Solid Tumors
Conditions
Brief summary
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.
Interventions
DRUGPart A: Debio 1143
Adaptive doses of Debio1143 oral capsules, between 50 and 400 mg until the recommended dose (RD) is determined.
DRUGPaclitaxel
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.
DRUGCarboplatin
Carboplatin standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle.
DRUGPart B: Debio 1143
RD of Debio1143 oral capsules, once daily for five consecutive days starting on day 1 or 2 of each 21-day treatment cycle.
Sponsors
Debiopharm International SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meets protocol-specified criteria for qualification and contraception * Is willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related to food, drink and medications * Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures
Exclusion criteria
* Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters * Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: 1. the safety or well-being of the participant or study staff; 2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding); or 3. the analysis of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of participants with dose-limiting toxicities | up to 18 weeks | Categories: each Debio 1143 dose level and overall |
| 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 | up to 18 weeks + 28 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of participants with change in electrocardiogram (ECG) | up to 18 weeks | Categories: each Debio 1143 dose level and overall |
| Part A: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS) | up to 18 weeks | Categories: each Debio 1143 dose level and overall |
| Part B: Number of participants with change in vital signs | up to 18 weeks | Categories: each indication at the recommended dose (RD) |
| Part B: Number of participants with change in electrocardiogram (ECG) | up to 18 weeks | Categories: each indication at the recommended dose (RD) |
| Part B: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS) | up to 18 weeks | Categories: each indication at the recommended dose (RD) |
| Part A: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria | up to 18 weeks | Categories: each Debio 1143 dose level and overall |
| Part B: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria | up to 18 weeks | Categories: each indication at the RD |
| Part A: Percentage of participants with treatment discontinuations due to AEs and SAEs | up to 18 weeks + 28 days | Categories: each Debio 1143 dose level and overall |
| Part B: Percentage of participants with treatment discontinuations due to AEs and SAEs | up to 18 weeks + 28 days | Categories: each indication at the RD |
| Part A: Number of participants with change in left ventricular ejection fraction (LVEF) | up to 18 weeks | Categories: each Debio 1143 dose level and overall |
| Part B: Number of participants with change in left ventricular ejection fraction (LVEF) | up to 18 weeks | Categories: each indication at the RD |
| Part A: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response | up to 18 weeks | Categories: each Debio 1143 dose level and overall |
| Part B: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response | up to 18 weeks | Categories: each indication at the RD |
| Part A: Percentage of participants with progression-free survival (PFS) at 6 months | at 6 months | Categories: each Debio 1143 dose level and overall |
| Part B: Percentage of participants with progression-free survival (PFS) at 6 months | at 6 months | Categories: each indication at the RD |
| Part A: Percentage of participants with survival at 1 year | at 12 months | Categories: each Debio 1143 dose level and overall |
| Part B: Percentage of participants with survival at 1 year | at 12 months | Categories: each indication at the RD |
| Part B: Maximum concentration (Cmax) in the pharmacokinetic (PK) subset | up to 18 weeks | 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 |
| Part B: Lowest concentration before the next dose (Ctrough) of Debio 1143 in the PK subset | up to 18 weeks | Categories: alone and in combination with chemotherapy |
| Part B: Time to maximum concentration (tmax) in the PK subset | up to 18 weeks | 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 |
| Part B: Area under the concentration versus time curve from the beginning to a point in time (AUC0-t) in the PK subset | up to 18 weeks | 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 |
| Part B: Area under the concentration versus time curve extrapolated to infinity (AUC∞) in the PK subset | up to 18 weeks | 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 |
| Part B: Terminal rate constant (λz) in the PK subset | up to 18 weeks | 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 |
| Part B: Apparent terminal half-life (t½) in the PK subset | up to 18 weeks | 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 |
| Part B: Mean residence time (MRT) in the PK subset | up to 18 weeks | 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 |
| Part B: Apparent clearance (CL/F) of Debio 1143 in the PK subset | up to 18 weeks | Categories: alone and in combination with chemotherapy |
| Part B: Apparent volume of distribution during the terminal phase (Vz/F) of Debio 1143 in the PK subset | up to 18 weeks | Categories: alone and in combination with chemotherapy |
| Part B: Total amount of Debio 1143 excreted in urine (Ae) in the PK subset | up to 18 weeks | Categories: alone and in combination with chemotherapy |
| Part B: Total amount of Debio 1143 excreted in urine in the first 8 hours (Ae0-8) in the PK subset | up to 18 weeks | Categories: alone and in combination with chemotherapy |
| Part B: Total amount of Debio 1143 excreted in urine between 8 and 24 hours (Ae8-24) in the PK subset | up to 18 weeks | Categories: alone and in combination with chemotherapy |
| Part B: Renal clearance calculated as Ae/AUC∞ (CLR) of Debio 1143 in the PK subset | up to 18 weeks | Categories: alone and in combination with chemotherapy |
| Part B: Fraction of the dose excreted in urine calculated as Ae/dose (fe) of Debio 1143 in the PK subset | up to 18 weeks | Categories: alone and in combination with chemotherapy |
| Part B: Area under the concentration versus time curve in the first 12 hours (AUC0-12) in the PK subset | up to 18 weeks | 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 |
| Part B: Total body clearance (CL) in the PK subset | up to 18 weeks | 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 |
| Part B: Volume of distribution at steady-state (Vss) in the PK subset | up to 18 weeks | 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 |
| Part B: Mean Residence Area under the concentration versus time curve (MR,AUC) in the PK subset | up to 18 weeks | 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 |
| 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 | up to 18 weeks + 28 days | Categories: each Debio 1143 dose level and overall |
| Part B: Platinum Refraction (PtR) in ovarian cancer participants included in the PK subset | up to 18 weeks | 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 |
| Part B: Cmax in patients other than the PK subset | up to 18 weeks | 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 |
| Part B: Concentration observed at time n (Cn) following Debio 1143 administration in patients other than the PK subset | up to 18 weeks | 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 |
| Part B: Mean Residence Maximum Concentration (MR,Cmax) in the PK subset | up to 18 weeks | 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 |
| Part A: Number of participants with change in vital signs | up to 18 weeks | Categories: each Debio 1143 dose level and overall |
Countries
France
Outcome results
None listed