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

3,428

Literatures (Medical) associated with Lomustine

01 Mar 2025·Veterinary and Comparative Oncology

Prophylactic Antimicrobials for Prevention of Febrile Neutropenia in Tumour‐Bearing Dogs Treated With Lomustine

Article

Author: Martin, Olya A. ; Zhu, Xiaojuan ; Gumash, Meredith ; Lindley, Stephanie E. S.

ABSTRACTCCNU (1‐[2‐chloroethyl]‐3‐cyclohexyl‐1‐nitrosurea), lomustine, is an oral alkylating agent in the nitrosourea subgroup. The dose‐limiting toxicity of CCNU is neutropenia most frequently documented 7 days after its administration. Use of prophylactic antimicrobials to prevent chemotherapy‐related febrile neutropenia (FN) and its associated morbidity and mortality has been well‐documented in human oncology, but this information is limited in the veterinary literature. The purpose of this multi‐institutional retrospective study was to assess whether antimicrobial prophylaxis reduced the risk of FN approximately 7 days after CCNU administration in tumour‐bearing dogs. A secondary goal was to identify risk factors for fever development in neutropenic dogs. Two hundred dogs were included in the study. One hundred and fifty‐three dogs (76.5%) were neutropenic at the first post‐CCNU recheck. One hundred and six (69.3%) dogs received prophylactic antimicrobials and 47 (30.7%) did not. Of the 106 dogs on prophylactic antimicrobials, 8 (7.5%) developed FN. Of the 47 dogs in the no‐prophylactic antimicrobials group, 4 (8.5%) developed FN. Use of prophylactic antimicrobials did not reduce the risk of development of FN (p = 0.84). Older age (> 9 y), lower weight and body surface area, and pre‐treatment with chemotherapy or radiation therapy were significantly associated with development of FN (p = 0.009, p = 0.023, p = 0.015 and p = 0.01). Patients with a lower absolute neutrophil count, and a higher VCOG‐CTCAE v2 neutropenia grade were also at an increased risk of developing FN (p = 0.01, p < 0.001). Additional studies may help establish guidelines for antimicrobial prophylaxis in dogs treated with CCNU, especially for those at high‐risk for FN.

01 Mar 2025·NMR in Biomedicine

Extension of T₂ Hyperintense Areas in Patients With a Glioma: A Comparison Between High‐Quality 7 T MRI and Clinical Scans

Article

Author: Kuhn‐Keller, Jasmin A. ; Cornelissen, Ivo ; van Osch, Matthias J. P. ; Dirven, Linda ; de Bresser, Jeroen ; Schmitz‐Abecassis, Bárbara ; Jacobs, Robin ; Koekkoek, Johan A. F. ; Taphoorn, Martin

ABSTRACTGliomas are highly heterogeneous and often include a nonenhancing component that is hyperintense on T2 weighted MRI. This can often not be distinguished from secondary gliosis and surrounding edema. We hypothesized that the extent of these T2 hyperintense areas can more accurately be determined on high‐quality 7 T MRI scans. We investigated the extension, volume, and complexity (shape) of T2 hyperintense areas in patients with glioma on high‐quality 7 T MRI scans compared to clinical MRI scans. T2 hyperintense areas of 28 patients were visually compared and manually segmented on 7 T MRI and corresponding clinical (1.5 T/3 T) MRI scans, and the volume and shape markers were calculated and subsequently compared between scans. We showed extension of the T2 hyperintense areas via the corpus callosum to the opposite hemisphere in four patients on the 7 T scans that was not visible on the clinical scan. Furthermore, we found a significantly larger volume of the T2 hyperintense areas on the 7 T scans compared with the clinical scans (7 T scans: 28 mL [12.5–59.1]; clinical scans: 11.9 mL [11.8–56.6]; p = 0.01). We also found a higher complexity of the T2 hyperintense areas on the 7 T scans compared with the clinical scans (convexity, solidity, concavity index and fractal dimension [p < 0.001]). Our study suggests that high‐quality 7 T MRI scans may show more detail on the exact extension, size, and complexity of the T2 hyperintense areas in patients with a glioma. This information could aid in more accurate planning of treatment, such as surgery and radiotherapy.

