Bortem 17

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helse Bergen HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Oct 2024 → ongoing

Decision date (initial)

2024-10-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Norwegian Cancer Society · National Programme for Clinical Treatment Research in the Specialist Health Service

External identifiers

EU CT number

2024-515142-16-00

EudraCT number

2017-001690-16

ClinicalTrials.gov

NCT03643549

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Phase IB: Assessment of safety and tolerability of Bortezomib administered with Temozolomide. Determination of the optimal dose of TMZ and BTZ given as combination therapy. Sample size 10 patients.
Phase II: Assessment of efficacy of Bortezomib administered with Temozolomide. Sample size 53 patients.Estimation of the median progression free survival (PFS) and overall survival (OS) of patients with recurrent or progressed grade-4 glioma after pre-treatment with Bortezomib prior to combination with Temozolomide as well as progression free rate at 6 months

Secondary objectives 3

1. Identifying novel biomarkers by determining physiological, molecular and biochemical changes in blood and tumour tissue that correlate with treatment responses
2. Changes in natural killer cell phenotype and function
3. Changes in autophagy flux

Conditions and MedDRA coding

Grade IV recurrent glioma which includes both glioblastoma, classified as IDH wt and grade IV IDH mutated astrocytoma.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 28

1. Histologically confirmed recurrent or progressed WHO grade IV intracranial IDH wildtype glioblastoma (GBM) or grade IV IDH mutated astrocytoma, MRI evidence of recurrence within 14 days prior to enrolment
2. Unmethylated MGMT promoter characterised from tissue obtained at operation
3. Must submit an unstained paraffin block and/or cryopreserved tumour tissue from surgical procedure
4. Must be >- 18 years old, with a life expectancy > 8 weeks
5. Radiologically (MRI) confirmed tumour relapse/progression ≥ 12 weeks since completed radiotherapy
6. Measurable recurrent tumour
7. Tumour not available for radiosurgery
8. Patients previously treated with radiosurgery er eligible for the study
9. 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
10. Written informed consent for study participation and tumour, blood sample collection obtained before performance of any study related procedure
11. Karnofsky performance status ≥ 70%
12. WBC ≥ 3,000/mm^3
13. ANC ≥ 1,500/mm^3
14. Platelet count ≥ 100,000/mm^3
15. Prothrombin time/international normalized ratio (PT INR) < 1.4.
16. Haemoglobin ≥ 10 g/dL (transfusion allowed)
17. Adequate hepatic function: serum bilirubin, AST, ALT and alkaline phosphatase ≤ 2.5 upper limit of normal (ULN)
18. Serum potassium within normal limit
19. Serum sodium > 130 mmol/L
20. Estimated GFR ≥ 60
21. Stable or reduced doses of corticosteroids for at least 1 week prior to enrolment, but analgesics and other drugs to treat symptoms or prevent complications allowed
22. Patients receiving EIAED must be transitioned to non-EIAED at least 2 weeks before study inclusion
23. Unfractionated and/or low molecular weight heparin is allowed
24. Other investigational drugs must be discontinued at least 12 weeks prior to study entry unless treatment failure under other experimental therapy is confirmed. If progression during other experimental therapy is confirmed the time interval between previous treatment and BORTEM-17 may be reduced to 4 weeks
25. Eligibility for standard therapy with Temozolomid as 5-days treatment q4w.
26. Negative pregnancy test no longer than 14 days prior to enrollment
27. Women of childbearing potential (WOCBP) defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile must use adequate contraception. Permanent sterilization methods include hysterectomy, bilateral salpingectomy or bilateral oophorectomy
28. Men in sexual relationship with WOCBP must agree to use a condom during treatment and until 3 months after the last dose of bortezomib and 6 months after the last dose of TMZ

Exclusion criteria 17

1. Hypersensitivity to Bortezomib, boron, or mannitol
2. Any contraindications for use of Temozolomid
3. Peripheral neuropathy ≥ grade 2
4. Previous treatment with bevacizumab or lomustine either as monotherapy or in combination with procarbazine and vincristine for ralapsed glioblastoma (PCV as primary treatment of low grade oligodendroglioma, before development of glioblastoma is allowed)
5. Myocardial infarction within the past 6 months
6. NYHA class III or IV heart failure
7. Uncontrolled angina
8. Severe uncontrolled ventricular arrhythmias
9. Known heart failure
10. Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
11. Serious medical or psychiatric illness that would interfere with study participation including, but not limited to, any of the following: - Psychiatric illness and/or social situations that would limit compliance with study requirements - Ongoing, uncontrolled infection requiring IV antibiotics - Disorders associated with a significant immunocompromised state (e.g., HIV, systemic lupus erythematosus) - History of stroke within the past 6 months - Other malignancy within the past 3 years except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy (i.e., cervical cancer), or low-risk prostate cancer after curative therapy
12. Significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
13. Disease that will obscure toxicity or dangerously alter drug metabolism
14. Viral hepatitis (HBV surface antigen positive) or active hepatitis C infection
15. Concurrent investigational drugs (chemotherapy) must be stopped at least 12 weeks prior to therapy or treatment failure under other experimental therapy must be confirmed before study entry. If progression during previous experimental therapy is confirmed the time interval before BORTEM-17 study entry may be reduced to 6 weeks.
16. Concurrent use of any inducers of CYP450 3A4 including, but not limited to enzyme-inducing anti-epileptic drugs [EIAED] e.g. phenytoin, fosphenytoin, carbamazepine, phenobarbital, or primidone.
17. Another ongoing experimental therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase IB of the trial: Assessment of safety and tolerability of Bortezomib administered with Temozolomide.
2. Phase II: Assessment of efficacy of Temozolomide administered together with Bortezomib in recurrent glioblastoma. Overall survival (OS) at 1 year. Median OS from the 1st relapse. Progression free survival at 6 months. Median PFS from the 1st relapse. Time to progression.

Secondary endpoints 3

1. Tumour response as assessed by contrast enhanced MRI using RANO criteria and neurological exam, [Time Frame: MRI at start of treatment and every 12th week, neurologic exam every 4 weeks]. If disease progression is suspected according to NANO criteria (clinical assessment) further confirmation with MRI (RANO) is required.
2. Neurologic assessment according to NANO criteria [Time Frame: neurologic exam every 4 weeks]
3. Identification of novel tumor biomarkers by determining physiological, molecular and biochemical changes in blood and tumor tissue that correlate with treatment responses

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helse Bergen HF

Sponsor organisation

Helse Bergen HF

Address

Haukelandsveien 22

City

Bergen

Postcode

5021

Country

Norway

Scientific contact point

Organisation

Helse Bergen HF

Contact name

Dorota Goplen

Public contact point

Organisation

Helse Bergen HF

Contact name

Dorota Goplen

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications