Trial Title:
A Study of Debio 0123 in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Debio 0123 in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma
NCT ID:
NCT05765812
Condition:
Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype
Astrocytoma, Grade III
Conditions: Official terms:
Glioblastoma
Astrocytoma
Temozolomide
Conditions: Keywords:
WEE1 inhibitor
Glioblastoma, IDH-wildtype, Grade 4, World Health Organization (WHO) 2021
Astrocytoma, IDH-mutant, Grade 3, WHO 2021
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Parallel assignment applies to the arm groups within Phase 1 of the study. Sequential
assignment will apply to Phases 1 and 2 of the study.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Debio 0123
Description:
Administered as capsules.
Arm group label:
Phase 1 (Dose Escalation): Arm A - Debio 0123 + Temozolomide
Arm group label:
Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy
Arm group label:
Phase 1 (Dose Escalation): Arm C - Debio 0123 + Temozolomide + Radiotherapy
Arm group label:
Phase 1 (Dose Expansion): Debio 0123 + Temozolomide
Arm group label:
Phase 2: Debio 0123 RD + Temozolomide
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Administered as capsules.
Arm group label:
Phase 1 (Dose Escalation): Arm A - Debio 0123 + Temozolomide
Arm group label:
Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy
Arm group label:
Phase 1 (Dose Escalation): Arm C - Debio 0123 + Temozolomide + Radiotherapy
Arm group label:
Phase 1 (Dose Expansion): Debio 0123 + Temozolomide
Arm group label:
Phase 2: Debio 0123 RD + Temozolomide
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
Administered in accordance with the local clinical practice and applicable Radiation
Therapy Oncology Group (RTOG) or the European Organization for Research and Treatment of
Cancer (EORTC) guidelines.
Arm group label:
Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy
Arm group label:
Phase 1 (Dose Escalation): Arm C - Debio 0123 + Temozolomide + Radiotherapy
Summary:
The primary purpose of the Phase 1 (Dose Escalation) of this study is to identify the
dose-limiting toxicities (DLTs) of Debio 0123 combined with temozolomide (TMZ) (Arm A)
and with TMZ and radiotherapy (RT) (Arms B and C) and to characterize the safety and
tolerability of these combinations in adult participants with glioblastoma (GBM). Arm B
which was previously added to the protocol, has been permanently halted per the safety
monitoring committees' decision on the safety findings of this arm.
The primary purpose of Phase 1 (Dose expansion) of the study is to assess the doses
studied under Phase 1 (Dose Escalation) Arm A and identify the recommended dose (RD) for
further development.
The Phase 2 will start once the RD Phase 1 has been defined. The primary objective of
Phase 2 is to assess the efficacy of Debio 0123 at the RD for further development in
combination with TMZ, compared to the standard of care (SOC) in adult participants with
GBM.
Criteria for eligibility:
Criteria:
Screening Inclusion Criteria for Phase 1 and Phase 2:
- Signed written informed consent approved before undertaking any study-specific
procedures.
- Age ≥18 years of age.
- Willing to provide archived or fresh tumor sample, if available. Receipt of tumor
sample is not required for the start of study treatment.
- Adequate bone marrow, hepatic, and renal function.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures.
- Willing to practice highly effective methods of contraception.
- Life expectancy of at least 3 months in the best judgment of the Investigator.
- Measurable or non-measurable disease as per RANO criteria by gadolinium (Gd)-based
contrast-enhanced brain magnetic resonance imaging (MRI).
- Participants receiving corticosteroids must be on a stable or decreasing dose of ≤4
mg daily dexamethasone (or ≤25 mg prednisone) for the 7 days prior to the start of
study treatment.
- Participants with seizures must be adequately controlled on a stable regimen of
anti-epileptic drugs.
Additional specific inclusion criteria for Phase 1 and Phase 2:
• A maximum of 1 [for Phase 1 (Dose Expansion) and phase 2] or 2 (Phase 1 Arm A) prior
treatment lines of which first-line must be treatment with TMZ-based chemoradiotherapy
(TMZ concomitantly with RT).
