Dose Escalation Study of BIBF 1120 in Combination With Carboplatin and PLD in Relapsed Ovarian Cancer (OC)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01329549
First received: April 1, 2011
Last updated: November 26, 2014
Last verified: November 2014

April 1, 2011
November 26, 2014
April 2011
October 2012   (final data collection date for primary outcome measure)
Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) of Nintedanib [ Time Frame: 28 days ] [ Designated as safety issue: No ]
to determine the MTD of nintedanib in combination with carboplatin (AUC 5 mg/mL·min) and PLD (30 mg/m2) reflected by the number of DLTs per dose level. This endpoint has not been statistically analyzed in the study report.
To determine Maximum tolerated dose of BIBF 1120 in combination with carboplatin and PLD based on number of Dose Limiting Toxicity (DLT) at each dose level [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01329549 on ClinicalTrials.gov Archive Site
  • Maximum Measured Plasma Concentration (Cmax) [ Time Frame: 0.5h after the start of the infusion up to 56 days ] [ Designated as safety issue: No ]

    Cmax was evaluated for nintedanib (BIBF 1120 BS, BIBF 1202 ZW, BIBF 1202 glucuronide), PLD (doxorubicin), and carboplatin (free platinum, total platinum). This endpoint has not been statistically analyzed in the study report.

    Detailed outcome measure time frame:

    total platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31, 46.917,166.917, 334.917, and 502.917 hours after start of infusion of carboplatin in Cycle 1 and 2

    free platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31 hours after start of infusion of carboplatin in Cycle 1 and 2

    PLD: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.75, 3.25, 4.5, 6.5, 8, 9.5, 25, 27, 30, 34, 47.917, 167.917, 335.917, and 503.917 hours after start of infusion of PLD in Cycle 1 and 2

    nintedanib and its metabolites: pre-dose, 1, 2, 3, 4, 6, 8, 10, 23.917 hours after first administration of nintedanib in Cycle 1 and 2

  • Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) [ Time Frame: 0.5h after the start of the infusion up to 56 days ] [ Designated as safety issue: No ]

    AUC0-tz was evaluated for nintedanib (BIBF 1120 BS, BIBF 1202 ZW, BIBF 1202 glucuronide), PLD (doxorubicin), and carboplatin (free platinum, total platinum). Descriptive statistics were not calculated in the study report.

    Detailed outcome measure time frame:

    total platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31, 46.917,166.917, 334.917, and 502.917 hours after start of infusion of carboplatin in Cycle 1 and 2

    free platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31 hours after start of infusion of carboplatin in Cycle 1 and 2

    PLD: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.75, 3.25, 4.5, 6.5, 8, 9.5, 25, 27, 30, 34, 47.917, 167.917, 335.917, and 503.917 hours after start of infusion of PLD in Cycle 1 and 2

    nintedanib and its metabolites: pre-dose, 1, 2, 3, 4, 6, 8, 10, 23.917 hours after first administration of nintedanib in Cycle 1 and 2

  • Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-∞) [ Time Frame: 0.5h after the start of the infusion up to 56 days ] [ Designated as safety issue: No ]

    AUC0-∞ was evaluated for nintedanib (BIBF 1120 BS, BIBF 1202 ZW), PLD (doxorubicin), and carboplatin (free platinum, total platinum). Descriptive statistics were not calculated in the study report.

    Detailed outcome measure time frame

    total platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31, 46.917,166.917, 334.917, and 502.917 hours after start of infusion of carboplatin in Cycle 1 and 2

    free platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31 hours after start of infusion of carboplatin in Cycle 1 and 2

    PLD: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.75, 3.25, 4.5, 6.5, 8, 9.5, 25, 27, 30, 34, 47.917, 167.917, 335.917, and 503.917 hours after start of infusion of PLD in Cycle 1 and 2

    nintedanib and its metabolites: pre-dose, 1, 2, 3, 4, 6, 8, 10, 23.917 hours after first administration of nintedanib in Cycle 1 and 2

  • Time From Dosing to the Maximum Plasma Concentration (Tmax) [ Time Frame: 0.5h after the start of the infusion up to 56 days ] [ Designated as safety issue: No ]

    tmax was evaluated for nintedanib (BIBF 1120 BS, BIBF 1202 ZW, BIBF 1202 glucuronide), PLD (doxorubicin), and carboplatin (free platinum, total platinum). Descriptive statistics were not calculated in the study report.

    Detailed outcome measure time frame:

    total platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31, 46.917,166.917, 334.917, and 502.917 hours after start of infusion of carboplatin in Cycle 1 and 2

    free platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31 hours after start of infusion of carboplatin in Cycle 1 and 2

    PLD: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.75, 3.25, 4.5, 6.5, 8, 9.5, 25, 27, 30, 34, 47.917, 167.917, 335.917, and 503.917 hours after start of infusion of PLD in Cycle 1 and 2

    nintedanib and its metabolites: pre-dose, 1, 2, 3, 4, 6, 8, 10, 23.917 hours after first administration of nintedanib in Cycle 1 and 2

  • Terminal Half-life (t1/2) [ Time Frame: 0.5h after the start of the infusion up to 56 days ] [ Designated as safety issue: No ]

    t1/2 was evaluated for nintedanib (BIBF 1120 BS, BIBF 1202 ZW), PLD (doxorubicin), and carboplatin (free platinum, total platinum). Descriptive statistics were not calculated in the study report.

