Debio 1143 in Combination With Carboplatin and Paclitaxel in Patient With Advanced Solid Malignancies
- Registration Number
- NCT01930292
- Lead Sponsor
- Debiopharm International SA
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 31
- 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
-
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:
- the safety or well-being of the participant or study staff;
- the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding); or
- the analysis of results
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: Lung Cancer Carboplatin 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 A: Debio 1143 Paclitaxel 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: Ovarian Cancer Paclitaxel 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: Ovarian Cancer Carboplatin 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 A: Debio 1143 Carboplatin 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 Paclitaxel 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: Breast Cancer Paclitaxel 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) Part B: Breast Cancer Carboplatin 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)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Part B: Number of participants with change in electrocardiogram (ECG) up to 18 weeks Categories: each indication at the recommended dose (RD)
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 A: Number of participants with change in vital signs up to 18 weeks Categories: each Debio 1143 dose level and overall
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 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: 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 Eastern Cooperative Oncology Group (ECOG) performance status (PS) up to 18 weeks Categories: each indication at the recommended dose (RD)
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 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 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
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Trial Locations
- Locations (4)
Centre Georges François Leclerc
🇫🇷Dijon, France
Institut Curie
🇫🇷Paris, France
Centre Léon Bérard
🇫🇷Lyon, France
Institut Claudius Regaud
🇫🇷Toulouse, France