Clinical trial NCT01930292: Debio 1143 in Combination With Carboplatin and Paclitaxel in Patient With Advanced Solid Malignancies
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2013-08-28
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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:

  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

Primary outcomes:
measure: Part A: Number of participants with dose-limiting toxicities
timeFrame: up to 18 weeks
measure: 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
timeFrame: up to 18 weeks + 28 days
Secondary outcomes:
measure: 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
timeFrame: up to 18 weeks + 28 days
measure: Part A: Number of participants with change in vital signs
timeFrame: up to 18 weeks
measure: Part A: Number of participants with change in electrocardiogram (ECG)
timeFrame: up to 18 weeks
measure: Part A: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS)
timeFrame: up to 18 weeks
measure: Part B: Number of participants with change in vital signs
timeFrame: up to 18 weeks
measure: Part B: Number of participants with change in electrocardiogram (ECG)
timeFrame: up to 18 weeks
measure: Part B: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS)
timeFrame: up to 18 weeks
measure: Part A: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria
timeFrame: up to 18 weeks
measure: Part B: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria
timeFrame: up to 18 weeks
measure: Part A: Percentage of participants with treatment discontinuations due to AEs and SAEs
timeFrame: up to 18 weeks + 28 days
measure: Part B: Percentage of participants with treatment discontinuations due to AEs and SAEs
timeFrame: up to 18 weeks + 28 days
measure: Part A: Number of participants with change in left ventricular ejection fraction (LVEF)
timeFrame: up to 18 weeks
measure: Part B: Number of participants with change in left ventricular ejection fraction (LVEF)
timeFrame: up to 18 weeks
measure: Part A: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response
timeFrame: up to 18 weeks
measure: Part B: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response
timeFrame: up to 18 weeks
measure: Part A: Percentage of participants with progression-free survival (PFS) at 6 months
timeFrame: at 6 months
measure: Part B: Percentage of participants with progression-free survival (PFS) at 6 months
timeFrame: at 6 months
measure: Part A: Percentage of participants with survival at 1 year
timeFrame: at 12 months
measure: Part B: Percentage of participants with survival at 1 year
timeFrame: at 12 months
measure: Part B: Maximum concentration (Cmax) in the pharmacokinetic (PK) subset
timeFrame: up to 18 weeks
measure: Part B: Lowest concentration before the next dose (Ctrough) of Debio 1143 in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Time to maximum concentration (tmax) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Area under the concentration versus time curve from the beginning to a point in time (AUC0-t) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Area under the concentration versus time curve extrapolated to infinity (AUC∞) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Terminal rate constant (λz) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Apparent terminal half-life (t½) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Mean residence time (MRT) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Apparent clearance (CL/F) of Debio 1143 in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Apparent volume of distribution during the terminal phase (Vz/F) of Debio 1143 in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Total amount of Debio 1143 excreted in urine (Ae) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Total amount of Debio 1143 excreted in urine in the first 8 hours (Ae0-8) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Total amount of Debio 1143 excreted in urine between 8 and 24 hours (Ae8-24) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Renal clearance calculated as Ae/AUC∞ (CLR) of Debio 1143 in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Fraction of the dose excreted in urine calculated as Ae/dose (fe) of Debio 1143 in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Area under the concentration versus time curve in the first 12 hours (AUC0-12) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Total body clearance (CL) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Volume of distribution at steady-state (Vss) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Mean Residence Area under the concentration versus time curve (MR,AUC) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Mean Residence Maximum Concentration (MR,Cmax) in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Platinum Refraction (PtR) in ovarian cancer participants included in the PK subset
timeFrame: up to 18 weeks
measure: Part B: Cmax in patients other than the PK subset
timeFrame: up to 18 weeks
measure: Part B: Concentration observed at time n (Cn) following Debio 1143 administration in patients other than the PK subset
timeFrame: up to 18 weeks
Other outcomes:
Locations:
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lyon
country: France
facility: Centre Léon Bérard
city: Paris
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: Institut Claudius Regaud
Study officials:
affiliation: Institut Claudius Regaud, Toulouse, France
name: Jean-Pierre Delord, MD
role: STUDY_CHAIR
References: