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BIBF 1120 + Carboplatin/Pegylated Liposomal Doxorubicin (PLD) in Patients With Advanced Ovarian Cancer, Fallopian Tube Carcinoma or Primary Peritoneal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01314105
First received: March 8, 2011
Last updated: November 14, 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.


Condition Intervention Phase
Ovarian Neoplasms
Peritoneal Neoplasms
Drug: BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
Drug: BIBF 1120+ 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: Phase I Dose Escalation Trial to Determine the Maximum Tolerated Dose of BIBF 1120 in Combination With Carboplatin and Pegylated Liposomal Doxorubicin (PLD) in 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:
  • Maximum Tolerated Dose of Nintedanib Based on the Occurrence of DLTs During Treatment Course 1 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Maximum Tolerated Dose (MTD) of Nintedanib in combination with carboplatin and pegylated liposomal doxorubicin based on the occurrence of dose limiting toxicities (DLTs) during treatment course 1. MTD will be determined among the first 6 evaluable patients in each dose level. MTD is the highest dose at which the incidence of DLT is less than 2/6.


Secondary Outcome Measures:
  • Area Under the Curve of PLD [ Time Frame: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 25h, 27h, 30h, 34h, 48h, 168h, 336h and 480h after drug administration ] [ Designated as safety issue: No ]

    Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC 0-inf) and area under the plasma concentration-time curve over the time interval from zero to the time of the last quantifiable drug concentration (AUC0-tz) of pegylated liposomal doxorubicin (PLD) (total plasma doxorubicin and doxorubicinol)

    As the study is still ongoing, this endpoint has not yet been analysed.


  • The Maximum Measured Plasma Concentration of PLD [ Time Frame: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 25h, 27h, 30h, 34h, 48h, 168h, 336h and 480h after drug administration ] [ Designated as safety issue: No ]

    The maximum measured plasma concentration (Cmax) of pegylated liposomal doxorubicin (PLD) (Total Plasma Doxorubicin and Doxorubicinol)

    As the study is still ongoing, this endpoint has not yet been analysed.


  • Area Under the Curve of Carboplatin [ Time Frame: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 23h 55min, 25h, 26h, 27h, 28h, 30h, 32h, 34h, 48h, 168h, 336h and 480h after drug administration ] [ Designated as safety issue: No ]

    Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC 0-inf) and area under the plasma concentration-time curve over the time interval from zero to the time of the last quantifiable drug concentration (AUC0-tz) of Carboplatin (determined as ultrafiltrable and total platinum)

    As the study is still ongoing, this endpoint has not yet been analysed.


  • The Maximum Measured Plasma Concentration of Carboplatin [ Time Frame: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 23h 55min, 25h, 26h, 27h, 28h, 30h, 32h, 34h, 48h, 168h, 336h and 480h after drug administration ] [ Designated as safety issue: No ]

    The maximum measured plasma concentration of carboplatin (determined as ultrafiltrable and total platinum)

    As the study is still ongoing, this endpoint has not yet been analysed.


  • Area Under the Curve of Nintedanib [ Time Frame: 5 minutes (min) before drug administration and 1 hour (h) 2h, 3h, 4h, 6h, 8h, 10h, 24h, 144h, 312h and 456h after drug administration ] [ Designated as safety issue: No ]

    Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC 0-inf) and area under the plasma concentration-time curve over the time interval from zero to the time of the last quantifiable drug concentration (AUC0-tz) of nintedanib

    As the study is still ongoing, this endpoint has not yet been analysed.


  • The Maximum Measured Plasma Concentration of Nintedanib [ Time Frame: 5 minutes (min) before drug administration and 1 hour (h) 2h, 3h, 4h, 6h, 8h, 10h, 24h, 144h, 312h and 456h after drug administration ] [ Designated as safety issue: No ]

    The maximum measured plasma concentration (Cmax) of nintedanib.

    As the study is still ongoing, this endpoint has not yet been analysed.


  • Frequency of All Adverse Events Graded by CTCAE (Common Terminology Criteria for Adverse Events) Version 3.0 [ Time Frame: From the first drug administration until 28 days after the last drug administration, up to 50 months ] [ Designated as safety issue: No ]

    Frequency of all adverse events graded by CTCAE (Common Terminology Criteria for Adverse Events) version 3.0.

    As the study is still ongoing, this endpoint has not yet been analysed.


