The primary purpose of part 1 (dose escalation) of this study is to identify the recommended dose and to characterize the safety and tolerability of Debio 0123 in combination with carboplatin and etoposide. The primary purpose of part 2 (dose expansion) of this study is to characterize the safety and tolerability of Debio 0123 at the recommended dose when administered in combination with carboplatin and etoposide.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Administered as capsules.
Administered as IV infusion.
Administered as IV infusion.
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
Hospital Universitario de A Coruna
A Coruña, Spain
Hospital Universitario Vall d'Hebron
Barcelona, Spain
Institut Catala D'Oncologia - Badalona
Barcelona, Spain
Clinica Universidad de Navarra
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario HM Sanchinarro. START Madrid - Centro Integral Oncológico Clara Campal (CIOCC)
Madrid, Spain
NEXT Oncology Madrid
Madrid, Spain
Hospital Quironsalud Malaga
Málaga, Spain
Hospital Clinico Universitario de Valencia
Valencia, Spain
Part 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Time frame: Cycle 1 (Cycle=21 days)
Parts 1 and 2: Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Approximately up to 44 months
Parts 1 and 2: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, Electrocardiogram (ECG), and Echocardiogram Parameters
Time frame: Approximately up to 44 months
Parts 1 and 2: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Time frame: Baseline up to approximately 44 months
Parts 1 and 2: Trough Concentration (Ctrough) of Debio 0123 and its Metabolite
Time frame: For Part 1: Predose from Day 2 to Day 11 of Cycle 1; For Part 2: Predose from Day 3 to Day 10 of Cycle 1 and only Day 8 of subsequent cycles up to Cycle 5 (Cycle=21 days)
Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Debio 0123 and its Metabolite
Time frame: For Part 1: Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days); For Part 2: Will be derived from the population Pharmacokinetic (PK) model using the sparse samples collected
Parts 1 and 2: Area Under the Concentration Curve Over 24 hours (AUC24h) of Debio 0123 and its Metabolite
Time frame: For Part 1: Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days); For Part 2: Will be derived from the population PK model using the sparse samples collected
Part 1: Time to Maximum Plasma Concentration (tmax) of Debio 0123 and its Metabolite
Time frame: Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days)
Part 1: Area Under the Concentration Curve up to the Last Measurable Concentration (AUClast) of Debio 0123 and its Metabolite
Time frame: Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days)
Part 1: Area Under the Concentration Curve up to Infinity (AUCinf) of Debio 0123 and its Metabolite
Time frame: Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days)
Part 1: Apparent Terminal Half-life (t1/2) of Debio 0123 and its Metabolite
Time frame: Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days)
Part 1: Apparent Clearance (CL/F) of Debio 0123
Time frame: Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days)
Part 1: Apparent Volume of Distribution (Vd/F) of Debio 0123
Time frame: Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days)
Part 1: Maximum Plasma Concentration (Cmax) of Etoposide
Time frame: Multiple timepoints from administration to post dose from Day 1 to Day 3 of Cycle 1 (Cycle=21 days)]
Part 1: Area Under the Concentration Curve Over 24 hours (AUC24h) of Etoposide
Time frame: Multiple timepoints post dose from Day 1 to Day 5 of Cycle 1 (Cycle=21 days)
Part 1: Trough Concentration (Ctrough) of Etoposide
Time frame: Predose from Day 2 to Day 5 of Cycle 1 (Cycle=21 days)
Part 1: Maximum Plasma Concentration (Cmax) of Carboplatin
Time frame: Multiple timepoints from administration up to 6 hours post dose on Day 1 of Cycle 1 (Cycle=21 days)
Parts 1 and 2: Percentage of Participants With Best Overall Response (BOR) Assessed as per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 Criteria
Time frame: From the start of study treatment until disease progression or end of study (up to approximately 44 months)
Parts 1 and 2: Percentage of Participants With Objective Response (OR) Assessed as per RECIST 1.1 Criteria
Time frame: Up to end of study (approximately 44 months)
Parts 1 and 2: Percentage of Participants With Disease Control (DC) Assessed as per RECIST 1.1 Criteria
Time frame: From the start of study treatment until disease progression or end of study (up to approximately 44 months)
Parts 1 and 2: Duration of Response (DOR) Assessed as per RECIST 1.1 Criteria
Time frame: Up to disease progression or end of study (approximately 44 months)
Parts 1 and 2: Progression Free Survival (PFS) Assessed as per RECIST 1.1 Criteria
Time frame: From the start of study treatment until disease progression or death or end of study (up to approximately 44 months)
Part 2: Overall Survival
Time frame: From the start of study treatment until death from any cause or end of study (up to approximately 44 months
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