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

NCT03643549 | Recruiting Phase 1 DMC

• 1 other identifier: 2017/2084
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Glioblastoma

Keywords

Temozolomide; Bortezomib; Recurrent disease

Outcome Measures

Primary Outcomes (4)

• Bortezomib-Temozolomide Maximum tolerated dose

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

  6 months

• Overall survival

  Overall survival at 1 year

  1 year

• Progression free survival

  Progression free survival at 6 months

  6 months

• Time to progression

  Median time

  4 years

Secondary Outcomes (4)

• Biomarkers of treatment response

  4 years

• Tumour responses

  4 years

• Clinical response

  4 years

• Toxicity assessment

  4 years

Study Arms (1)

Bortezomib and Temozolomide

EXPERIMENTAL

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.

Drug: Bortezomib and Temozolomide Phase IB; Drug: Bortezomib and Temozolomide Phase II

Interventions

Bortezomib and Temozolomide Phase IB DRUG

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

Bortezomib and Temozolomide Phase II DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Life expectancy \> 8 weeks
• Histologically confirmed intracranial glioblastoma (GBM), with MGMT unmethylated promoter
• Must submit an unstained paraffin block and/ or cryopreserved tumour tissue from surgical procedure
• Radiologically (MRI) confirmed tumour relapse/progression ≥ 12 weeks since completed radiotherapy
• Measurable recurrent tumor
• Tumor not available for radio-surgery
• If previously treated with gammaknife, at least one evaluable lesion outside the irradiated area is required, unless the time after the radiosurgery is 12 weeks or more
• Written informed consent for study participation and tumour, blood sample collection obtained before performance of any study related procedure.
• Karnofsky performance status ≥ 70
• WBC ≥ 3,000/mm\^3
• ANC ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• Bilirubin \< 2.5 times upper limit of normal (ULN)
• serum aspartate aminotransferase (AST) \< 2.5 times ULN

You may not qualify if:

• Hypersensitivity to Bortezomib, boron, or mannitol
• Any contraindications for use of temozolomide
• Peripheral neuropathy ≥ grade 2
• Previous treatment with bevacizumab or lomustine alone or as a combination therapy for ralapsed glioblastoma (PCV as primary treatment of low grade glioma, before development of glioblastoma, is allowed)
• Myocardial infarction within the past 6 months
• NYHA class III or IV heart failure
• Uncontrolled angina
• Severe uncontrolled ventricular arrhythmias
• Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Known heart failure
• Serious medical or psychiatric illness that would interfere with the study participation including, but not limited to, any of the following:
• Ongoing or active infection requiring IV antibiotics
• Psychiatric illness and/or social situations that would limit compliance with study requirements
• Disorders associated with a significant immunocompromised state (e.g., HIV, systemic lupus erythematosus)
• History of stroke within the past 6 months

Sponsors & Collaborators

• Haukeland University Hospital: lead
• Oslo University Hospital: collaborator
• St. Olavs Hospital: collaborator
• University Hospital of North Norway: collaborator
• University of Bergen: collaborator
• University of Bonn: collaborator
• University of Oslo: collaborator

Study Sites (2)

Haukeland University Hospital

Bergen, 5021, Norway

RECRUITING

Oslo University Hospital

Oslo, 0424, Norway

RECRUITING

Related Publications (1)

• Rahman MA, Brekke J, Arnesen V, Hannisdal MH, Navarro AG, Waha A, Herfindal L, Rygh CB, Bratland E, Brandal P, Haasz J, Oltedal L, Miletic H, Lundervold A, Lie SA, Goplen D, Chekenya M. Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study. Immun Inflamm Dis. 2020 Sep;8(3):342-359. doi: 10.1002/iid3.315. Epub 2020 Jun 24.

  PMID: 32578964 DERIVED

MeSH Terms

Conditions

Glioblastoma; Recurrence

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dorota Goplen, MD, PhD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dorota Goplen, MD, PhD

CONTACT

+47 55974019; dgop@helse-bergen.no

Martha E Chekenya, PhD, Dr. Philos

CONTACT

+47 55586380; martha.enger@uib.no

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 22, 2018
• Study Start: August 30, 2018
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: February 29, 2024

Record last verified: 2024-02

Locations

NO (2)