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

Phase 1

Completed

• Conditions: Ovarian Neoplasms; Peritoneal Neoplasms
• Interventions: Drug: BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min; Drug: BIBF 1120+ PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min

• Registration Number: NCT01314105
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-03-08
• Study First Submitted QC: 2011-03-10
• Study First Posted: 2011-03-14
• Primary Completion: 2013-07
• Results First Submitted: 2014-11-14
• Results First Submitted QC: 2014-11-14
• Results First Posted: 2014-11-20
• Study Completion: 2016-04
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-07
• Last Update Posted: 2018-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 19

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BIBF 1120 L+ Carboplatin + PLD	BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min	BIBF 1120 (100 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) + PLD (30 mg/m2)
BIBF 1120 M + Carboplatin + PLD	BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min	BIBF 1120 (150 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) + PLD (30 mg/m2)
BIBF 1120 H + Carboplatin + PLD	BIBF 1120+ PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min	BIBF 1120 (200 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) + PLD (30 mg/m2)

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose of Nintedanib Based on the Occurrence of DLTs During Treatment Course 1	First 28-day treatment cycle	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.
Dose Limiting Toxicities During Treatment Course 1	First 28-day treatment cycle	Number of patients with dose limiting toxicity (DLT) occurring during treatment course 1; The following AEs were to be reported as DLT events if their occurrence was considered to be drug-related: Haematological toxicity: * Any CTCAE grade 4 haematological toxicity; * CTCAE grade 4 neutropenia that was not associated with fever ≥38.5°C, if persisting for \>7 days despite adequate supportive treatment; * CTCAE grade ≥3 neutropenia of any duration if associated with fever ≥38.5°C; * Any CTCAE grade 4 thrombocytopenia; * CTCAE grade ≥3 thrombocytopenia if associated with bleeding of CTCAE grade ≥2; Non-haematological toxicity: * CTCAE grade ≥3 diarrhoea despite optimal medical management; * CTCAE grade 2 diarrhoea persisting for more than 7 days despite optimal medical management; * CTCAE grade ≥2 vomiting despite optimal medical management; * ALT and/or AST elevation of CTCAE grade ≥3; * ALT and/or AST elevation of \>3x ULN in conjunction with bilirubin increase \>2x ULN

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Carboplatin (Determined as Ultrafilterable Platinum)	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, and 34h after drug administration	Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of carboplatin during course 1 and course 2 (determined as ultrafilterable platinum).
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Nintedanib	5 minutes (min) before drug administration and 1 hour (h) 2h, 3h, 4h, 6h, 8h, 10h, 24h, 144h, 312h and 456h after drug administration	Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of nintedanib during course 1 and course 2
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Nintedanib	5 minutes (min) before drug administration and 1 hour (h) 2h, 3h, 4h, 6h, 8h, 10h, 24h, 144h, 312h and 456h after drug administration	Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of nintedanib during course 1 and course 2.
Maximum Measured Plasma Concentration (Cmax) of Nintedanib	5 minutes (min) before drug administration and 1 hour (h) 2h, 3h, 4h, 6h, 8h, 10h, 24h, 144h, 312h and 456h after drug administration	Maximum measured plasma concentration (Cmax) of nintedanib during course 1 and course 2
Maximum Measured Plasma Concentration (Cmax) of Carboplatin (Total Platinum)	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, 26h, 28h, 32h, 48h, 168h, 336h and 480h after drug administration	Maximum measured plasma concentration (Cmax) of carboplatin during course 1 and course 2 (determined as total platinum).
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Carboplatin (Determined as Total Platinum)	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, 26h, 28h, 32h, 48h, 168h, 336h and 480h after drug administration	Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of carboplatin during course 1 and course 2 (determined as total platinum).
Maximum Measured Plasma Concentration (Cmax) of Carboplatin During Course 1 and Course 2 (Determined as Ultrafilterable Platinum)	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, and 34h after drug administration	Maximum measured plasma concentration (Cmax) of carboplatin during course 1 and course 2 (determined as ultrafilterable platinum).
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carboplatin (Determined as Total Platinum)	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, 26h, 28h, 32h, 48h, 168h, 336h and 480h after drug administration	Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of carboplatin (determined as total platinum) during treatment course 1 and course 2.
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC 0-inf) of Carboplatin During Treatment Course 1 and Course 2 (Determined as Ultrafilterable Platinum)	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, and 34h after drug administration	Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC 0-inf) of carboplatin during treatment course 1 and course 2 (determined as ultrafilterable platinum).; Geometric mean (gMean) and Geometric coefficient of Variation (gCV) were not calculable for treatment course 2 as 2/3 of patients had quantifiable values.
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC 0-inf) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2	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	Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC 0-inf) of pegylated liposomal doxorubicin (PLD) (determined as total plasma doxorubicin) during treatment course 1 and course 2.; Geometric mean (gMean) and Geometric coefficient of Variation (gCV) were not calculable for treatment course 1 as for only 2 patients evaluable concentrations were available.
Maximum Measured Plasma Concentration (Cmax) of PLD (Determined as Plasma Doxorubicinol)	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	The maximum measured plasma concentration (Cmax) of pegylated liposomal doxorubicin (PLD) (determined as plasma doxorubicinol).; Due to interference from doxorubicin, doxorubicinol concentrations could not be determined and doxorubicinol PK parameters could not be evaluated.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2	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	Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of pegylated liposomal doxorubicin (PLD) (determined as total plasma doxorubicin) during treatment course 1 and course 2.; Geometric mean (gMean) and Geometric coefficient of Variation (gCV) were not calculable for treatment course 1 as for only 2 patients evaluable concentrations were available.
Maximum Measured Plasma Concentration (Cmax) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2	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	The maximum measured plasma concentration (Cmax) of pegylated liposomal doxorubicin (PLD) (determined as total plasma doxorubicin) during treatment course 1 and course 2.; Geometric mean (gMean) and Geometric coefficient of Variation (gCV) were not calculable for treatment course 1 as for only 2 patients evaluable concentrations were available.
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC 0-inf) of PLD (Determined as Plasma Doxorubicinol)	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	Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC 0-inf) of pegylated liposomal doxorubicin (PLD) (determined as plasma doxorubicinol).; Due to interference from doxorubicin, doxorubicinol concentrations could not be determined and doxorubicinol PK parameters could not be evaluated.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of PLD (Determined as Plasma Doxorubicinol)	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	Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of pegylated liposomal doxorubicin (PLD) (determined as plasma doxorubicinol).; Due to interference from doxorubicin, doxorubicinol concentrations could not be determined and doxorubicinol PK parameters could not be evaluated.
Incidence and Intensity of Adverse Events	From the first drug administration until 28 days after the last drug administration, up to 31 months	Safety of nintedanib as indicated by intensity and incidence of adverse events, graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.; The CTCAE grades are the worst grade per patient. The CTCAE grades are Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as lifethreatening or disabling AE, and Grade 5 as death related to AE.
Change From Baseline in Safety Laboratory Parameters	From the first drug administration until 28 days after the last drug administration, up to 31 months	Change from baseline in safety laboratory parameters.

Trial Locations

Locations (3)

1199.119.34002 Boehringer Ingelheim Investigational Site; 🇪🇸 Barcelona, Spain

1199.119.34001 Boehringer Ingelheim Investigational Site; 🇪🇸 Barcelona, Spain

1199.119.34003 Boehringer Ingelheim Investigational Site; 🇪🇸 L'Hospitalet de Llobregat, Spain