  • Change From Baseline in Safety Laboratory Parameters [ Time Frame: From the first drug administration until 28 days after the last drug administration, up to 50 months ] [ Designated as safety issue: No ]

    Change from baseline in safety laboratory parameters.

    As the study is still ongoing, this endpoint has not yet been analysed.



Enrollment: 19
Study Start Date: March 2011
Estimated Study Completion Date: May 2015
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBF 1120 L+ Carboplatin + PLD
BIBF 1120 (100 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL*min) + PLD (30 mg/m2)
Drug: BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
BIBF1120 twice daily along with standard therapy of PLD + carboplatin
Experimental: BIBF 1120 M + Carboplatin + PLD
BIBF 1120 (150 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL*min) + PLD (30 mg/m2)
Drug: BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
BIBF1120 twice daily along with standard therapy of PLD + carboplatin
Experimental: BIBF 1120 H + Carboplatin + PLD
BIBF 1120 (200 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL*min) + PLD (30 mg/m2)
Drug: BIBF 1120+ PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
BIBF1120 twice daily along with standard therapy of PLD + carboplatin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Female patients, age 18 years or older, with a first, second or third relapse of histologically (on initial diagnosis) confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal cancer
  2. Up to three lines of prior chemo (chemotherapy before and after interval surgery to be counted as one line therapy), with treatment free interval of > 6 months (= time between last administration of prior anti-cancer treatment, including chemotherapy, hormonal therapy, or radiation therapy, and diagnosis of progressive disease)
  3. Platinum based chemo in immediately preceding line
  4. Eligibility for treatment with i.v. chemotherapy regimen of carboplatin AUC 5 and PLD 30 mg/m2 every 4 weeks
  5. Life expectancy of at least 3 months
  6. Written informed consent that is consistent with International Conference of Harmonisation (ICH)-Good Clinical Practice (GCP) guidelines
  7. Eastern Cooperative Oncology Group (ECOG) performance score 0 or1
  8. Prior treatment with angiogenesis inhibitor (bevacizumab, TKI inhibiting VEGFR-2) is allowed provided treatment with bevacizumab has been discontinued = 28 days prior to start of therapy and treatment with the TKI has been discontinued = 3 months prior to start of therapy, provided anti-angiogenic therapy was added to only one of the preceding lines of therapy

Exclusion criteria:

  1. Prior chemotherapy with doxorubicin (any formulation, liposomal or non-liposomal doxorubicin).
  2. Any contraindications for therapy with PLD or carboplatin, e.g. a history of hypersensitivity reactions to platinum-containing compounds and their excipients.
  3. Hypersensitivity to active substance or to any of the excipients of BIBF 1120.
  4. Treatment with other investigational drugs or participation in another clinical trial testing a drug within the past four weeks before start of therapy or concomitantly with this trial (exception: for previous treatment with angiogenesis inhibitors, cf. inclusion criterion #8).
  5. Laboratory values indicating an increased risk for adverse events.
  6. Major surgery within 4 weeks prior to start of study treatment.
  7. Patients for whom surgery is planned, e.g. interval debulking surgery.
  8. Clinically relevant non-healing wound, ulcer (intestinal tract, skin) or bone fracture.
  9. Clinical symptoms or signs of gastrointestinal obstruction that require parenteral nutrition or hydration.
  10. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug.
  11. History of clinical symptoms of brain metastases.
  12. Prior thrombosis or thromboembolic event in the presence of an inherited coagulopathy.
  13. History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.
  14. Known inherited or acquired bleeding disorder.
  15. Significant cardiovascular diseases.
  16. Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy.
  17. Other malignancy diagnosed within the past 5 years.
  18. Known serious illness or concomitant non-oncological disease.
  19. Patients unable to comply with the protocol.
  20. Patients with preserved reproductive capacity who are sexually active and unwilling to use a medically acceptable method of contraception.
  21. Pregnancy or breast feeding.
  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: NCT01314105

Locations
Spain
1199.119.34001 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1199.119.34002 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1199.119.34003 Boehringer Ingelheim Investigational Site
L'Hospitalet de Llobregat, Spain
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: NCT01314105     History of Changes
Other Study ID Numbers: 1199.119, 2010-022523-30
Study First Received: March 8, 2011
Results First Received: November 14, 2014
Last Updated: November 14, 2014
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms by Site
Ovarian Diseases
Peritoneal 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 November 24, 2014