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
  Purpose

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.


Condition Intervention Phase
Ovarian Neoplasms
Drug: BIBF 1120 (high) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
Drug: BIBF 1120 (medium) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
Drug: BIBF 1120 (low) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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



Enrollment: 2
Study Start Date: April 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBF 1120 (low) + Carboplatin + PLD
BIBF 1120 (low dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
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 (medium) + Carboplatin + PLD
BIBF 1120 (medium dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
Drug: BIBF 1120 (medium) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
BIBF 1120 twice daily along with standard therapy of PLD + CBDCA
Experimental: BIBF 1120 (high) + Carboplatin + PLD
BIBF 1120 (high dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
Drug: BIBF 1120 (high) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
BIBF 1120 twice daily along with standard therapy of PLD + CBDCA

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01329549

Locations
Japan
1199.117.003 Boehringer Ingelheim Investigational Site
Akashi, Hyogo, Japan
1199.117.002 Boehringer Ingelheim Investigational Site
Chuo-ku,Tokyo, Japan
1199.117.001 Boehringer Ingelheim Investigational Site
Hidaka, Saitama, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01329549     History of Changes
Other Study ID Numbers: 1199.117
Study First Received: April 1, 2011
Results First Received: November 14, 2014
Last Updated: November 26, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Carboplatin
Doxorubicin
Liposomal doxorubicin
Nintedanib
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on August 27, 2015