AzTrials
AzTrials

GlioblastomaPhase 1/2NCT02770378

A Proof-of-concept Clinical Trial Assessing the Safety of the Coordinated Undermining of Survival Paths by 9 Repurposed Drugs Combined With Metronomic Temozolomide (CUSP9v3 Treatment Protocol) for Recurrent Glioblastoma

A Phase 1/2 study testing Temozolomide, Aprepitant and Minocycline in people with Glioblastoma, run by University of Ulm at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

A proof-of-concept clinical trial assessing the safety of the coordinated undermining of survival paths by 9 repurposed drugs combined with metronomic temozolomide (CUSP9v3 treatment protocol) for recurrent glioblastoma Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma
What is being tested?
Temozolomide, Aprepitant and Minocycline
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteGermany
Study dates
Nov 2016to Dec 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with a diagnosis of glioblastoma World Health Organization (WHO) grade IV (histologically confirmed by a pathologist). Patients with prior low-grade glioma are eligible if histological transformation to WHO grade IV glioblastoma was confirmed.
  • Progression (according to RANO criteria) after prior radiation and temozolomide treatment
  • No more than 3 prior episodes of tumor progression
  • ≥ 4 weeks between surgical resection or chemotherapy
  • ≥ 12 weeks since last radiotherapy
  • Patients > 18 years of age.
Show all 16Show fewer
  • Karnofsky performance status (KPS) of ≥ 70%
  • Stable steroid dose for ≥ 1 week
  • Hemoglobin ≥ 10 g/l
  • Absolute neutrophil count (ANC) > 10³ cells/µl
  • Platelet count > 100/µl
  • Maximum 5 years since last Pneumovax (or equivalent) and varicella vaccination
  • Serum creatinine, aspartat-aminotransferase (AST) and bilirubin ≤ 1.5 times the upper limit of normal (ULN)
  • Female patients of childbearing potential with a negative pregnancy test within 7 days of initiation of study treatment. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  • Male and female patients of reproductive potential who agree to employ an effective method of birth control throughout the study and for up to 6 months following discontinuation of study drug. Patients must be counseled on the possibility of cryopreservation of oocytes or sperm.
  • Signed informed consent prior to initiation of any study procedure (must understand, voluntarily sign the informed consent form and be able to adhere to the study visit schedule and other protocol requirements).

Who cannot join

  • Female patients who are pregnant or breast-feeding
  • Any uncontrolled/unstable medical condition except glioblastoma, including but not limited to uncontrolled/unstable hypertension, uncontrolled/unstable diabetes, uncontrolled endocrinopathies of any kind, uncontrolled/unstable psychiatric conditions
  • Renal failure (eGFR < 60 ml/min)
  • Active infection, including pneumonia as shown on X-ray
  • Therapeutic anticoagulation use
  • Prior stereotactic radiosurgery
Show all 18Show fewer
  • Radiation implants
  • Radiolabeled monoclonal antibody therapy unless there was unequivocal disease progression (e.g. a new lesion or biopsy-confirmed recurrence)
  • QT interval (QTc) < 470 msec (based on the mean value of triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome, or known history of QTc prolongation or Torsade de Pointes
  • Uncontrolled electrolyte disorders that can aggravate the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia)
  • History of severe hypersensitivity reaction (≥ grade 3) to any component of the investigational drugs or excipients
  • Unable to undergo contrast-enhanced MRI
  • Patients who have been treated with any investigational agent(s) within 28 days of the first day of administration of study drugs
  • Current active second malignancy other than non-melanoma skin cancers and post-treatment of localized prostate cancer. Patients are not considered to have a currently active malignancy if they are in complete remission for > 3 years prior to study
  • Known HIV infection, active Hepatitis B or C infection
  • Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity (except alopecia) and delayed recovery following last temozolomide cycle
  • Additional anti-cancer treatment for glioblastoma other than study drug and supportive measures (i.e. dexamethasone)
  • Patients refusing consent for registration, storage, and processing of individual disease characteristics, information on the course of the disease, and information obtained from the family physician and/or other physicians involved in the treatment of the patient about study participation.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • University of Ulm School of Medicine

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

About this study

A proof-of-concept clinical trial assessing the safety of the coordinated undermining of survival paths by 9 repurposed drugs combined with metronomic temozolomide (CUSP9v3 treatment protocol) for recurrent glioblastoma

Read the detailed description

A proof-of-concept clinical trial assessing the safety of the coordinated undermining of survival paths by 9 repurposed drugs (aprepitant, auranofin, captopril, celecoxib, disulfiram, itraconazole, minocycline, ritonavir and sertraline) combined with metronomic temozolomide (CUSP9v3 treatment protocol) for recurrent glioblastoma. This is a phase I study for subjects of 18 years and older with glioblastoma that has relapsed after radiation and chemotherapy, as confirmed by histology and MRI.

A total of 10 patients will be treated with the CUSP9v3 treatment protocol. This is a monocentric trial: all patients will be treated at Ulm University Hospital.