    Detailed outcome measure time frame:

    total platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31, 46.917,166.917, 334.917, and 502.917 hours after start of infusion of carboplatin in Cycle 1 and 2

    free platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31 hours after start of infusion of carboplatin in Cycle 1 and 2

    PLD: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.75, 3.25, 4.5, 6.5, 8, 9.5, 25, 27, 30, 34, 47.917, 167.917, 335.917, and 503.917 hours after start of infusion of PLD in Cycle 1 and 2

    nintedanib and its metabolites: pre-dose, 1, 2, 3, 4, 6, 8, 10, 23.917 hours after first administration of nintedanib in Cycle 1 and 2

  • Total Plasma Clearance (CL) [ Time Frame: 0.5h after the start of the infusion up to 56 days ] [ Designated as safety issue: No ]

    CL was evaluated for doxorubicin, free platinum, total platinum. Descriptive statistics were not calculated in the study report.

    Detailed outcome measure time frame:

    total platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31, 46.917,166.917, 334.917, and 502.917 hours after start of infusion of carboplatin in Cycle 1 and 2

    free platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31 hours after start of infusion of carboplatin in Cycle 1 and 2

    PLD: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.75, 3.25, 4.5, 6.5, 8, 9.5, 25, 27, 30, 34, 47.917, 167.917, 335.917, and 503.917 hours after start of infusion of PLD in Cycle 1 and 2

  • Apparent Volume of Distribution at Steady State (Vss) [ Time Frame: 0.5h after the start of the infusion up to 56 days ] [ Designated as safety issue: No ]

    Vss was evaluated for doxorubicin, free platinum, total platinum. Descriptive statistics were not calculated in the study report.

    total platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31, 46.917,166.917, 334.917, and 502.917 hours after start of infusion of carboplatin in Cycle 1 and 2

    free platinum: pre-dose, 0.5, 1, 1.25, 1.75, 2.25, 3.5, 5.5, 7, 8.5, 22.917, 25, 27, 31 hours after start of infusion of carboplatin in Cycle 1 and 2

    PLD: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.75, 3.25, 4.5, 6.5, 8, 9.5, 25, 27, 30, 34, 47.917, 167.917, 335.917, and 503.917 hours after start of infusion of PLD in Cycle 1 and 2

  • Frequency and intensity of adverse events graded by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and changes in safety laboratory parameters [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Potential pharmacokinetic (PK) drug-drug interaction between BIBF 1120 and a combined administration of PLD and carboplatin [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Time to tumour progression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Objective tumour response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Duration of objective tumour response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Serological progression-free interval (based on CA-125 mesurements) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Dose Escalation Study of BIBF 1120 in Combination With Carboplatin and PLD in Relapsed Ovarian Cancer (OC)
An Open-label, Dose Escalation Phase I Study of the Safety and Tolerability of BIBF 1120 in Combination With Carboplatin and Pegylated Liposomal Doxorubicin (PLD) in Japanese Patients With a First, Second or Third Platinum-sensitive Relapse of Advanced Epithelial Ovarian Cancer, Fallopian Tube or Primary Peritoneal Cancer.
This phase I, open label dose escalation study will investigate the addition of BIBF 1120 to treatment with the combination of carboplatin and Pegylated Liposomal Doxorubicin (PLD) in patients with advanced, platinum sensitive relapsed ovarian cancer, fallopian tube carcinoma or primary peritoneal cancer. Patients will be treated with BIBF 1120 together with carboplatin and PLD in up to 6-9 repeated 28 days treatment courses until disease progression is observed.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Ovarian Neoplasms
  • Drug: BIBF 1120 (high) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
    BIBF 1120 twice daily along with standard therapy of PLD + CBDCA
  • Drug: BIBF 1120 (medium) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
    BIBF 1120 twice daily along with standard therapy of PLD + CBDCA
  • Drug: BIBF 1120 (low) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
    BIBF 1120 twice daily along with standard therapy of PLD + CBDCA
  • Experimental: BIBF 1120 (low) + Carboplatin + PLD
    BIBF 1120 (low dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
    Intervention: Drug: BIBF 1120 (low) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
  • Experimental: BIBF 1120 (medium) + Carboplatin + PLD
    BIBF 1120 (medium dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
    Intervention: Drug: BIBF 1120 (medium) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
  • Experimental: BIBF 1120 (high) + Carboplatin + PLD
    BIBF 1120 (high dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
    Intervention: Drug: BIBF 1120 (high) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
2
October 2012
October 2012   (final data collection date for primary outcome measure)

Inclusion criteria:

  1. Female patients, age 20 years or older, with relapse of histologically (on initial diagnosis) confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal cancer
  2. Up to 3 lines of prior chemo therapy, with treatment free interval of >6 months
  3. Platinum based chemotherapy in the immediately preceding line.
  4. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
  5. Written informed consent that is consistent with Good Clinical Practice (GCP) guidelines

Exclusion criteria:

  1. Prior chemotherapy with PLD, and any contraindication for therapy with carboplatin or PLD.
  2. More than 2 lines of prior therapies that contained angiogenesis inhibitor.
  3. Patients for whom surgery is planned, e.g. interval debulking surgery.
  4. History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.
  5. Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy.
  6. Laboratory values indicating an increased risk for adverse events.
  7. Significant cardiovascular diseases.
Female
20 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT01329549
1199.117
Not Provided
Not Provided
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP