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

NCT01314105 | Completed Phase 1 Results

• 2 other identifiers: 1199.1192010-022523-30
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

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.

Conditions

Ovarian Neoplasms; Peritoneal Neoplasms

Outcome Measures

Primary Outcomes (2)

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

  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.

  First 28-day treatment cycle

• Dose Limiting Toxicities During Treatment Course 1

  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

  First 28-day treatment cycle

Secondary Outcomes (17)

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

  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

  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

  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 Carboplatin (Determined as Total Platinum)

  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 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)

  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

Study Arms (3)

BIBF 1120 L+ Carboplatin + PLD

EXPERIMENTAL

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

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

BIBF 1120 M + Carboplatin + PLD

EXPERIMENTAL

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

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

BIBF 1120 H + Carboplatin + PLD

EXPERIMENTAL

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

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

Interventions

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

BIBF1120 twice daily along with standard therapy of PLD + carboplatin

BIBF 1120 M + Carboplatin + PLD

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients, age 18 years or older, with a first, second or third relapse of histologically (on initial diagnosis) confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal cancer
• Up to three lines of prior chemo (chemotherapy before and after interval surgery to be counted as one line therapy), with treatment free interval of \> 6 months (= time between last administration of prior anti-cancer treatment, including chemotherapy, hormonal therapy, or radiation therapy, and diagnosis of progressive disease)
• Platinum based chemo in immediately preceding line
• Eligibility for treatment with i.v. chemotherapy regimen of carboplatin AUC 5 and PLD 30 mg/m2 every 4 weeks
• Life expectancy of at least 3 months
• Written informed consent that is consistent with International Conference of Harmonisation (ICH)-Good Clinical Practice (GCP) guidelines
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or1
• Prior treatment with angiogenesis inhibitor (bevacizumab, TKI inhibiting VEGFR-2) is allowed provided treatment with bevacizumab has been discontinued = 28 days prior to start of therapy and treatment with the TKI has been discontinued = 3 months prior to start of therapy, provided anti-angiogenic therapy was added to only one of the preceding lines of therapy

You may not qualify if:

• Prior chemotherapy with doxorubicin (any formulation, liposomal or non-liposomal doxorubicin).
• Any contraindications for therapy with PLD or carboplatin, e.g. a history of hypersensitivity reactions to platinum-containing compounds and their excipients.
• Hypersensitivity to active substance or to any of the excipients of BIBF 1120.
• Laboratory values indicating an increased risk for adverse events.
• Major surgery within 4 weeks prior to start of study treatment.
• Patients for whom surgery is planned, e.g. interval debulking surgery.
• Clinically relevant non-healing wound, ulcer (intestinal tract, skin) or bone fracture.
• Clinical symptoms or signs of gastrointestinal obstruction that require parenteral nutrition or hydration.
• Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug.
• History of clinical symptoms of brain metastases.
• Prior thrombosis or thromboembolic event in the presence of an inherited coagulopathy.
• History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.
• Known inherited or acquired bleeding disorder.
• Significant cardiovascular diseases.
• Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08907, Spain

Location

Related Links

• Related Info

MeSH Terms

Conditions

Ovarian Neoplasms; Peritoneal Neoplasms

Interventions

nintedanib; 1-dodecylpyridoxal

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2011
• First Posted: March 14, 2011
• Study Start: March 15, 2011
• Primary Completion: July 29, 2013
• Study Completion: April 4, 2016
• Last Updated: February 13, 2025
• Results First Posted: November 20, 2014

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3)