Study of Tinostamustine for Adjuvant Treatment of Glioblastoma

NCT05432375 | Completed Early Phase 1 DMC

• 1 other identifier: EDO S101-1006
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 5

Brief Summary

The study is designed as an open label, multi-center, Phase 1 study of single agent tinostamustine, used as adjuvant treatment in patients with newly diagnosed GBM who are MGMT unmethylated and have completed concomitant treatment with temozolomide and radiation. Treatment with adjuvant tinostamustine will start within 5 weeks of completion of concomitant temozolomide and radiation. The study is designed to define the MTD by evaluating toxicities during dose escalation. Tinostamustine will be administered on Day 1 of a 21-day treatment cycle. The total number of treatment cycles is 12 for patients who continue to benefit from treatment without disease progression or intolerable toxicity. Patients will enter a "3+3" design with dose escalation/de-escalation depending on safety from the last treated cohort.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• Dose Limiting toxicity

  Toxicity will be evaluated according to the most current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) toxicity criteria

  cycle 1 of treatment. Cycle 1 is 21 days duration with infusion given on day 1

Secondary Outcomes (2)

• Anti-tumour activity

  Approx 1 year from start of treatment

• Pharmacokinetic assessment

  cycle 1 of treatment. Cycle is 21 days duration with infusion given on day 1

Study Arms (1)

Tinostamustine

EXPERIMENTAL

Infusion delivered over 60 minutes

Drug: Tinostamustine

Interventions

Tinostamustine DRUG

infusion given over 60 minutes

Tinostamustine

Eligibility Criteria

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

You may qualify if:

• Patients must have Grade 4 isocitrate dehydrogenase (IDH) wild type GBM with local pathology confirmed MGMT-promoter unmethylated status.

You may not qualify if:

• A baseline brain magnetic resonance imaging (MRI) obtained no more than 14 days prior to first dose of tinostamustine on a stable or decreasing dose of steroids for at least 5 days, is required prior to entrance of a patient onto the study.
• Patients must be registered on the study within 5 weeks of completion of concurrent chemoradiation.
• Patient must be willing and able to provide written informed consent for the study.
• Age ≥18 years on day of signing informed consent.
• Prescribed treatment with concomitant temozolomide must be consistent with the EORTC-22981-26981 study (NCT00006353). The dose must be 75 mg/m2 daily for the 6 to 6.5 weeks of radiation therapy. The patient must have completed at least 75% of temozolomide dosing during radiotherapy.
• Patients must have a performance status of ≥60 on the Karnofsky Performance Scale (KPS).
• If patient is on steroids, patient must be on a stable or decreasing dose of steroids for at least 5 days at the time of baseline brain MRI.
• Demonstrate adequate organ function as defined in Table 3. All screening laboratories should be performed within 14 days (+/- 2 days) of treatment initiation.
• Serum potassium and magnesium at least at the lowest limit of normal (LLN) range, before every tinostamustine administration. If it is below LLN, supplementation is permissible.
• Female patients of childbearing potential should have a negative serum pregnancy test within 48 hours of starting first dose of tinostamustine.
• Female study participants of childbearing potential and their partners, and male study participants who intend to be sexually active with a woman of childbearing potential, must be willing to use at least TWO highly effective forms of contraception. This should start from the time of study enrolment and continue throughout tinostamustine administration. Female study participants of childbearing potential must continue using contraception for at least 6 months after the last administration of the tinostamustine. Female study participants should be willing to have a pregnancy test performed at screening, on Day -1 of each tinostamustine administration and at tinostamustine discontinuation. Male study participants who are sexually active with a woman of childbearing potential should also use a condom during treatment and for at least 90 days after the last administration of tinostamustine. Vasectomised males are considered fertile; therefore, vasectomised partners and patients must be willing to use a secondary method of effective birth control. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the tinostamustine. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.
• Patient has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery. Prior treatment with Gliadel® wafers will be excluded. Concomitant use of the tumour treating fields will also be excluded.
• Use of chemotherapy or immunotherapy within 21 days (apart from TMZ), use of targeted therapy within 14 days or 5 times the half-life of the agent, whichever is longer, prior to the first dose of tinostamustine. After the respective durations mentioned above, patients may be enrolled if they have recovered from any related toxicities ≥ Grade 1 (except alopecia). This applies to any prior systemic anticancer therapy including investigational agents.
• Any serious medical condition that interferes with adherence to study procedures.
• Patient has had prior chemotherapy (excluding radiotherapy + temozolomide), targeted small molecule therapy, within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 at baseline) from AEs due to a previously administered agent.

Sponsors & Collaborators

• Mundipharma Research Limited: lead

Study Sites (5)

Hospital Universitario Vall d'Hebron, Barcelona, Spain

Barcelona, Spain

Location

Hospital Universitario Ramón y Cajal, Madrid, Spain

Madrid, Spain

Location

South Texas Accelerated Research Therapeutics (START)

Madrid, Spain

Location

Kantonsspital

Sankt Gallen, Switzerland

Location

University Hospital

Zurich, Switzerland

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

tinostamustine

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

Study Officials

• Tomas Janik, MD

  Mundipharma Research Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 27, 2022
• Study Start: July 1, 2022
• Primary Completion: November 10, 2024
• Study Completion: November 10, 2024
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); CH (2)