Conditions
Glioblastoma
Being tested
Temozolomide, Aprepitant, Minocycline, Disulfiram, Celecoxib
Keywords
Temozolomide, Recurrent Glioblastoma
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemozolomideDrug

    Patients will receive temozolomide at a dose of 20 mg/m² BSA twice daily with start day 1 during induction and treatment cycles

  • AprepitantDrug

    Patients will receive aprepitant at a dose of 80 mg p.o. once daily with start day 1 during induction and treatment cycles

  • MinocyclineDrug

    Induction cycle day 3-4: minocycline 50 mg p.o. twice daily from day 19-20; minocycline 100 mg p.o. twice daily during treatment cycle 1-12 (28 days); minocycline 100 mg p.o. twice daily

  • DisulfiramDrug

    Induction cycle day 5-6: disulfiram 250 mg p.o. once daily from day 21-22; disulfiram 250 mg p.o. twice daily during treatment cycle 1-12 (28 days); disulfiram 250 mg p.o. twice daily

  • CelecoxibDrug

    Induction cycle day 1-35: day 7-8: celecoxib 200 mg p.o. twice daily from day 23-24; celecoxib 400 mg p.o. twice daily during treatment cycle 1-12 (28 days); celecoxib 400 mg p.o.twice daily

  • SertralineDrug

    Induction cycle day 1-35: day 9-10: sertraline 50 mg p.o. twice daily, day 31-32: sertraline 100 mg p.o. twice daily; treatment cycle 1-12: sertraline 100 mg p.o. twice daily

  • CaptoprilDrug

    Induction cycle day 1-35: day 11-12: captopril 25 mg p.o. twice daily, day 25-26: captopril 50 mg p.o. twice daily; treatment cycle 1-12 (28 days): captopril 50 mg p.o. twice daily

  • ItraconazoleDrug

    Induction cycle day 1-35: day 13-14: itraconazole 200 mg p.o. once daily day 27-28; itraconazole 200 mg p.o. twice daily; treatment cycle 1-12 (28 days): itraconazole 200 mg p.o.twice daily

  • RitonavirDrug

    Induction cycle day 1-35: day 15-16: ritonavir 200 mg p.o. once daily, day 29-30: ritonavir 200 mg p.o. twice daily, day 35: ritonavir 400 mg p.o. twice daily; treatment cycle 1-12 (28 days): ritonavir 400 mg p.o. twice daily

  • AuranofinDrug

    Induction cycle day 1-35: day 17-18: auranofin 3 mg p.o. once daily, day 33-34 auranofin 3 mg p.o. twice daily; treatment cycle 1-12 auranofin 3 mg p.o. twice daily

Study groups in NCT02770378
Study groupRoleWhat they receive
Temozolomide combined with 9 repurposed drugsExperimentalAfter enrollment, the subject goes into the induction cycle, which lasts 35 days. The induction cycle consists of a drug-by-drug addition and up-dosing process. Hereafter, the subject will enter the treatment cycles (up to 12). During the induction cycle and the first 2 treatment cycles, regimen adjustments (dropping of certain drugs, dose modification of certain drugs) may be executed to accommodate to the patients' individual toxicity reactions that may occur during this period.
Receives: Drug: Temozolomide; Drug: Aprepitant; Drug: Minocycline; Drug: Disulfiram; Drug: Celecoxib; Drug: Sertraline; Drug: Captopril; Drug: Itraconazole; Drug: Ritonavir; Drug: Auranofin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Endpoint for phase Ib is the number of patients experiencing dose-limiting toxicity defined as:

    • either any unmanageable grade 3-4 toxicity at the end of the second treatment cycle
    • or inability to receive at least 7 of the 10 drugs, all of them being given at ≥50% of the target doses at the end of the second treatment cycle
    • Modifications in terms of doses and/or number of drugs are accepted at any time during treatment.

    Measured: Week 12

  2. Endpoint for phase IIa of the trial is objective stable disease or a better tumor response (i.e., partial response, complete response)

    as assessed by non-contrast and contrast-enhanced standard cranial MRI interpreted using RANO criteria after 6 treatment cycles in comparison to the baseline MRI.

    Measured: Week 12

Secondary outcomes (3)

  1. Overall survival according to Kaplan-Meier estimates

    Measured: through study completion, an average of 1 year

  2. Progression-free survival according to Kaplan-Meier estimates

    Measured: through study completion, an average of 1 year

  3. Best tumor response according to the Revised Assessment in Neuro-Oncology (RANO) criteria

    Measured: through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionOct 2018
  4. Study completionDec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02770378
Sponsor's protocol ID
CUSP9v3
Status last verified
Oct 2021
First submitted
14 Mar 2016
Last updated
5 Oct 2021
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Cao Q, Hajosch A, Kast RE, Loehmann C, Hlavac M, Fischer-Posovszky P, Strobel H, Westhoff MA, Siegelin MD, Wirtz CR, Halatsch ME, Karpel-Massler G. Tumor Treating Fields (TTFields) combined with the drug repurposing approach CUSP9v3 induce metabolic reprogramming and synergistic anti-glioblastoma activity in vitro. Br J Cancer. 2024 May;130(8):1365-1376. doi: 10.1038/s41416-024-02608-8. Epub 2024 Feb 23.

    PubMed 38396172

  • Halatsch ME, Dwucet A, Schmidt CJ, Muhlnickel J, Heiland T, Zeiler K, Siegelin MD, Kast RE, Karpel-Massler G. In Vitro and Clinical Compassionate Use Experiences with the Drug-Repurposing Approach CUSP9v3 in Glioblastoma. Pharmaceuticals (Basel). 2021 Nov 29;14(12):1241. doi: 10.3390/ph14121241.

    PubMed 34959641

  • Romo-Perez A, Dominguez-Gomez G, Chavez-Blanco A, Taja-Chayeb L, Gonzalez-Fierro A, Garcia-Martinez E, Correa-Basurto J, Duenas-Gonzalez A. BAPST. A Combo of Common Use Drugs as Metabolic Therapy for Cancer: A Theoretical Proposal. Curr Mol Pharmacol. 2022;15(6):815-831. doi: 10.2174/1874467214666211006123728.

    PubMed 34620071

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Temozolomide, Aprepitant and Minocycline in people with Glioblastoma, run by University of Ulm at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Endpoint for phase Ib is the number of patients experiencing dose-limiting toxicity defined as: (time frame: Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02770378, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2021; AzTrials last refreshed its copy on 8 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in