Dose Escalation Study of BIBF 1120 in Combination With Carboplatin and PLD in Relapsed Ovarian Cancer (OC)

Phase 1

Terminated

• Conditions: Ovarian Neoplasms
• Interventions: Drug: BIBF 1120 (medium) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min; Drug: BIBF 1120 (high) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min; Drug: BIBF 1120 (low) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min

• Registration Number: NCT01329549
• 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. 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2011-04-01
• Study First Submitted QC: 2011-04-04
• Study First Posted: 2011-04-06
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2014-11
• Results First Submitted: 2014-11-14
• Results First Submitted QC: 2014-11-26
• Last Update Submitted: 2014-11-26
• Results First Posted: 2014-11-27
• Last Update Posted: 2014-11-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 2

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 (medium) + Carboplatin + PLD	BIBF 1120 (medium) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min	BIBF 1120 (medium dose) + carboplatin (AUC5 mg/mL\*min) + PLD (30 mg/m2)
BIBF 1120 (high) + Carboplatin + PLD	BIBF 1120 (high) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min	BIBF 1120 (high dose) + carboplatin (AUC5 mg/mL\*min) + PLD (30 mg/m2)
BIBF 1120 (low) + Carboplatin + PLD	BIBF 1120 (low) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min	BIBF 1120 (low dose) + carboplatin (AUC5 mg/mL\*min) + PLD (30 mg/m2)

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) of Nintedanib	28 days	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

Name	Time	Method
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-∞)	0.5h after the start of the infusion up to 56 days	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
Maximum Measured Plasma Concentration (Cmax)	0.5h after the start of the infusion up to 56 days	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)	0.5h after the start of the infusion up to 56 days	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
Time From Dosing to the Maximum Plasma Concentration (Tmax)	0.5h after the start of the infusion up to 56 days	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)	0.5h after the start of the infusion up to 56 days	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)	0.5h after the start of the infusion up to 56 days	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)	0.5h after the start of the infusion up to 56 days	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

Trial Locations

Locations (3)

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