NCT01314105

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

Completed Phase 1 Results posted Last updated 13 February 2025

What this trial tests

Phase 1 trial testing BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min in Ovarian Neoplasms in 19 participants. Completed in 4 April 2016.

Timeline

15 March 2011

Primary endpoint
29 July 2013

4 April 2016

Quick facts

Lead sponsor	Boehringer Ingelheim
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	19
Start date	15 March 2011
Primary completion	29 July 2013
Estimated completion	4 April 2016
Sites	3 locations across Spain

Drugs / interventions tested

• BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min — full drug profile →
• BIBF 1120+ PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
• BIBF 1120 + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min — full drug profile →

Conditions studied

• Ovarian Neoplasms — all drugs for Ovarian Neoplasms →
• Peritoneal Neoplasms — all drugs for Peritoneal Neoplasms →

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, female only, with Ovarian Neoplasms or Peritoneal Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Nintedanib 150mg	NA
Nintedanib 200mg	200

Dose Limiting Toxicities During Treatment Course 1 Primary · 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

Group	Value	95% CI
Nintedanib 150mg	1
Nintedanib 200mg	1

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

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

Group	Value	95% CI
Nintedanib 150mg	335	± 88.5
Nintedanib 200mg	482	± 38.8

Treatment Course 2 (150mg: N=7)

Group	Value	95% CI
Nintedanib 150mg	482	± 76.1
Nintedanib 200mg	NA	± NA

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

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

Group	Value	95% CI
Nintedanib 150mg	283	± 70.2
Nintedanib 200mg	422	± 36.9

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

Group	Value	95% CI
Nintedanib 150mg	406	± 59.0
Nintedanib 200mg	476	± 37.6

Maximum Measured Plasma Concentration (Cmax) of Nintedanib Secondary · 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

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

Group	Value	95% CI
Nintedanib 150mg	38.8	± 40.3
Nintedanib 200mg	69.0	± 27.9

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

Group	Value	95% CI
Nintedanib 150mg	65.8	± 51.6
Nintedanib 200mg	82.2	± 43.0

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

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

Group	Value	95% CI
Nintedanib 200mg	271000	± 15.1
All Patients	267000	± 15.1

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

Group	Value	95% CI
Nintedanib 200mg	325000	± 15.4
All Patients	324000	± 14.7

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) Secondary · 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.

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

Group	Value	95% CI
Nintedanib 200mg	71000	± 69.3
All Patients	70700	± 107

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

Group	Value	95% CI
Nintedanib 200mg	NA	± NA
All Patients	NA	± NA

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) Secondary · 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).

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

Group	Value	95% CI
Nintedanib 200mg	223000	± 18.4
All Patients	220000	± 17.1

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

Group	Value	95% CI
Nintedanib 200mg	258000	± 15.8
All Patients	260000	± 14.7

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) Secondary · 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).

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

Group	Value	95% CI
Nintedanib 200mg	58500	± 26.0
All Patients	53800	± 26.7

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

Group	Value	95% CI
Nintedanib 200mg	56200	± 26.5
All Patients	55700	± 29.8

Maximum Measured Plasma Concentration (Cmax) of Carboplatin (Total Platinum) Secondary · 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).

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

Group	Value	95% CI
Nintedanib 200mg	24600	± 49.1
All Patients	24000	± 37.7

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

Group	Value	95% CI
Nintedanib 200mg	27100	± 22.7
All Patients	23900	± 25.2

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

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

Group	Value	95% CI
Nintedanib 200mg	26000	± 48.4
All Patients	24600	± 38.0

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

Group	Value	95% CI
Nintedanib 200mg	27000	± 26.6
All Patients	24400	± 23.0

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 Secondary · 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.

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

Group	Value	95% CI
Nintedanib 200mg	NA	± NA
All Patients	2280	± 20.1

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

Group	Value	95% CI
Nintedanib 200mg	2120	± 38.4
All Patients	2300	± 25.5

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first drug administration until 28 days after the last drug administration, up to 31months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nintedanib 150mg

Serious: 3/7 (43%)

Deaths: —

Nintedanib 200mg

Serious: 4/12 (33%)

Deaths: —

Serious adverse events (7 terms)

Reaction	System	Nintedanib 150mg	Nintedanib 200mg
Ileus	Gastrointestinal disorders	—	—
Intestinal obstruction	Gastrointestinal disorders	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—
Hypersensitivity	Immune system disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (137 terms — click to expand)

Reaction	System	Nintedanib 150mg	Nintedanib 200mg
Neutropenia	Blood and lymphatic system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Gamma-glutamyltransferase increased	Investigations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Mucosal inflammation	General disorders	—	—
Platelet count decreased	Investigations	—	—
Pyrexia	General disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Headache	Nervous system disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Odynophagia	Gastrointestinal disorders	—	—
Stomatitis	Gastrointestinal disorders	—	—
Blood alkaline phosphatase increased	Investigations	—	—
Dizziness	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Flatulence	Gastrointestinal disorders	—	—
Blood alkaline phosphatase	Investigations	—	—
Blood lactate dehydrogenase increased	Investigations	—	—
Haemoglobin decreased	Investigations	—	—
Neutrophil count decreased	Investigations	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Paraesthesia	Nervous system disorders	—	—
Anxiety	Psychiatric disorders	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—

Most-reported serious reactions: Ileus, Intestinal obstruction, Small intestinal obstruction, Hypersensitivity, Alanine aminotransferase increased, Platelet count decreased, Pulmonary embolism.

Data from ClinicalTrials.gov NCT01314105 adverse events section.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Towards extracellular matrix normalization for improved treatment of solid tumors.
   Abyaneh HS, Regenold M, McKee TD, Allen C, et al · · 2020 · cited 83× · PMID 32042347 · DOI 10.7150/thno.39995
2. Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches.
   Choi HJ, Armaiz Pena GN, Pradeep S, Cho MS, et al · · 2015 · cited 73× · PMID 25544368 · DOI 10.1007/s10555-014-9538-9
3. Understanding and targeting resistance to anti-angiogenic therapies.
   Clarke JM, Hurwitz HI. · · 2013 · cited 69× · PMID 23997938 · DOI 10.3978/j.issn.2078-6891.2013.036
4. Investigational agents in development for the treatment of ovarian cancer.
   Westin SN, Herzog TJ, Coleman RL. · · 2013 · cited 19× · PMID 22661305 · DOI 10.1007/s10637-012-9837-3
5. Fibroblast growth factor receptor signaling as therapeutic targets in female reproductive system cancers.
   Zhu DL, Tuo XM, Rong Y, Zhang K, et al · · 2020 · cited 15× · PMID 33193890 · DOI 10.7150/jca.44727
6. Clinical utility of targeted treatments in the management of epithelial ovarian cancer.
   Twu C, Han ES. · · 2012 · cited 3× · PMID 22904615 · DOI 10.2147/btt.s29356
7. Tyrosine kinase inhibitors (TKIs) for ovarian cancer treatment: from organic to inorganic chemotherapeutics towards selectivity-a perspective overview.
   Baglini E, Chiaverini L, Tolbatov I, Taliani S, et al · · 2024 · cited 2× · PMID 37930483 · DOI 10.1007/s10534-023-00547-0