This is a two-part trial in patients with squamous non-small cell lung cancer (NSCLC), platinum (Pt)-refractory ovarian cancer, and basal-like/claudin low triple negative breast cancer (TNBC). The primary objective of Part A is to determine the maximum tolerated dose (MTD) of Debio 1143 when administered to these patients in combination with full doses of paclitaxel and carboplatin. The primary objective of Part B is to consolidate the safety profile of the recommended dose of Debio 1143 when administered to these patients in combination with full doses of paclitaxel and carboplatin.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Adaptive doses of Debio1143 oral capsules, between 50 and 400 mg until the recommended dose (RD) is determined.
Paclitaxel standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle, after pre-medication to prevent severe hypersensitivity reactions.
Carboplatin standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle.
RD of Debio1143 oral capsules, once daily for five consecutive days starting on day 1 or 2 of each 21-day treatment cycle.
Centre Georges François Leclerc
Dijon, France
Centre Léon Bérard
Lyon, France
Institut Curie
Paris, France
Institut Claudius Regaud
Toulouse, France
Part A: Number of participants with dose-limiting toxicities
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks
Part B: Percentage of participants with adverse events (AEs) and serious AEs (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria
Time frame: up to 18 weeks + 28 days
Part A: Percentage of participants with AEs and serious adverse events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks + 28 days
Part A: Number of participants with change in vital signs
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks
Part A: Number of participants with change in electrocardiogram (ECG)
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks
Part A: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS)
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks
Part B: Number of participants with change in vital signs
Categories: each indication at the recommended dose (RD)
Time frame: up to 18 weeks
Part B: Number of participants with change in electrocardiogram (ECG)
Categories: each indication at the recommended dose (RD)
Time frame: up to 18 weeks
Part B: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS)
Categories: each indication at the recommended dose (RD)
Time frame: up to 18 weeks
Part A: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks
Part B: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria
Categories: each indication at the RD
Time frame: up to 18 weeks
Part A: Percentage of participants with treatment discontinuations due to AEs and SAEs
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks + 28 days
Part B: Percentage of participants with treatment discontinuations due to AEs and SAEs
Categories: each indication at the RD
Time frame: up to 18 weeks + 28 days
Part A: Number of participants with change in left ventricular ejection fraction (LVEF)
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks
Part B: Number of participants with change in left ventricular ejection fraction (LVEF)
Categories: each indication at the RD
Time frame: up to 18 weeks
Part A: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response
Categories: each Debio 1143 dose level and overall
Time frame: up to 18 weeks
Part B: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response
Categories: each indication at the RD
Time frame: up to 18 weeks
Part A: Percentage of participants with progression-free survival (PFS) at 6 months
Categories: each Debio 1143 dose level and overall
Time frame: at 6 months
Part B: Percentage of participants with progression-free survival (PFS) at 6 months
Categories: each indication at the RD
Time frame: at 6 months
Part A: Percentage of participants with survival at 1 year
Categories: each Debio 1143 dose level and overall
Time frame: at 12 months
Part B: Percentage of participants with survival at 1 year
Categories: each indication at the RD
Time frame: at 12 months
Part B: Maximum concentration (Cmax) in the pharmacokinetic (PK) subset
Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Lowest concentration before the next dose (Ctrough) of Debio 1143 in the PK subset
Categories: alone and in combination with chemotherapy
Time frame: up to 18 weeks
Part B: Time to maximum concentration (tmax) in the PK subset
Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Area under the concentration versus time curve from the beginning to a point in time (AUC0-t) in the PK subset
Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Area under the concentration versus time curve extrapolated to infinity (AUC∞) in the PK subset
Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Terminal rate constant (λz) in the PK subset
Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Apparent terminal half-life (t½) in the PK subset
Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Mean residence time (MRT) in the PK subset
Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Apparent clearance (CL/F) of Debio 1143 in the PK subset
Categories: alone and in combination with chemotherapy
Time frame: up to 18 weeks
Part B: Apparent volume of distribution during the terminal phase (Vz/F) of Debio 1143 in the PK subset
Categories: alone and in combination with chemotherapy
Time frame: up to 18 weeks
Part B: Total amount of Debio 1143 excreted in urine (Ae) in the PK subset
Categories: alone and in combination with chemotherapy
Time frame: up to 18 weeks
Part B: Total amount of Debio 1143 excreted in urine in the first 8 hours (Ae0-8) in the PK subset
Categories: alone and in combination with chemotherapy
Time frame: up to 18 weeks
Part B: Total amount of Debio 1143 excreted in urine between 8 and 24 hours (Ae8-24) in the PK subset
Categories: alone and in combination with chemotherapy
Time frame: up to 18 weeks
Part B: Renal clearance calculated as Ae/AUC∞ (CLR) of Debio 1143 in the PK subset
Categories: alone and in combination with chemotherapy
Time frame: up to 18 weeks
Part B: Fraction of the dose excreted in urine calculated as Ae/dose (fe) of Debio 1143 in the PK subset
Categories: alone and in combination with chemotherapy
Time frame: up to 18 weeks
Part B: Area under the concentration versus time curve in the first 12 hours (AUC0-12) in the PK subset
Categories: paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Total body clearance (CL) in the PK subset
Categories: paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Volume of distribution at steady-state (Vss) in the PK subset
Categories: paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Mean Residence Area under the concentration versus time curve (MR,AUC) in the PK subset
Categories: paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Mean Residence Maximum Concentration (MR,Cmax) in the PK subset
Categories: paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Platinum Refraction (PtR) in ovarian cancer participants included in the PK subset
Categories: paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Cmax in patients other than the PK subset
Categories: paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
Part B: Concentration observed at time n (Cn) following Debio 1143 administration in patients other than the PK subset
Categories: paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6αOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143
Time frame: up to 18 weeks
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