Debio 1143 in Combination With Carboplatin and Paclitaxel in Patient With Advanced Solid Malignancies

Solid Tumors Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01930292
• Other study ID #: Debio 1143-103
• Secondary ID: 2012-003676-40
• Status: Terminated
• Phase: Phase 1
• First received: June 21, 2013
• Last updated: March 23, 2016
• Start date: April 2013
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Part A: Debio 1143
Adaptive doses of Debio1143 oral capsules, between 50 and 400 mg until the recommended dose (RD) is determined.
• Paclitaxel
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
Carboplatin standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle.
• Part 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.

Locations

Country	Name	City	State
France	Centre Georges François Leclerc	Dijon
France	Centre Léon Bérard	Lyon
France	Institut Curie	Paris
France	Institut Claudius Regaud	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Number of participants with dose-limiting toxicities	Categories: each Debio 1143 dose level and overall	up to 18 weeks	No
Primary	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	No
Secondary	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	No
Secondary	Part A: Number of participants with change in vital signs	Categories: each Debio 1143 dose level and overall	up to 18 weeks	No
Secondary	Part A: Number of participants with change in electrocardiogram (ECG)	Categories: each Debio 1143 dose level and overall	up to 18 weeks	No
Secondary	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	No
Secondary	Part B: Number of participants with change in vital signs	Categories: each indication at the recommended dose (RD)	up to 18 weeks	No
Secondary	Part B: Number of participants with change in electrocardiogram (ECG)	Categories: each indication at the recommended dose (RD)	up to 18 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Part B: Number of participants with change in left ventricular ejection fraction (LVEF)	Categories: each indication at the RD	up to 18 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	Part A: Percentage of participants with progression-free survival (PFS) at 6 months	Categories: each Debio 1143 dose level and overall	at 6 months	No
Secondary	Part B: Percentage of participants with progression-free survival (PFS) at 6 months	Categories: each indication at the RD	at 6 months	No
Secondary	Part A: Percentage of participants with survival at 1 year	Categories: each Debio 1143 dose level and overall	at 12 months	No
Secondary	Part B: Percentage of participants with survival at 1 year	Categories: each indication at the RD	at 12 months	No
Secondary	Part B: Maximum concentration (Cmax) in the pharmacokinetic (PK) subset	Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	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	No
Secondary	Part B: Time to maximum concentration (tmax) in the PK subset	Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	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, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Area under the concentration versus time curve extrapolated to infinity (AUC8) in the PK subset	Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Terminal rate constant (?z) in the PK subset	Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Apparent terminal half-life (t½) in the PK subset	Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Mean residence time (MRT) in the PK subset	Categories: Debio 1143 alone; Debio 1143 when administered with paclitaxel and carboplatin; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Apparent clearance (CL/F) of Debio 1143 in the PK subset	Categories: alone and in combination with chemotherapy	up to 18 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Part B: Renal clearance calculated as Ae/AUC8 (CLR) of Debio 1143 in the PK subset	Categories: alone and in combination with chemotherapy	up to 18 weeks	No
Secondary	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	No
Secondary	Part B: Area under the concentration versus time curve in the first 12 hours (AUC0-12) in the PK subset	Categories: paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Total body clearance (CL) in the PK subset	Categories: paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Volume of distribution at steady-state (Vss) in the PK subset	Categories: paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Mean Residence Area under the concentration versus time curve (MR,AUC) in the PK subset	Categories: paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Mean Residence Maximum Concentration (MR,Cmax) in the PK subset	Categories: paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Platinum Refraction (PtR) in ovarian cancer participants included in the PK subset	Categories: paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Cmax in patients other than the PK subset	Categories: paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No
Secondary	Part B: Concentration observed at time n (Cn) following Debio 1143 administration in patients other than the PK subset	Categories: paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered as chemotherapy alone; paclitaxel, 6aOH-paclitaxel (metabolite), and carboplatin (total and free Pt) when administered in combination with Debio 1143	up to 18 weeks	No

External Links

•   Site Debiopharm SA