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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
BIBF 1120 twice daily along with standard therapy of PLD + CBDCA
BIBF 1120 twice daily along with standard therapy of PLD + CBDCA
BIBF 1120 twice daily along with standard therapy of PLD + CBDCA
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
Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) of Nintedanib
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.
Time frame: 28 days
Maximum Measured Plasma Concentration (Cmax)
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
Time frame: 0.5h after the start of the infusion up to 56 days
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz)
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
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Time frame: 0.5h after the start of the infusion up to 56 days
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-∞)
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 frame: 0.5h after the start of the infusion up to 56 days
Time From Dosing to the Maximum Plasma Concentration (Tmax)
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
Time frame: 0.5h after the start of the infusion up to 56 days
Terminal Half-life (t1/2)
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
Time frame: 0.5h after the start of the infusion up to 56 days
Total Plasma Clearance (CL)
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
Time frame: 0.5h after the start of the infusion up to 56 days
Apparent Volume of Distribution at Steady State (Vss)
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
Time frame: 0.5h after the start of the infusion up to 56 days