Note: Only 1 prior line of systemic therapy is allowed; combination therapy with TMZ and
RT with or without subsequent TMZ maintenance treatment is considered as 1 systemic line.
Prior surgery, radiation, or localized delivery of therapeutic agents (i.e.,
carmustine-containing wafers [GLIADEL®]) for first recurrence is allowed.
- Documented disease recurrence or progression by diagnostic biopsy or Gd-based
contrast-enhanced brain MRI as per RANO criteria.
- KPS ≥60.
Additional specific inclusion criteria for Phase 1 Arm A:
- Participants must have one of the following histopathologically proven diagnoses
(WHO 2021):
- GBM Isocitrate dehydrogenase (IDH)-wildtype Grade 4 which may include secondary GBMs
(i.e., those that progress from low-grade gliomas).
- Astrocytoma, IDH-mutant, Grade 3
Additional specific inclusion criteria for Phase 1 Arm B and C:
- Participants must have a new, histopathologically proven diagnosis of GBM,
IDH-wildtype, Grade 4 (based on WHO 2021), which may include secondary GBMs (i.e.,
those that progress from low-grade gliomas) if the prior treatment included surgery
only.
- KPS ≥70.
Additional specific inclusion criteria for Phase 1 dose expansion and Phase 2:
• Participants must have a histopathologically proven diagnosis of GBM, IDH-wildtype
Grade 4 WHO 2021
Additional specific exclusion criteria for Phase 1 Arm A • Prior treatment with more than
2 lines of therapy for GBM, IDH-wildtype, Grade 4, or for astrocytoma, IDH-mutant, Grade
3
Additional specific exclusion criteria for Phase 1 and Phase 2
- Known contraindication to undergoing for Gd-based, contrast-enhanced MRI.
- Chemotherapy, monoclonal antibodies/biologics, investigational treatment, or RT with
curative intent within 28 days prior to starting study treatment.
- Exposure to high levels of ultraviolet (UV) light, for example occupational exposure
to sunlight or sunbathing.
- Hypersensitivity to Debio 0123, TMZ, dacarbazine, or any of the excipients found in
the formulation for Debio 0123 or TMZ.
- Prior exposure to any WEE1 inhibitor.
- History of other malignancies requiring active treatment in the last 2 years prior
to the first dose of study treatment except for superficial bladder cancers,
adequately treated low-risk prostate cancer under active surveillance, ductal
carcinoma in situ or other carcinomas in situ, and non-melanoma skin cancers (basal
cell/squamous cell skin cancer) that have been treated with curative intent.
- Left ventricular ejection fraction (LVEF) below 55%.
Additional specific exclusion criteria for Phase 1 Arm B and C:
- Prior radiation, chemotherapy, biological therapy, interstitial brachytherapy,
implanted chemotherapy, therapeutics delivered by local injection or
convection-enhanced delivery for GBM.
- Prior therapy that would result in an overlap of the radiation fields.
Additional specific exclusion criteria for Phase 1 dose expansion and Phase 2
• Prior treatment with more than 1 line of systemic therapy for GBM, IDH-wildtype, Grade
4 (based on WHO 2021). Combination therapy with TMZ and RT with or without subsequent TMZ
maintenance treatment is considered as 1 systemic line.
[Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.]
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
New York University Langone Medical Center
Address:
City:
New York
Zip:
10016
Country:
United States
Status:
Recruiting
Facility:
Name:
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Recruiting
Facility:
Name:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
South Texas Accelerated Research Therapeutics (START)
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Facility:
Name:
Fred Hutchinson Cancer Research Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Facility:
Name:
Hospital Universitario Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Clinica Universidad de Navarra (CUN)
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Status:
Recruiting
Facility:
Name:
South Texas Accelerated Research Therapeutics (START)
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Facility:
Name:
Clinica Universidad de Navarra (CUN)
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Clinico Universitario de Valencia
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Universitaetsspital Zuerich
Address:
City:
Zuerich
Zip:
CH-8091
Country:
Switzerland
Status:
Recruiting
Start date:
May 15, 2023
Completion date:
September 2028
Lead sponsor:
Agency:
Debiopharm International SA
Agency class:
Industry
Source:
Debiopharm International SA
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05765812
