Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Digestive System Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Peritoneal Neoplasms

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Doxorubicin

Liposomal doxorubicin

Nintedanib

Protein Kinase Inhibitors

Enzyme Inhibitors

BIBF 1120 (100 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) + PLD (30 mg/m2)

BIBF 1120 (150 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) + PLD (30 mg/m2)

BIBF 1120 (200 mg twice daily (BID)) + Carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) + PLD (30 mg/m2)

BIBF1120 twice daily along with standard therapy of PLD + carboplatin

BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min

BIBF 1120+ PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min

Boehringer Ingelheim

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.

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

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

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.

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

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 during course 1 and course 2.

Maximum measured plasma concentration (Cmax) of nintedanib during course 1 and course 2

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).

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 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).

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).

Maximum measured plasma concentration (Cmax) 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).

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.

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.

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 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 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.

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.

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.

Nintedanib (150 mg twice daily (BID), except the day of chemotherapy infusion) administered orally plus standard therapy of carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) and PLD (30 mg/m2) which were administered by intravenous infusion once every 28 days.

Nintedanib 150mg

Nintedanib (200 mg twice daily (BID), except the day of chemotherapy infusion) administered orally plus standard therapy of carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) and PLD (30 mg/m2) which were administered by intravenous infusion once every 28 days.

Nintedanib 200mg

Total

Age, Continuous

Sex: Female, Male

Treated set (TS) which included all patients who were administered at least one dose of any study medication

Due to interference from doxorubicin, doxorubicinol concentrations could not be determined and doxorubicinol PK parameters could not be evaluated.

Statistics of PK parameters are only estimated when at least 2/3 of the data are evaluable.

Boehringer Ingelheim Call Center

MTD set which included patients in the dose escalation part of the trial who started treatment course 2 and/or took 1 dose of carboplatin and PLD, started nintedanib (nin) and did not miss more than 13 doses of nin and/or took 1 dose of carboplatin and PLD, started nin and discontinued treatment due to a dose limiting toxicity during the MTD period

Maximum Tolerated Dose of Nintedanib Based on the Occurrence of DLTs During Treatment Course 1

Dose Limiting Toxicities During Treatment Course 1

Treatment Course 1 (150mg: N=5; 200mg: N=10)

Treatment Course 2 (150mg: N=7)

Pharmacokinetic (PK) set: All patients in the treated set who were documented to have received at least one dose of nintedanib and who had at least one valid pharmacokinetic parameter concentration available

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Nintedanib

Treatment Course 1 (150mg: N=6; 200mg: N=11)

Treatment Course 2 (150mg: N=8; 200mg: N=7)

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Nintedanib

Maximum Measured Plasma Concentration (Cmax) of Nintedanib

Treatment Course 1 (200mg:N=10; All Patients:N=16)

Treatment Course 2 (200mg:N=7; All Patients:N=16)

Nintedanib (200 mg or 150 mg twice daily (BID), except the day of chemotherapy infusion) administered orally plus standard therapy of carboplatin (Area Under the Curve (AUC) 5 mg/mL\*min) and PLD (30 mg/m2) which were administered by intravenous infusion once every 28 days.

All Patients

PK set.Goal is to find MTD for nintedanib,two doses of nintedanib separately displayed.However carboplatin,PLD are given as background,therefore only measured to know exposure.As result displaying all subjects is sufficient.Further we decided to make separate table for MTD dose(200mg nintedanib).Separate table for 150mg nintedanib doesnt add value.

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carboplatin (Determined as Total Platinum)

Treatment Course 1 (200mg:N=9; All Patients:N=16)

Treatment Course 2 (200mg:N=NA; All Patients:N=NA)

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)

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)

Treatment Course 2 (200mg:N=6; All Patients:N=15)

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)

Maximum Measured Plasma Concentration (Cmax) of Carboplatin (Total Platinum)

Maximum Measured Plasma Concentration (Cmax) of Carboplatin During Course 1 and Course 2 (Determined as Ultrafilterable Platinum)

Treatment Course 1 (200mg:N=NA; All Patients:N=8)

Treatment Course 2 (200mg:N=3; All Patients:N=10)

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

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

Treatment Course 2 (200mg:N=3; All Patients:N=8)

Maximum Measured Plasma Concentration (Cmax) of PLD (Determined as Total Plasma Doxorubicin) 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 PLD (Determined as Plasma Doxorubicinol)

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)

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

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