Trial Outcomes & Findings for Dose Escalation Study of BIBF 1120 in Combination With Carboplatin and PLD in Relapsed Ovarian Cancer (OC) (NCT NCT01329549)

NCT ID: NCT01329549

Last Updated: 2014-11-27

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

2 participants

Primary outcome timeframe

28 days

Results posted on

2014-11-27

Participant Flow

Participant milestones

Participant milestones
Measure
Nintedanib (150 mg) + Carboplatin + PLD
Nintedanib (150 mg) was administered orally on day 2 to Day 28 of each cycle + Carboplatin (AUC 5 mg/mL\*min) intravenous infusion, day 1, once every 4 weeks + Pegylated liposomal doxorubicin (30 mg/m2) intravenous infusion, day 1, once every 4 weeks
Overall Study
STARTED
2
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Nintedanib (150 mg) + Carboplatin + PLD
Nintedanib (150 mg) was administered orally on day 2 to Day 28 of each cycle + Carboplatin (AUC 5 mg/mL\*min) intravenous infusion, day 1, once every 4 weeks + Pegylated liposomal doxorubicin (30 mg/m2) intravenous infusion, day 1, once every 4 weeks
Overall Study
Withdrawal by Subject
1
Overall Study
Adverse Event
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Nintedanib (150 mg) + Carboplatin + PLD
n=2 Participants
Nintedanib (150 mg) was administered orally on day 2 to Day 28 of each cycle + Carboplatin (AUC 5 mg/mL\*min) intravenous infusion, day 1, once every 4 weeks + Pegylated liposomal doxorubicin (30 mg/m2) intravenous infusion, day 1, once every 4 weeks
Age, Continuous
63 years
STANDARD_DEVIATION 1.4 • n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Treated set

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0.5h after the start of the infusion up to 56 days

Population: Treated set

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0.5h after the start of the infusion up to 56 days

Population: Treated set

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0.5h after the start of the infusion up to 56 days

Population: Treated set

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0.5h after the start of the infusion up to 56 days

Population: Treated set

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0.5h after the start of the infusion up to 56 days

Population: Treated set

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0.5h after the start of the infusion up to 56 days

Population: Treated set

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0.5h after the start of the infusion up to 56 days

Population: Treated set

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

Outcome measures

Outcome data not reported

Adverse Events

Nintedanib (150 mg) + Carboplatin + PLD

Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Nintedanib (150 mg) + Carboplatin + PLD
n=2 participants at risk
Nintedanib (150 mg) was administered orally on day 2 to Day 28 of each cycle + Carboplatin (AUC 5 mg/mL\*min) intravenous infusion, day 1, once every 4 weeks + Pegylated liposomal doxorubicin (30 mg/m2) intravenous infusion, day 1, once every 4 weeks
Blood and lymphatic system disorders
Febrile neutropenia
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Injury, poisoning and procedural complications
Fracture
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.

Other adverse events

Other adverse events
Measure
Nintedanib (150 mg) + Carboplatin + PLD
n=2 participants at risk
Nintedanib (150 mg) was administered orally on day 2 to Day 28 of each cycle + Carboplatin (AUC 5 mg/mL\*min) intravenous infusion, day 1, once every 4 weeks + Pegylated liposomal doxorubicin (30 mg/m2) intravenous infusion, day 1, once every 4 weeks
Blood and lymphatic system disorders
Anaemia
100.0%
2/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Blood and lymphatic system disorders
Lymphopenia
100.0%
2/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Metabolism and nutrition disorders
Decreased appetite
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Metabolism and nutrition disorders
Hypokalaemia
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Metabolism and nutrition disorders
Hyponatraemia
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Nervous system disorders
Headache
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Gastrointestinal disorders
Diarrhoea
100.0%
2/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Gastrointestinal disorders
Nausea
100.0%
2/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Gastrointestinal disorders
Cheilitis
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Gastrointestinal disorders
Constipation
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Gastrointestinal disorders
Dyspepsia
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Gastrointestinal disorders
Gingival pain
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Gastrointestinal disorders
Stomatitis
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Gastrointestinal disorders
Vomiting
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Skin and subcutaneous tissue disorders
Alopecia
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Skin and subcutaneous tissue disorders
Rash
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Musculoskeletal and connective tissue disorders
Pain in extremity
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
General disorders
Fatigue
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
General disorders
Pyrexia
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Investigations
Neutrophil count decreased
100.0%
2/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Investigations
Platelet count decreased
100.0%
2/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Investigations
White blood cell count decreased
100.0%
2/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Investigations
Alanine aminotransferase increased
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Investigations
Aspartate aminotransferase increased
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Investigations
Blood alkaline phosphatase increased
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Investigations
Weight decreased
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Investigations
Weight increased
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Injury, poisoning and procedural complications
Fall
100.0%
2/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.
Injury, poisoning and procedural complications
Fracture
50.0%
1/2 • From first administration of study treatment up to 33 days after the last administration of the study treatment, up to 360 days.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Results disclosure agreements

  • Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
  • Publication restrictions are in place

Restriction type: OTHER