10 Feb 2025·Neuro-Oncology

Quantitative assessment of residual tumor is a strong and independent predictor of survival in methylated glioblastoma following radiochemotherapy with lomustine/temozolomide

Article

Author: Hattingen, Elke ; Kowalski, Thomas ; Grauer, Oliver ; Weller, Johannes ; Schneider-Rothhaar, Javen Lennard ; Vatter, Hartmut ; Duffy, Cathrina ; Stummer, Walter ; Böhm, Laura ; Galldiks, Norbert ; Seidel, Clemens ; Schäfer, Niklas ; Paech, Daniel ; Tzaridis, Theophilos ; Glas, Martin ; Gkika, Eleni ; Steinbach, Joachim Peter ; Hau, Peter ; Schaub, Christina ; Radbruch, Alexander ; Schneider, Matthias ; Goldbrunner, Roland ; Krex, Dietmar ; Zeiner, Pia Susan ; Herrlinger, Ulrich ; Zeyen, Thomas ; Tabatabai, Ghazaleh ; Potthoff, Anna-Laura ; Nitsch, Louisa

AbstractBackgroundMaximum tumor resection improves overall survival (OS) in patients with glioblastoma. The extent of resection (EOR) is historically dichotomized. The response assessment in neuro-oncology (RANO) resects group recently proposed criteria for volumetry-based EOR assessment in patients that were treated according to Stupp´s protocol. The purpose of this study was (1) to investigate the prognostic value of EOR in patients receiving combined chemotherapy with lomustine (CCNU)/temozolomide (TMZ), and (2) to analyze the prognostic performance of binary EOR assessment compared to volumetric assessment.MethodsSeventy-eight patients with newly diagnosed MGMT-methylated GBM undergoing tumor resection followed by radiochemotherapy with CCNU/TMZ were included in this study. Residual contrast-enhancing (CE) tumor volume after the first resection was measured and its influence on OS and progression-free survival was analyzed using uni- and multivariable Cox regression analysis as well as two-sided log-rank test. Patients were divided into residual tumor volume (RTV) ≤1 cm³, >1–≤5 cm³, and >5 cm³ following the proposed criteria of the RANO resect group.ResultsProlonged OS was associated with age <60 years, low RTV, and gross total resection. RTV had a superior prognostic value compared to binary EOR assessment. Patients with total or near total resection of CE tumor (≤ 1 cm³ RTV) showed prolonged OS (median 54.4 months, 95% CI: 46.94–not reached), with a 5-year survival rate of 49%.ConclusionsLow RTV is associated with increased survival in glioblastoma patients undergoing radiochemotherapy with CCNU/TMZ. This study demonstrates the applicability of the recently proposed RANO resect criteria in this subgroup of patients.

News (Medical) associated with Lomustine

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

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

10 Jul 2024

·www.fiercebiotech.com

Kazia prunes failed brain cancer trial data set to manufacture path to FDA

Kazia Therapeutics saw the survival signal after pruning the control cohort. Kazia Therapeutics has found a way to try to salvage a win from a failed late-phase brain cancer trial. By removing part of the control arm, the biotech has emerged with survival data it will share with the FDA to see whether a path to accelerated approval has opened up. The data come from a platform study sponsored by the Global Coalition for Adaptive Research. The trial has enrolled patients with newly diagnosed and recurrent glioblastoma, a hard-to-treat brain cancer, to receive molecules developed by companies including Bayer and Biohaven. The design allows researchers to compare a revolving cast of candidates to a standard-of-care control arm in a single study. In August 2022, Kazia said its contribution to the study, a PI3K/mTOR inhibitor discovered by Genentech, failed to meet the threshold for advancing to the next stage of the trial. Now, Kazia has shared the data behind the failure—and made the case that there is a positive story to tell. Investigators enrolled two subgroups of patients to receive Kazia’s candidate paxalisib. The molecule was numerically worse than the control treatment, lomustine, in patients with recurrent disease, achieving a median overall survival (OS) of 8.05 months compared to 9.69 months for the standard of care. That part of the study featured 213 patients, split roughly evenly between paxalisib and the control. Kazia focused its discussion of the data on the other subgroup, which enrolled newly diagnosed patients with a form of the disease that is less likely to respond to the chemotherapy drug temozolomide. In that subgroup, Kazia reported a median OS of 14.77 months in 54 recipients of paxalisib. The result was barely better than the 13.84 months seen in the temozolomide control cohort. However, Kazia found a subset of the control arm that painted a better picture of paxalisib. Because paxalisib was added to the platform trial around 18 months after the study began, roughly one-third of the 75 patients in the newly diagnosed control arm were enrolled before dosing of Kazia’s drug candidate started. Limiting the control arm to the 46 patients who were enrolled concurrently to Kazia’s prospect resulted in a median OS of 11.89 months. Kazia CEO John Friend, M.D., hailed the result as a “3.8 month improvement in overall survival, an approximate 33% improvement,” in a statement. The biotech now plans to discuss the data with the FDA to “determine if a potential path to accelerated approval is appropriate for paxalisib.” Kazia’s share price rose around 70% in premarket trading, but that jump only brought it up to 33 cents.

