacy signals as it eyes an FDA accelerated approval pathway for its investigational glioblastoma treatment paxalisib. GBM-AGILE is a large global study designed to test several investigational glioblastoma treatments versus current standard of care. In the case of paxalisib, the study used chemotherapy with temozolomide for newly diagnosed patients and with lomustine for those with recurrent disease. The primary outcome of interest was overall survival (OS). Paxalisib showed no signs of efficacy in the recurrent disease setting. Median OS in treated patients was 8.05 months, which was nearly two months shorter than the 9.69-month median OS in comparators treated with lomustine. The Australian biotech is currently conducting deeper analysis of these data “to elucidate potential signs for further consideration.” Kazia is focused on the subset of patients who were newly diagnosed with glioblastoma. In this population, paxalisib led to a median OS of 14.77 months, slightly longer than that in temozolomide counterparts, who survived for a median of 13.84 months. The biotech further zoomed in on a smaller slice of control patients who were enrolled into GBM-AGILE concurrently with paxalisib’s inclusion into the study. In this concurrent population, median OS for paxalisib grew to 15.54 months while that for comparators dipped to 11.89 months. Kazia CEO John Friend pointed to this survival difference, saying that the biotech is “excited to have shown a 3.8-month improvement in overall survival, an approximate 33% improvement, for newly diagnosed unmethylated patients with GBM compared to the concurrent standard-of-care arm.” “Having comparable [OS] data across two independent studies in a compelling outcome in this difficult to treat population,” Friend noted, adding that the biotech will bring these findings to the FDA to discuss “possible approaches” to an accelerated approval for paxalisib. The market reacted favorably to Kazia’s readout, with its stocks surging 142% on Wednesday, according to SeekingAlpha . Initially invented by Genentech, paxalisib works by inhibiting the action of PI3K, a key player in cell growth and division which are highly dysregulated in several cancers. Unlike most other PI3K blockers, paxalisib can cross the blood-brain barrier making it a promising candidate for malignancies of the central nervous system. In August 2022, Kazia reported that paxalisib failed to reach the pre-defined criteria for moving to the second phase of GBM-AGILE. However, at the time, the biotech was still blinded to the study’s results and could not fully understand the failure.

Clinical ResultAccelerated ApprovalDrug Approval

100 Deals associated with Lomustine

External Link

KEGG	Wiki	ATC	Drug Bank
D00363	Lomustine	L01AD02	DB01206

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Bronchogenic Carcinoma	China	Nanjing Pharmaceutical Factory	01 Jan 1982
Glioma	China	Nanjing Pharmaceutical Factory	01 Jan 1982
Lymphoma	China	Nanjing Pharmaceutical Factory	01 Jan 1982
Rectal Cancer	China	Nanjing Pharmaceutical Factory	01 Jan 1982
Stomach Cancer	China	Nanjing Pharmaceutical Factory	01 Jan 1982
Brain Cancer	United States	Corden Pharma Latina SpA	04 Aug 1976
Hodgkin's Lymphoma	United States	Corden Pharma Latina SpA	04 Aug 1976

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CeTeG/NOA-09 (EANO2024)	Not Applicable	Glioblastoma MGMT-methylated \| IDH-wildtype	17	CCNU/TMZ	rcnezpmdkf(bohgobblnh) = fykjelgjan sfzcpdxbmm (tihafynhgl, 17.6 - not reached) View more	Positive	17 Oct 2024
CeTeG/NOA-09 (EANO2024)	Phase 3	Glioblastoma	31	Lomustine-Temozolomide Chemotherapy + Radiotherapy	zacpykywip(plcyfjcgdr) = mvbkwachpf knxuurnanv (whdoxlhuzt )	Positive	17 Oct 2024
CTRI/2020/07/026696 (VAMANA, ASCO2024) Manual	Phase 2	Glioblastoma	46	bevacizumab+CCNU	ifkuhxxhmc(iwvppqolsi) = llfzdvftty jlutvzxydh (yyipjyegpi, 5.474 - 6.793) View more	Positive	02 Jun 2024
EORTC 26101 (SNO2022)	Phase 2/3	Recurrent Glioblastoma	-	Lomustine alone	hhzrxctgyr(ozmrgnphok) = Thrombocytopenia represents the main cause of stopping chemotherapy for toxicity during the treatment of glioblastoma liqrzukupc (suywxhkauc ) View more	Negative	14 Nov 2022
				Lomustine plus bevacizumab
PROTECT (SNO2022)	Not Applicable	Low grade glioma Adjuvant 1p/19q co-deletion	20	Procarbazine, Lomustine, Vincristine (PCV)	yxcfdecfzi(bbnjdswnel) = ttcozrormg hsainoffsu (hmsnpklnmu ) View more	Negative	14 Nov 2022
				Temozolomide (TMZ)	yxcfdecfzi(bbnjdswnel) = nguaguibdr hsainoffsu (hmsnpklnmu ) View more
BIOM-12 (SNO2022)	Not Applicable	Glioblastoma, IDH-Wildtype Third line MGMT-methylated \| IDH-wildtype \| TERT mutant ... View more	-	CCNU/TMZ combination therapy	xblomztgaq(dxzkhgxakl) = qmfvzehalr udcmkzbbjw (ltbcqmwqgm )	-	14 Nov 2022
NCT01775475 (CTgov)	Phase 2	AIDS-Related Lymphoma \| AIDS-Related Diffuse Large Cell Lymphoma \| Immunoblastic Large-Cell Lymphoma	7	laboratory biomarker analysis+cyclophosphamide+prednisone+doxorubicin hydrochloride+vincristine sulfate (Arm I (CHOP))	fbhhoqiaiw = ouuaugvdib gafyswfaqr (uksygajorf, kycbttcdjb - rojpdkopdx) View more	-	10 Oct 2022
				laboratory biomarker analysis+etoposide+cyclophosphamide+lomustine+procarbazine hydrochloride (Arm II (Oral Chemotherapy))	fbhhoqiaiw = qnoafpjgdn gafyswfaqr (uksygajorf, tsyyurfkxq - cjqjowlqny) View more
CeTeG/NOA-09 (EANO2022)	Phase 3	First line	70	Lomustine plus Temozolomide	hcvgotyhrd(iixfqtgpbd) = rjwtqfrsof xfqmspyyoo (murjbdpeia ) View more	Positive	05 Sep 2022
				lomustine (TTFields treatment for 8 weeks or longer)	ccnwrfqtky(hzeqdgypkv) = hwqlqyinms vevsfxypef (nfzmfpxfcf )
NCT03022578 (CTgov)	Phase 2	Recurrent Glioblastoma	7	Laser Interstitial Thermal Therapy+Lomustine	ixbyzwiyxc = axcewdiqch wasevwpped (tdnzffpnov, gjmpnmakgc - wjmtowfhpu) View more	-	10 Aug 2022
NCT00002840 \| NCT00002569 (EORTC 26951 and RTOG 9402, Pubmed)	Phase 3	Oligodendroglioma Adjuvant	299	Radiotherapy+PCV	byluoqbang(vlokotebab) = fxcnkjtfzq whshwwnsmr (wclrtelgzu ) View more	Positive	22 Jun 2022
				Radiotherapy	byluoqbang(vlokotebab) = bkzavghvud whshwwnsmr (wclrtelgzu ) View more

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