Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Bortezomib

Antineoplastic Agents, Alkylating

Alkylating Agents

Botezomib 1.3 mg/m2 administered IV on days 1, 4, 7, during each 4-week chemotherapy cycle with per oral Temozolomide at three dose levels: 150 mg/m2, 175 mg/m2 and 200mg/m2 5 days/week every 4 weeks starting on day 3.

In the Phase IB of the study the following dose escalation of TMZ will be performed: The first cohort of 3 patients will receive 150 mg/m2 of IMP (TMZ) for 5 days q4w. If one patient in this cohort develops a dose limiting toxicity, another cohort of 3 patients will be treated at the same dose level until 2 or more patients in the group of 3-6 develop DLT.

Bortezomib and Temozolomide Phase IB

The patientes will be treated with the maximum recommended starting dose of Temozolomide and Bortezomib established in the IB phase of the study

Bortezomib and Temozolomide Phase II

Dorota Goplen, MD, PhD

Martha E Chekenya, PhD, Dr. Philos

Jorunn Brekke, MD

Petter Brandal, MD

This phase IB/II trial is designed to investigate the safety and survival benefits for patients with recurrent grade-4 with unmethylated MGMT promoter treated with Bortezomib and Temozolomide in a specific schedule.

Patients harbouring tumours with functional O6 methylguanine DNA methyltransferase (MGMT) DNA repair enzyme efficiently repair the DNA damage inflicted by Temozolomide and gain limited benefit from this chemotherapy. Bortezomib depletes the MGMT enzyme, restoring the tumour´s susceptibility to Temozolomide, if the chemotherapy is administered in the precise schedule when the MGMT enzyme is depleted. Additionally, Bortezomib inhibits the growth of tumour cells by blocking autophagy flux. Temozolomide causes genotoxic stress in cancer cells that in turn respond by inducing protective processes such as autophagy. If both autophagy and MGMT DNA repair enzyme are blocked a priori, the efficacy of Temozolomide will be enhanced. Thus, pre-treating the tumour with Bortezomib prior to administration of Temozolomide leads to DNA repair enzyme depletion and blockade of autophagy-induced survival signals. The combined effect will sensitize the tumour to therapy, improve chemotherapy efficacy and prolong patient survival outcomes.

Hypothesis: Pretreatment with Bortezomib administered prior to Temozolomide will sensitize recurrent GBM with unmethylated MGMT promoter to standard TMZ in palliative setting.

Objective:

* Assessment of safety and tolerability of Bortezomib administered with Temozolomide.
* Determining the optimal dose of TMZ, when administered as combination therapy
* Estimate the progression free survival (PFS) and overall survival (OS) of patients with recurrent or progressed glioblastoma after pre-treatment with Bortezomib prior to combination with Temozolomide.

Key secondary objectives

* Tumour response to the therapy assessed by RANO and NANO criteria
* Determine physiological, molecular and biochemical changes in blood and tumour tissue that correlate with treatment responses.

Botezomib 1.3mg/m2 administered IV on days 1, 4, 7, during each 4-week chemotherapy cycle with per oral Temozolomide at three dose levels: 150 mg/m2, 175 mg/m2 and 200mg/m2 5 days/week every 4 weeks starting on day 3 until disease progression and/or unacceptable toxicity. Study group will be compared to historical controls on conventional management

Bortezomib and Temozolomide in Recurrent Grade-4 Glioma Unmethylated MGMT Promoter (BORTEM-17)

Bortezomib Sensitization of Recurrent Grade-4 Glioma With Unmethylated MGMT Promoter to Temozolomide Phase 1B/II Study

En intra- and inter-patient dose escalation period of TMZ administered after Bortezomib

Identification of novel tumor biomarkers by determining physiological, molecular and biochemical changes in blood and tumor tissue that correlate with treatment responses

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Bortezomib and Temozolomide in Recurrent Grade-4 Glioma Unmethylated MGMT Promoter (BORTEM-17)	NCT03643549	Glioblastoma	Bortezomib and ... Bortezomib and ...	18 Years -	Haukeland University Hospital
Bortezomib and Temozolomide in Recurrent Grade-4 Glioma Unmethylated MGMT Promoter (BORTEM-17)	NCT03643549	Glioblastoma	Bortezomib and ... Bortezomib and ...	18 Years -	Haukeland University Hospital

Spots Global Cancer Trial Database for bortezomib and temozolomide phase ib