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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

Primary Purpose

Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype, Astrocytoma, Grade III

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Debio 0123
Temozolomide
Radiotherapy
Sponsored by
Debiopharm International SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype focused on measuring WEE1 inhibitor, Glioblastoma, IDH-wildtype, Grade 4, World Health Organization (WHO) 2021, Astrocytoma, IDH-mutant, Grade 3, WHO 2021

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Screening Inclusion Criteria for Phase 1 Arm A 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 Arm A and Phase 2: A maximum of 1 (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). 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: GBM Isocitrate dehydrogenase (IDH)-wildtype Grade 4 (based on WHO 2021), which may include secondary GBMs (i.e., those that progress from low-grade gliomas). Astrocytoma, IDH-mutant, Grade 3 (based on WHO 2021). Additional specific inclusion criteria for Phase 1 Arm B: 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). KPS ≥70. Additional specific inclusion criteria for Phase 2: Participants must have a histopathologically proven diagnosis of GBM, IDH-wildtype Grade 4 (based on WHO 2021). 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 based on WHO 2021. Exclusion Criteria for Phases 1 and 2: Known contraindication 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%. Specific exclusion criteria for Phase 1 Arm A and Phase 2: Prior treatment with bevacizumab or with other vascular endothelial growth factor (VEGF) inhibitors or VEGF-receptor signaling inhibitors. Prior TMZ-related hematological event leading to discontinuation of TMZ during the concurrent chemoradiotherapy. Specific exclusion criteria for Phase 1 Arm B: 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. Exclusion criteria for 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 line. [Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.]

Sites / Locations

  • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer CenterRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • South Texas Accelerated Research Therapeutics (START)Recruiting
  • Fred Hutchinson Cancer Research CenterRecruiting
  • Hospital Universitario Vall d'HebronRecruiting
  • Clinica Universidad de Navarra (CUN)Recruiting
  • South Texas Accelerated Research Therapeutics (START)Recruiting
  • Hospital Universitario 12 de OctubreRecruiting
  • Clinica Universidad de Navarra (CUN)Recruiting
  • Universitaetsspital ZuerichRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase 1: Arm A - Debio 0123 + Temozolomide

Phase 1: Arm B - Debio 0123 + Temozolomide + Radiotherapy

Phase 2: Debio 0123 RP2D + Temozolomide

Arm Description

Participants will receive Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years.

Participants will receive Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.

Participants will receive Debio 0123 RP2D along with TMZ in each 28-day cycle for up to 2 years.

Outcomes

Primary Outcome Measures

Phase 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Phase 1: Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)
Phase 1: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and Electrocardiogram (ECG) Parameters
Phase 1: Change From Baseline in Karnofsky Performance Status (KPS) Score
KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.
Phase 2: Overall Survival (OS)

Secondary Outcome Measures

Phases 1 and 2: Plasma Concentration of Debio 0123 and its Metabolite
The pharmacokinetics (PK) of Debio-0123 and its metabolite will be evaluated in plasma.
Phases 1 and 2: Percentage of Participants With Best Overall Response (BOR) Assessed As Per Response Assessment in Neuro-oncology (RANO) Criteria
Phases 1 and 2: Percentage of Participants With Objective Response (OR) Assessed As Per RANO Criteria
Phases 1 and 2: Percentage of Participants With Disease Control (DC) Assessed As Per RANO Criteria
Phases 1 and 2: Duration of Response (DOR) Assessed As Per RANO Criteria
Phases 1 and 2: Progression Free Survival (PFS) Assessed As Per RANO Criteria
Phase 1: Plasma Concentration of Temozolomide
The PK of temozolomide will be evaluated in plasma.
Phase 2: Number of Participants With At Least One TEAE
Phase 2: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and ECG Parameters
Phase 2: Change From Baseline in KPS Score
KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.

Full Information

First Posted
February 15, 2023
Last Updated
September 27, 2023
Sponsor
Debiopharm International SA
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1. Study Identification

Unique Protocol Identification Number
NCT05765812
Brief 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
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
March 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Debiopharm International SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary purpose of Phase 1 (dose escalation) of this study is to identify the recommended Phase 2 dose (RP2D) of Debio 0123 in combination with temozolomide (TMZ) (Arm A) and in combination with TMZ and radiotherapy (RT) (Arm B) and to characterize the safety and tolerability of these combinations in adult participants with glioblastoma (GBM). The primary purpose of Phase 2 of this study is to assess the efficacy of Debio 0123 at the RP2D in combination with TMZ, compared to standard of care (SOC) in adult participants with GBM.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype, Astrocytoma, Grade III
Keywords
WEE1 inhibitor, Glioblastoma, IDH-wildtype, Grade 4, World Health Organization (WHO) 2021, Astrocytoma, IDH-mutant, Grade 3, WHO 2021

