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NCT05765812 | RECRUITING | Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype

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
Sponsor:

Debiopharm International SA

Brief 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.

Condition or disease

Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype

Astrocytoma, Grade III

Intervention/treatment

Debio 0123

Temozolomide

Radiotherapy

Phase

PHASE1

PHASE2

Study Type : INTERVENTIONAL
Estimated Enrollment : 116 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : A Phase 1/2 Open-label 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
Actual Study Start Date : 2023-05-15
Estimated Primary Completion Date : 2028-09
Estimated Study Completion Date : 2028-09

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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.
          • * Any anticancer treatment, monoclonal antibodies/biologics, investigational treatment, or RT with curative intent within 28 days prior to starting study treatment.
          • * 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.
            • \[Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.\]
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

Location Details

NCT05765812

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

RECRUITING

United States, New York

New York University Langone Medical Center

New York, New York, United States, 10016

RECRUITING

United States, New York

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10021

NOT YET RECRUITING

United States, Texas

Baylor Scott & White Research Institute

Dallas, Texas, United States, 75246

RECRUITING

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

RECRUITING

United States, Texas

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States, 78229

NOT YET RECRUITING

United States, Utah

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

RECRUITING

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

RECRUITING

Spain,

Vall d'Hebron University Hospital

Barcelona, Spain, 08035

NOT YET RECRUITING

Spain,

Donostia University Hospital

San Sebastián, Spain, 20014

RECRUITING

Spain,

Clinic University of Navarra (CUN)

Madrid, Spain, 28027

RECRUITING

Spain,

South Texas Accelerated Research Therapeutics (START)

Madrid, Spain, 28040

RECRUITING

Spain,

October 12 University Hospital

Madrid, Spain, 28041

RECRUITING

Spain,

Clinic University of Navarra (CUN)

Pamplona, Spain, 31008

NOT YET RECRUITING

Spain,

Donostia University Hospital

San Sebastián, Spain, 20014

NOT YET RECRUITING

Spain,

University Clinic Hospital of Valencia

Valencia, Spain, 46010

RECRUITING

Switzerland,

Universitaetsspital Zuerich

Zuerich, Switzerland, CH-8091