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

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ClinicalTrials.gov Identifier: NCT01930292
Recruitment Status : Terminated (Part B was cancelled based on business decision)
First Posted : August 28, 2013
Last Update Posted : March 24, 2016
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Part A: Debio 1143 Drug: Paclitaxel Drug: Carboplatin Drug: Part B: Debio 1143 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : April 2013
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016


Arm Intervention/treatment
Experimental: 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)
Drug: Part A: Debio 1143
Adaptive doses of Debio1143 oral capsules, between 50 and 400 mg until the recommended dose (RD) is determined.

Drug: 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.

Drug: Carboplatin
Carboplatin standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle.

Experimental: 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)
Drug: 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.

Drug: Carboplatin
Carboplatin standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle.

Drug: 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.

Experimental: 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)
Drug: 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.

Drug: Carboplatin
Carboplatin standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle.

Drug: 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.

Experimental: 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)
Drug: 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.

Drug: Carboplatin
Carboplatin standard of care, intravenous (IV), once on day 1 or 2 of each 21-day treatment cycle.

Drug: 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.




Primary Outcome Measures :
  1. Part A: Number of participants with dose-limiting toxicities [ Time Frame: up to 18 weeks ]
    Categories: each Debio 1143 dose level and overall

  2. 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 Outcome Measures :
  1. 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 [ Time Frame: up to 18 weeks + 28 days ]
    Categories: each Debio 1143 dose level and overall

  2. Part A: Number of participants with change in vital signs [ Time Frame: up to 18 weeks ]
    Categories: each Debio 1143 dose level and overall

  3. Part A: Number of participants with change in electrocardiogram (ECG) [ Time Frame: up to 18 weeks ]
    Categories: each Debio 1143 dose level and overall

  4. Part A: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS) [ Time Frame: up to 18 weeks ]
    Categories: each Debio 1143 dose level and overall

  5. Part B: Number of participants with change in vital signs [ Time Frame: up to 18 weeks ]
    Categories: each indication at the recommended dose (RD)

  6. Part B: Number of participants with change in electrocardiogram (ECG) [ Time Frame: up to 18 weeks ]
    Categories: each indication at the recommended dose (RD)

  7. Part B: Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status (PS) [ Time Frame: up to 18 weeks ]
    Categories: each indication at the recommended dose (RD)

  8. Part A: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria [ Time Frame: up to 18 weeks ]
    Categories: each Debio 1143 dose level and overall

  9. Part B: Percentage of participants with incidence of laboratory abnormalities according to NCI-CTCAE criteria [ Time Frame: up to 18 weeks ]
    Categories: each indication at the RD

  10. Part A: Percentage of participants with treatment discontinuations due to AEs and SAEs [ Time Frame: up to 18 weeks + 28 days ]
    Categories: each Debio 1143 dose level and overall

  11. Part B: Percentage of participants with treatment discontinuations due to AEs and SAEs [ Time Frame: up to 18 weeks + 28 days ]
    Categories: each indication at the RD

  12. Part A: Number of participants with change in left ventricular ejection fraction (LVEF) [ Time Frame: up to 18 weeks ]
    Categories: each Debio 1143 dose level and overall

  13. Part B: Number of participants with change in left ventricular ejection fraction (LVEF) [ Time Frame: up to 18 weeks ]
    Categories: each indication at the RD

  14. Part A: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response [ Time Frame: up to 18 weeks ]
    Categories: each Debio 1143 dose level and overall

  15. Part B: Number of participants with tumour response: disease control, change in tumour size from baseline and overall response [ Time Frame: up to 18 weeks ]
    Categories: each indication at the RD

  16. Part A: Percentage of participants with progression-free survival (PFS) at 6 months [ Time Frame: at 6 months ]
    Categories: each Debio 1143 dose level and overall

  17. Part B: Percentage of participants with progression-free survival (PFS) at 6 months [ Time Frame: at 6 months ]
    Categories: each indication at the RD

  18. Part A: Percentage of participants with survival at 1 year [ Time Frame: at 12 months ]
    Categories: each Debio 1143 dose level and overall

