Phase I/II Comparison of Efficacy and Safety of BIBF 1120 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

NCT01004003 | Completed Phase 2 Results

• 2 other identifiers: 1199.372009-011925-14
• Study Type: interventional
• Target: 125
• Locations: 8 countries
• Sites: 28

Brief Summary

The study aim is to determine maximally tolerated dose (MTD) of BIBF 1120 in HCC (hepatocellular cancer) and compare efficacy of BIBF 1120 to Sorafenib in HCC patients

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose in Phase I

  The MTD was defined as the highest dose studied for which the incidence of dose limiting toxicities (DLTs) was 0/3 or less than 2/6 patients during the first treatment course.

  4 weeks

• Time to Progression (TTP) in Phase II

  TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.

  From randomization until data cut-off (15 July 2014); Up to 1031 days

Secondary Outcomes (4)

• Incidence of Dose Limiting Toxicity in Phase I

  4 weeks

• Objective Tumour Response by RECIST

  From randomization until data cut-off (15 July 2014); Up to 1031 days

• Progression Free Survival (PFS)

  From randomization until data cut-off (15 July 2014); Up to 1031 days

• Overall Survival

  From randomization until data cut-off (15 July 2014); Up to 1031 days

Study Arms (2)

BIBF 1120

EXPERIMENTAL

Phase I dose escalation and phase II using dose determined in phase I ( 200 mg BID)

Drug: BIBF 1120

Sorafenib

ACTIVE COMPARATOR

Drug: Sorafenib

Interventions

Sorafenib DRUG

Sorafenib

BIBF 1120 DRUG

Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data

BIBF 1120

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC) not amenable to curative surgery or loco-regional therapy (RFA, percutaneous ethanol injection (PEI), TACE)
• Age 18 years or older
• Eastern Cooperative Oncology Group performance score of 2 or less
• Child-Pugh score A (score 5-6)
• At least one measurable lesion according to RECIST 1.0 (this criterion is limited to phase II only)
• In case a measurable lesion was previously treated by loco-regional therapy (RFA, PEI, TACE or RT) , this lesion must have to be documented as progression according to RECIST 1.0 by CT or MRI (this criterion is limited to phase II only).
• Time interval from last local therapy (e.g. radiofrequency ablation, percutaneous ethanol injection, radiotherapy, transarterial chemoembolization) more than 4 weeks prior to start of study treatment
• Written informed consent consistent with International Conference on Harmonisation/ Good Clinical Practice (ICH-GCP) and local legislation

You may not qualify if:

• Prior systemic therapy for HCC
• Fibrolamellar hepatocellular carcinoma (HCC)
• Bilirubin greater than 1.5 times ULN
• AST or ALT greater than 2 times ULN
• Uncontrolled or refractory ascites to adequate medical therapy
• Hepatic encephalopathy more than grade 1 according to Child-Pugh criteria
• Prothrombin time international normalized ratio greater than 2.3, or prothrombin time more than 6 seconds prolonged than control
• Absolute neutrophil count less than 1000 /µL
• Platelet count less than 60000 /µL
• Hemoglobin less than 9 g/dL
• Serum creatinine greater than 1.5 times Upper Limit of Normal (ULN)
• Proteinuria of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater
• Variceal bleeding within last 6 months prior to start of study treatment
• History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months
• Known inherited predisposition to bleeding or thrombosis

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (28)

1199.37.43001 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

1199.37.43002 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

1199.37.33001 Boehringer Ingelheim Investigational Site

Paris, France

Location

1199.37.33002 Boehringer Ingelheim Investigational Site

Paris, France

Location

1199.37.49008 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1199.37.49009 Boehringer Ingelheim Investigational Site

Erlangen, Germany

Location

1199.37.49002 Boehringer Ingelheim Investigational Site

Freiburg im Breisgau, Germany

Location

1199.37.49001 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1199.37.49010 Boehringer Ingelheim Investigational Site

Heidelberg, Germany

Location

1199.37.49005 Boehringer Ingelheim Investigational Site

Jena, Germany

Location

1199.37.49004 Boehringer Ingelheim Investigational Site

Magdeburg, Germany

Location

1199.37.49003 Boehringer Ingelheim Investigational Site

München, Germany

Location

1199.37.49006 Boehringer Ingelheim Investigational Site

Tübingen, Germany

Location

1199.37.36001 Boehringer Ingelheim Investigational Site

Debrecen, Hungary

Location

1199.37.31002 Boehringer Ingelheim Investigational Site

Leiden, Netherlands

Location

1199.37.31001 Boehringer Ingelheim Investigational Site

Utrecht, Netherlands

Location

1199.37.48002 Boehringer Ingelheim Investigational Site

Olsztyn, Poland

Location

1199.37.48001 Boehringer Ingelheim Investigational Site

Warsaw, Poland

Location

1199.37.48003 Boehringer Ingelheim Investigational Site

Warsaw, Poland

Location

1199.37.40002 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

1199.37.40003 Boehringer Ingelheim Investigational Site

Cluj-Napoca, Romania

Location

1199.37.44001 Boehringer Ingelheim Investigational Site

Edgbaston, Birmingham, United Kingdom

Location

1199.37.44005 Boehringer Ingelheim Investigational Site

Glasgow, United Kingdom

Location

1199.37.44008 Boehringer Ingelheim Investigational Site

Liverpool, United Kingdom

Location

1199.37.44002 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1199.37.44003 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1199.37.44006 Boehringer Ingelheim Investigational Site

Manchester, United Kingdom

Location

1199.37.44004 Boehringer Ingelheim Investigational Site

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib; nintedanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

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

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2009
• First Posted: October 29, 2009
• Study Start: October 22, 2009
• Primary Completion: July 14, 2014
• Study Completion: October 12, 2016
• Last Updated: October 26, 2017
• Results First Posted: August 7, 2015

Record last verified: 2017-09

Locations

PL (3); GB (7); AU (2); RO (2); FR (2); DE (9); NL (2); HU (1)