Clinical ResultAccelerated Approval

100 Deals associated with Lomustine

External Link

KEGG	Wiki	ATC	Drug Bank
D00363	Lomustine	L01AD02	DB01206

R&D Status

Approved

10 top approved records.

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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

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioma	Discovery	United States	Istari Oncology, Inc.Startup	01 Jun 2017

Clinical Result

Indication

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CTRI/2020/07/026696 (VAMANA, ASCO2024) Manual	Phase 2	Glioblastoma	46	bevacizumab+CCNU	(hxrosavwpf) = yfqomkemwp whdfeopyli (wtdjsyqfqg, 5.474 - 6.793) View more	Positive	02 Jun 2024
EORTC 26101 (SNO2022)	Phase 2/3	Recurrent Glioblastoma	-	Lomustine alone	evydayrqad(neatpzrxvb) = Thrombocytopenia represents the main cause of stopping chemotherapy for toxicity during the treatment of glioblastoma euuqapplhn (wiqrrbbjlm ) View more	Negative	14 Nov 2022
				Lomustine plus bevacizumab
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))	(vnqejrhegb) = kjfoluhwbo prdnwvdnfk (qsqqphnzsu, xrjeabsgmg - gjzilsbncp) View more	-	10 Oct 2022
				laboratory biomarker analysis+etoposide+cyclophosphamide+lomustine+procarbazine hydrochloride (Arm II (Oral Chemotherapy))	(vnqejrhegb) = taalyomrxd prdnwvdnfk (qsqqphnzsu, dhovsathby - bjmhnnaziv) View more
CeTeG/NOA-09 (EANO2022)	Phase 3	First line	70	Lomustine plus Temozolomide	fucwydowwa(kmabulrjgo) = olgjwjtokz cfgknxcuvd (mnsqgtndwb ) View more	Positive	05 Sep 2022
				lomustine (TTFields treatment for 8 weeks or longer)	oyvgaqwzpy(qapziwlhne) = tbuowgxkgr upbamjkhqt (pyynyxskrx )
NCT03022578 (CTgov)	Phase 2	Recurrent Glioblastoma	7	Laser Interstitial Thermal Therapy+Lomustine	padjjmutpp(mbuwhncbbu) = xwdfdsygwp ehkdixheux (xdxxhfrxat, qshdtrckua - ykfqkwucbv) View more	-	10 Aug 2022
NCT03678883 (Pubmed) Manual	Phase 1/2	Neoplasms \| Malignant glioma of brain	18	Lomustine+Elraglusib	(gpeympqvod) = mild vision changes 50%, infusion reactions 22% pbnpbovaba (isjnfhcaaa ) View more	Positive	07 Feb 2022
CeTeG/NOA-09 (SNO2021)	Not Applicable	Glioblastoma MGMT promotor-methylated \| RTK I/MES subgroup	98	Lomustine (RTK I/MES subgroup)	(lgvbnlrtwi) = qkdzjdqjtd gfzsjacqfy (ngkoxkhqiq )	Positive	12 Nov 2021
				Lomustine (RTK II subgroup)	(lgvbnlrtwi) = mjqmxtaret gfzsjacqfy (ngkoxkhqiq )
NCT03678883 (ACTUATE 1801, SNO2021)	Phase 1/2	Glioma IDH \| 1p19q \| MGMT ... View more	18	9-ING-41 monotherapy	vbzkdvtvap(pfawkvbcvw) = wuzcwjdfne dvcijfauqe (pjhwjtzhku ) View more	Positive	12 Nov 2021
				9-ING-41 + Lomustine	kpiflaxtzz(rzqtyubijv) = vlysaoulec fchhrzrcxk (demlosalfw ) View more
P14.58 (EANO2021)	Not Applicable	Recurrent Glioblastoma MGMT promotor methylation \| IDH mutation	236	Lomustine	ioufqpwgwf(hbzldtccea) = iymptnegju ndqsatospl (ielatlsnsj ) View more	Negative	09 Sep 2021
				Fotemustine	ioufqpwgwf(hbzldtccea) = hrsxnogkke ndqsatospl (ielatlsnsj ) View more
NCT02076152 (CTgov)	Not Applicable	Recurrent Glioblastoma	11	FMISO PET+Bevacizumab (FMISO PET & MRI Group 1)	rrlzswvkbf(bbtumfuylh) = pbnzvjrkhr ucnqhazyjb (ziibingxoj, parbkmxlxh - sxypsyrcfm) View more	-	30 Jul 2021
				FMISO PET+CCNU+Bevacizumab (FMISO PET & MRI Group 2)	rrlzswvkbf(bbtumfuylh) = osewyimhsh ucnqhazyjb (ziibingxoj, wwishyqfwk - weyatuxdmy) View more

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