  19. Part B: Percentage of participants with survival at 1 year [ Time Frame: at 12 months ]
    Categories: each indication at the RD

  20. Part B: Maximum concentration (Cmax) in the pharmacokinetic (PK) subset [ Time Frame: 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

  21. Part B: Lowest concentration before the next dose (Ctrough) of Debio 1143 in the PK subset [ Time Frame: up to 18 weeks ]
    Categories: alone and in combination with chemotherapy

  22. Part B: Time to maximum concentration (tmax) in the PK subset [ Time Frame: 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

  23. Part B: Area under the concentration versus time curve from the beginning to a point in time (AUC0-t) in the PK subset [ Time Frame: 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

  24. Part B: Area under the concentration versus time curve extrapolated to infinity (AUC∞) in the PK subset [ Time Frame: 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

  25. Part B: Terminal rate constant (λz) in the PK subset [ Time Frame: 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

  26. Part B: Apparent terminal half-life (t½) in the PK subset [ Time Frame: 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

  27. Part B: Mean residence time (MRT) in the PK subset [ Time Frame: 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

  28. Part B: Apparent clearance (CL/F) of Debio 1143 in the PK subset [ Time Frame: up to 18 weeks ]
    Categories: alone and in combination with chemotherapy

  29. Part B: Apparent volume of distribution during the terminal phase (Vz/F) of Debio 1143 in the PK subset [ Time Frame: up to 18 weeks ]
    Categories: alone and in combination with chemotherapy

  30. Part B: Total amount of Debio 1143 excreted in urine (Ae) in the PK subset [ Time Frame: up to 18 weeks ]
    Categories: alone and in combination with chemotherapy

  31. Part B: Total amount of Debio 1143 excreted in urine in the first 8 hours (Ae0-8) in the PK subset [ Time Frame: up to 18 weeks ]
    Categories: alone and in combination with chemotherapy

  32. Part B: Total amount of Debio 1143 excreted in urine between 8 and 24 hours (Ae8-24) in the PK subset [ Time Frame: up to 18 weeks ]
    Categories: alone and in combination with chemotherapy

  33. Part B: Renal clearance calculated as Ae/AUC∞ (CLR) of Debio 1143 in the PK subset [ Time Frame: up to 18 weeks ]
    Categories: alone and in combination with chemotherapy

  34. Part B: Fraction of the dose excreted in urine calculated as Ae/dose (fe) of Debio 1143 in the PK subset [ Time Frame: up to 18 weeks ]
    Categories: alone and in combination with chemotherapy

  35. Part B: Area under the concentration versus time curve in the first 12 hours (AUC0-12) in the PK subset [ Time Frame: 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

  36. Part B: Total body clearance (CL) in the PK subset [ Time Frame: 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

  37. Part B: Volume of distribution at steady-state (Vss) in the PK subset [ Time Frame: 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

  38. Part B: Mean Residence Area under the concentration versus time curve (MR,AUC) in the PK subset [ Time Frame: 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

  39. Part B: Mean Residence Maximum Concentration (MR,Cmax) in the PK subset [ Time Frame: 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

  40. Part B: Platinum Refraction (PtR) in ovarian cancer participants included in the PK subset [ Time Frame: 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

  41. Part B: Cmax in patients other than the PK subset [ Time Frame: 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

  42. Part B: Concentration observed at time n (Cn) following Debio 1143 administration in patients other than the PK subset [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01930292


Locations
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France
Centre Georges François Leclerc
Dijon, France, 21079
Centre Léon Bérard
Lyon, France, 69008
Institut Curie
Paris, France, 75248
Institut Claudius Regaud
Toulouse, France, 31052
Sponsors and Collaborators
Debiopharm International SA
Investigators
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Study Chair: Jean-Pierre Delord, MD Institut Claudius Regaud, Toulouse, France

Additional Information:
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Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT01930292     History of Changes
Other Study ID Numbers: Debio 1143-103
2012-003676-40 ( EudraCT Number )
First Posted: August 28, 2013    Key Record Dates
Last Update Posted: March 24, 2016
Last Verified: March 2016
Additional relevant MeSH terms:
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Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action