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

Phase 1

Recruiting

• Conditions: Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype; Astrocytoma, Grade III
• Interventions: Drug: Debio 0123; Drug: Temozolomide; Radiation: Radiotherapy

• Registration Number: NCT05765812
• Lead 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-15
• Study First Submitted QC: 2023-03-09
• Study First Posted: 2023-03-13
• Study Start: 2023-05-15
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-20
• Primary Completion: 2028-09
• Study Completion: 2028-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1 (Dose Escalation): Arm A - Debio 0123 + Temozolomide	Debio 0123	Participants will receive intermittent Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years.
Phase 1 (Dose Expansion): Debio 0123 + Temozolomide	Debio 0123	Participants will receive Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years. Participants will receive one of the 2 selected doses for further investigation.
Phase 1 (Dose Escalation): Arm C - Debio 0123 + Temozolomide + Radiotherapy	Radiotherapy	Participants will receive intermittent Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.
Phase 1 (Dose Escalation): Arm A - Debio 0123 + Temozolomide	Temozolomide	Participants will receive intermittent Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years.
Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy	Debio 0123	Participants will receive intermittent Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks. As per Protocol _V4.0 Arm B has been permanently halted.
Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy	Radiotherapy	Participants will receive intermittent Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks. As per Protocol _V4.0 Arm B has been permanently halted.
Phase 2: Debio 0123 RD + Temozolomide	Debio 0123	Participants will receive intermittent Debio 0123 RD along with TMZ in each 28-day cycle for up to 2 years.
Phase 1 (Dose Escalation): Arm C - Debio 0123 + Temozolomide + Radiotherapy	Debio 0123	Participants will receive intermittent Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.
Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy	Temozolomide	Participants will receive intermittent Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks. As per Protocol _V4.0 Arm B has been permanently halted.
Phase 1 (Dose Escalation): Arm C - Debio 0123 + Temozolomide + Radiotherapy	Temozolomide	Participants will receive intermittent Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.
Phase 1 (Dose Expansion): Debio 0123 + Temozolomide	Temozolomide	Participants will receive Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years. Participants will receive one of the 2 selected doses for further investigation.
Phase 2: Debio 0123 RD + Temozolomide	Temozolomide	Participants will receive intermittent Debio 0123 RD along with TMZ in each 28-day cycle for up to 2 years.

Primary Outcome Measures

Name	Time	Method
Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-limiting Toxicities (DLTs)	Phase 1: Arm A: Cycle 1 (Cycle=28 days); Arms B and C: Up to approximately 1.8 months
Phase 1 (Dose Expansion): Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)	Up to approximately 26 months
Phase 1 (Dose Expansion): Plasma Concentration of Debio 0123 and its Metabolite	Predose and at multiple timepoints up to 6 hours post dose up to Day 15 of Cycle 1 (Cycle=28 days)
Phase 2: Overall Survival (OS)	From the start of study treatment until death from any cause or end of study (up to approximately 66 months)
Phase 1 (Dose Escalation): Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)	Up to 30 days after the end of treatment (Arm A: Up to approximately 26 months and Arms B and C: Up to approximately 3.5 months)
Phase 1 (Dose Escalation): Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, Electrocardiogram (ECG), and Echocardiogram (ECHO) Parameters	Up to 30 days after the end of treatment (Arm A: Up to approximately 26 months and Arms B and C: Up to approximately 3.5 months)
Phase 1 (Dose Escalation): Change From Baseline in Karnofsky Performance Status (KPS) Score	Until disease progression or end of study (approximately 66 months)	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 1 (Dose Expansion): Change from Baseline in Tumor Size Assessed by Objective Response (OR) as per Response Assessment in Neuro-oncology (RANO) Criteria	From the start of study treatment until disease progression or end of study (up to approximately 66 months)
Phase 1 (Dose Expansion): Pharmacodynamic(s) PDy, Change from baseline in Phosphorylated Cell Division Cycle (pCDC2)	Predose and 4 to 6 hours post dose on Day 10 of Cycle 1 (Cycle=28 days)

Secondary Outcome Measures

Name	Time	Method
Phases 1 and 2: Percentage of Participants With Best Overall Response (BOR) Assessed As Per Response Assessment in Neuro-oncology (RANO) Criteria	From the start of study treatment until disease progression or end of study (up to approximately 66 months)
Phases 1 and 2: Percentage of Participants with Objective Response (OR) Assessed As Per RANO Criteria	Up to end of study (approximately 66 months)
Phase 1 (Dose Escalation): Plasma Concentration of Temozolomide	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 29 (Arm B and C)	The PK of temozolomide will be evaluated in plasma.
Phase 1 (Dose Expansion): Number of Participants With Clinically Significant Abnormalities In Laboratory, Vital Signs, ECG, and (ECHO Parameters)	Up to 30 days after the end of treatment (up to approximately 26 months)
Phase 1 (Dose Expansion): OS	From the start of study treatment until death from any cause or end of study (up to approximately 66 months)
Phase 2: Number of Participants With At Least One TEAE	Up to 30 days after the end of treatment (up to approximately 26 months)
Phases 1 and 2: Plasma Concentration of Debio 0123 and its Metabolite	Phase1(Dose Escalation):Predose, multiple timepoints upto 8hours postdose upto Day 15 of Cycle 1(Arm A) and upto Day 29(Arms B and C);Phase1(Dose expansion)andPhase2: Predose, multiple timepoints upto 4hours postdose upto Day 15 of Cycle1(Cycle=28 days)	The pharmacokinetics (PK) of Debio-0123 and its metabolite will be evaluated in plasma.
Phase 1 (Dose Expansion): Number of Participants With At Least one TEAE	Up to 30 days after the end of treatment (up to approximately 26 months)
Phase 1 (Dose Expansion): Change From Baseline in KPS Score	Until disease progression or end of study (approximately 66 months)	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: Change From Baseline in KPS Score	Until disease progression or end of study (approximately 66 months)	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: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and ECG Parameters	Up to 30 days after the end of treatment (up to approximately 26 months)
Phases 1 and 2: Percentage of Participants With Disease Control (DC) Assessed As Per RANO Criteria	From the start of study treatment until disease progression or end of study (up to approximately 66 months)
Phases 1 and 2: Duration of Response (DOR) Assessed As Per RANO Criteria	Up to disease progression or end of study (up to approximately 66 months)
Phases 1 and 2: Progression Free Survival (PFS) Assessed As Per RANO Criteria	From the start of study treatment until disease progression or death or end of study (up to approximately 66 months)

Trial Locations

Locations (10)

New York University Langone Medical Center; 🇺🇸 New York, New York, United States

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

South Texas Accelerated Research Therapeutics (START); 🇪🇸 Madrid, Spain

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Clinica Universidad de Navarra (CUN); 🇪🇸 Pamplona, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Universitaetsspital Zuerich; 🇨🇭 Zuerich, Switzerland