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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003676-40 | EudraCT Number |
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Part B was cancelled based on business decision
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Debio 1143 | Experimental | Eligible participants receive Part A: Debio 1143 once daily for 5 consecutive days in each 21-day treatment cycle according to dose escalation rules (in combination with Paclitaxel and Carboplatin standard of care) |
|
| Part B: Lung Cancer | Experimental | Participants with Lung Cancer receive Part B: Debio 1143 once daily for 5 consecutive days in each 21-day treatment cycle (in combination with Paclitaxel and Carboplatin standard of care) |
|
| Part B: Ovarian Cancer | Experimental | Participants with Ovarian Cancer receive Part B: Debio 1143 once daily for 5 consecutive days in each 21-day treatment cycle (in combination with Paclitaxel and Carboplatin standard of care) |
|
| Part B: Breast Cancer | Experimental | Participants with Breast Cancer receive Part B: Debio 1143 once daily for 5 consecutive days in each 21-day treatment cycle (in combination with Paclitaxel and Carboplatin standard of care) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Part A: Debio 1143 | Drug | Adaptive doses of Debio1143 oral capsules, between 50 and 400 mg until the recommended dose (RD) is determined. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Number of participants with dose-limiting toxicities | Categories: each Debio 1143 dose level and overall | 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 | up to 18 weeks + 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | up to 18 weeks + 28 days |
| Part A: Number of participants with change in vital signs |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Pierre Delord, MD | Institut Claudius Regaud, Toulouse, France | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Georges François Leclerc | Dijon | 21079 | France | |||
| Centre Léon Bérard |
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| Label | URL |
|---|---|
| Site Debiopharm SA | View source |
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| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| D016190 | Carboplatin |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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| Paclitaxel | Drug | 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 | Drug | Carboplatin standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle. |
|
| Part B: Debio 1143 | Drug | RD of Debio1143 oral capsules, once daily for five consecutive days starting on day 1 or 2 of each 21-day treatment cycle. |
|
Categories: each Debio 1143 dose level and overall |
| up to 18 weeks |
| Part A: Number of participants with change in electrocardiogram (ECG) | Categories: each Debio 1143 dose level and overall | 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 | up to 18 weeks |
| Part B: Number of participants with change in vital signs | Categories: each indication at the recommended dose (RD) | up to 18 weeks |
| Part B: Number of participants with change in electrocardiogram (ECG) | Categories: each indication at the recommended dose (RD) | 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) | 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 | 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 | 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 | 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 | 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 | up to 18 weeks |
| Part B: Number of participants with change in left ventricular ejection fraction (LVEF) | Categories: each indication at the RD | 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 | 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 | 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 | at 6 months |
| Part B: Percentage of participants with progression-free survival (PFS) at 6 months | Categories: each indication at the RD | at 6 months |
| Part A: Percentage of participants with survival at 1 year | Categories: each Debio 1143 dose level and overall | at 12 months |
| Part B: Percentage of participants with survival at 1 year | Categories: each indication at the RD | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | up to 18 weeks |
| Part B: Apparent clearance (CL/F) of Debio 1143 in the PK subset | Categories: alone and in combination with chemotherapy | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | up to 18 weeks |
| Lyon |
| 69008 |
| France |
| Institut Curie | Paris | 75248 | France |
| Institut Claudius Regaud | Toulouse | 31052 | France |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D056831 | Coordination Complexes |