A Phase I Study to Evaluate the Safety and Determine the Maximum Tolerated Dose (MTD) of Debio 1143 Combined With Carboplatin and Paclitaxel in Patients With Squamous Non-Small Cell Lung Cancer (NSCLC), Platinum-refractory Ovarian Cancer, and Basal-like/Claudin Low Triple Negative Breast Cancer (TNBC)
Overview
- Phase
- Phase 1
- Intervention
- Paclitaxel
- Conditions
- Solid Tumors
- Sponsor
- Debiopharm International SA
- Enrollment
- 31
- Locations
- 4
- Primary Endpoint
- Part A: Number of participants with dose-limiting toxicities
- Status
- Terminated
- Last Updated
- 10 years ago
Overview
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.
Investigators
Eligibility Criteria
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:
- •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
Arms & Interventions
Part A: Debio 1143
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)
Intervention: Paclitaxel
Part A: Debio 1143
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)
Intervention: Carboplatin
Part B: Lung Cancer
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)
Intervention: Paclitaxel
Part B: Lung Cancer
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)
Intervention: Carboplatin
Part B: Ovarian Cancer
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)
Intervention: Paclitaxel
Part B: Ovarian Cancer
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)
Intervention: Carboplatin
Part B: Breast Cancer
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)
Intervention: Paclitaxel
Part B: Breast Cancer
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)
Intervention: Carboplatin
Outcomes
Primary Outcomes
Part A: Number of participants with dose-limiting toxicities
Time Frame: 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
Time Frame: up to 18 weeks + 28 days
Secondary Outcomes
- Part B: Number of participants with change in electrocardiogram (ECG)(up to 18 weeks)
- 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)
- Part A: Number of participants with change in vital signs(up to 18 weeks)
- Part A: Number of participants with change in electrocardiogram (ECG)(up to 18 weeks)
- Part A: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS)(up to 18 weeks)
- Part A: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria(up to 18 weeks)
- Part B: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria(up to 18 weeks)
- Part A: Percentage of participants with treatment discontinuations due to AEs and SAEs(up to 18 weeks + 28 days)
- Part B: Number of participants with change in vital signs(up to 18 weeks)
- Part B: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS)(up to 18 weeks)
- Part B: Percentage of participants with treatment discontinuations due to AEs and SAEs(up to 18 weeks + 28 days)
- Part A: Number of participants with change in left ventricular ejection fraction (LVEF)(up to 18 weeks)
- Part B: Number of participants with change in left ventricular ejection fraction (LVEF)(up to 18 weeks)
- Part A: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response(up to 18 weeks)
- Part B: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response(up to 18 weeks)
- Part A: Percentage of participants with progression-free survival (PFS) at 6 months(at 6 months)
- Part B: Percentage of participants with progression-free survival (PFS) at 6 months(at 6 months)
- Part A: Percentage of participants with survival at 1 year(at 12 months)
- Part B: Percentage of participants with survival at 1 year(at 12 months)
- Part B: Maximum concentration (Cmax) in the pharmacokinetic (PK) subset(up to 18 weeks)
- Part B: Lowest concentration before the next dose (Ctrough) of Debio 1143 in the PK subset(up to 18 weeks)
- Part B: Total amount of Debio 1143 excreted in urine (Ae) in the PK subset(up to 18 weeks)
- Part B: Time to maximum concentration (tmax) in the PK subset(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(up to 18 weeks)
- Part B: Area under the concentration versus time curve extrapolated to infinity (AUC∞) in the PK subset(up to 18 weeks)
- Part B: Terminal rate constant (λz) in the PK subset(up to 18 weeks)
- Part B: Apparent terminal half-life (t½) in the PK subset(up to 18 weeks)
- Part B: Mean residence time (MRT) in the PK subset(up to 18 weeks)
- Part B: Apparent clearance (CL/F) of Debio 1143 in the PK subset(up to 18 weeks)
- Part B: Apparent volume of distribution during the terminal phase (Vz/F) of Debio 1143 in the PK subset(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(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(up to 18 weeks)
- Part B: Renal clearance calculated as Ae/AUC∞ (CLR) of Debio 1143 in the PK subset(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(up to 18 weeks)
- Part B: Area under the concentration versus time curve in the first 12 hours (AUC0-12) in the PK subset(up to 18 weeks)
- Part B: Total body clearance (CL) in the PK subset(up to 18 weeks)
- Part B: Volume of distribution at steady-state (Vss) in the PK subset(up to 18 weeks)
- Part B: Mean Residence Area under the concentration versus time curve (MR,AUC) in the PK subset(up to 18 weeks)
- Part B: Mean Residence Maximum Concentration (MR,Cmax) in the PK subset(up to 18 weeks)
- Part B: Platinum Refraction (PtR) in ovarian cancer participants included in the PK subset(up to 18 weeks)
- Part B: Cmax in patients other than the PK subset(up to 18 weeks)
- Part B: Concentration observed at time n (Cn) following Debio 1143 administration in patients other than the PK subset(up to 18 weeks)