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
89 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1: Arm A - Debio 0123 + Temozolomide
Arm Type
Experimental
Arm Description
Participants will receive Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years.
Arm Title
Phase 1: Arm B - Debio 0123 + Temozolomide + Radiotherapy
Arm Type
Experimental
Arm Description
Participants will receive Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.
Arm Title
Phase 2: Debio 0123 RP2D + Temozolomide
Arm Type
Experimental
Arm Description
Participants will receive Debio 0123 RP2D along with TMZ in each 28-day cycle for up to 2 years.
Intervention Type
Drug
Intervention Name(s)
Debio 0123
Intervention Description
Administered as capsules.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
Administered as capsules.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention 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.
Primary Outcome Measure Information:
Title
Phase 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Time Frame
Phase 1: Arm A: Cycle 1 (Cycle=28 days); Arm B: Up to approximately 1.9 months
Title
Phase 1: Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)
Time Frame
Up to 30 days after the end of treatment (Arm A: Up to approximately 26 months and Arm B: Up to approximately 3.5 months)
Title
Phase 1: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and Electrocardiogram (ECG) Parameters
Time Frame
Up to 30 days after the end of treatment (Arm A: Up to approximately 26 months and Arm B: Up to approximately 3.5 months)
Title
Phase 1: Change From Baseline in Karnofsky Performance Status (KPS) Score
Description
KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.
Time Frame
Until disease progression or end of study (approximately 54 months)
Title
Phase 2: Overall Survival (OS)
Time Frame
From the start of study treatment until death from any cause or end of study (up to approximately 54 months)
Secondary Outcome Measure Information:
Title
Phases 1 and 2: Plasma Concentration of Debio 0123 and its Metabolite
Description
The pharmacokinetics (PK) of Debio-0123 and its metabolite will be evaluated in plasma.
Time Frame
Phase 1: Predose and at multiple timepoints up to 8 hours post dose up to Day 15 of Cycle 1 (Arm A) and up to Day 37 (Arm B); Phase 2: Predose and at multiple timepoints up to 4 hours post dose up to Day 15 of Cycle 1 (Cycle=28 days)]
Title
Phases 1 and 2: Percentage of Participants With Best Overall Response (BOR) Assessed As Per Response Assessment in Neuro-oncology (RANO) Criteria
Time Frame
From the start of study treatment until disease progression or end of study (up to approximately 54 months)
Title
Phases 1 and 2: Percentage of Participants With Objective Response (OR) Assessed As Per RANO Criteria
Time Frame
Up to end of study (approximately 54 months)
Title
Phases 1 and 2: Percentage of Participants With Disease Control (DC) Assessed As Per RANO Criteria
Time Frame
From the start of study treatment until disease progression or end of study (up to approximately 54 months)
Title
Phases 1 and 2: Duration of Response (DOR) Assessed As Per RANO Criteria
Time Frame
Up to disease progression or end of study (up to approximately 54 months)
Title
Phases 1 and 2: Progression Free Survival (PFS) Assessed As Per RANO Criteria
Time Frame
From the start of study treatment until disease progression or death or end of study (up to approximately 54 months)
Title
Phase 1: Plasma Concentration of Temozolomide
Description
The PK of temozolomide will be evaluated in plasma.
Time Frame
Phase 1: Predose and at multiple timepoints up to 7 hours post dose up to Day 5 of Cycle 1 (Arm A) and up to Day 37 (Arm B)
Title
Phase 2: Number of Participants With At Least One TEAE
Time Frame
Up to 30 days after the end of treatment (up to approximately 26 months)
Title
Phase 2: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and ECG Parameters
Time Frame
Up to 30 days after the end of treatment (up to approximately 26 months)
Title
Phase 2: Change From Baseline in KPS Score
Description
KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.
Time Frame
Until disease progression or end of study (approximately 54 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Screening Inclusion Criteria for Phase 1 Arm A 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 Arm A and Phase 2: A maximum of 1 (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). 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: GBM Isocitrate dehydrogenase (IDH)-wildtype Grade 4 (based on WHO 2021), which may include secondary GBMs (i.e., those that progress from low-grade gliomas). Astrocytoma, IDH-mutant, Grade 3 (based on WHO 2021). Additional specific inclusion criteria for Phase 1 Arm B: 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). KPS ≥70. Additional specific inclusion criteria for Phase 2: Participants must have a histopathologically proven diagnosis of GBM, IDH-wildtype Grade 4 (based on WHO 2021). 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 based on WHO 2021. Exclusion Criteria for Phases 1 and 2: Known contraindication 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%. Specific exclusion criteria for Phase 1 Arm A and Phase 2: Prior treatment with bevacizumab or with other vascular endothelial growth factor (VEGF) inhibitors or VEGF-receptor signaling inhibitors. Prior TMZ-related hematological event leading to discontinuation of TMZ during the concurrent chemoradiotherapy. Specific exclusion criteria for Phase 1 Arm B: 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. Exclusion criteria for 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 line. [Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.]
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Debiopharm International S.A
Phone
+41 21 321 01 11
Email
clinicaltrials@debiopharm.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Debiopharm International SA
Official's Role
Study Director
Facility Information:
Facility Name
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
South Texas Accelerated Research Therapeutics (START)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Clinica Universidad de Navarra (CUN)
City
Madrid
ZIP/Postal Code
28027
Country
Spain
Individual Site Status
Recruiting
Facility Name
South Texas Accelerated Research Therapeutics (START)
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Name
Clinica Universidad de Navarra (CUN)
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Universitaetsspital Zuerich
City
Zuerich
ZIP/Postal Code
CH-8091
Country
Switzerland
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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