Phase I Dose Escalation Study of Concomitant BIBF 1120 and BIBW 2992 in Patients With Advanced Solid Tumours.

NCT00998296 | Completed Phase 1 Results

• 2 other identifiers: 1239.142009-011321-14
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this trial is to determine the Maximum Tolerated Dose (MTD) of the combination of BIBW 2992/BIBF 1120 therapy administered concomitantly. The MTD will provide dosing recommendation for subsequent phase II trials in patients with metastatic cancer.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities

  Maximum tolerated dose (MTD) of nintedanib and afatinib based on the Percentage of participants experienced dose limiting toxicities during the dose escalation phase.

  first treatment cycle, up to 28 days

Secondary Outcomes (9)

• Overall Tumour Response Rate Assessed by the Investigator According to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1

  6 weeks

• Incidence and Intensity of Adverse Events According to CTCAE (Common Toxicity Criteria Adverse Event) Version 3.0

  First treatment administration until cut-off date of 02Oct2014; up to 336 days

• Changes in Safety Laboratory Parameters

  First treatment administration until cut-off date of 02 October 2014, up to 336 days

• Cpre,ss,Norm (Dose Normalized Trough Plasma Concentration of Nintedanib at Steady State)

  Day 8, Day 15, Day 22 and Day 28

• Trough Plasma Concentration of Afatinib at Steady State

  Day 7, Day 13, Day 15, Day 22, Day 27 and Day 28

Study Arms (1)

BIBW 2992 + BIBF 1120

EXPERIMENTAL

This is a phase I dose escalation clinical trial and the data obtained shall determine the MTD for the combination of BIBW 2992/BIBF 1120 in 28-day of treatment.

Drug: BIBW 2992; Drug: BIBF 1120

Interventions

BIBW 2992 DRUG

EGFR inhibitor

BIBW 2992 + BIBF 1120

BIBF 1120 DRUG

VEGF inhibitor

BIBW 2992 + BIBF 1120

Eligibility Criteria

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

You may qualify if:

• Patients with confirmed histological or cytological diagnosis of advanced solid tumours and for whom no proven therapy exists or who are not amenable to established treatments.
• Age 18 years or older.
• Life expectancy of at least three months.
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
• Patients previously treated and with asymptomatic brain metastases are eligible
• Patients must have recovered from recent surgery.

You may not qualify if:

• Active infectious disease
• Recent surgery within the last 4 weeks prior visit 1.
• Chronic diarrhoea or gastrointestinal tract disease resulting in an inability to take oral medication
• History of haemorrhagic or thrombotic events
• Significant cardiovascular diseases within
• Current peripheral neuropathy \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1 except due to trauma
• Untreated or symptomatic brain metastases or leptomeningeal disease.
• Treatment with an Epidermal growth Factor-receptor (EGFR)- or Heregulin Receptor 2 (HER2) inhibiting drug or antiangiogenic drug.
• Therapeutic anticoagulation.
• Female patients of childbearing potential.
• Known pre-existing interstitial lung disease

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1239.14.3301A Boehringer Ingelheim Investigational Site

Villejuif, France

Location

Related Publications (1)

• Bahleda R, Hollebecque A, Varga A, Gazzah A, Massard C, Deutsch E, Amellal N, Farace F, Ould-Kaci M, Roux F, Marzin K, Soria JC. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours. Br J Cancer. 2015 Nov 17;113(10):1413-20. doi: 10.1038/bjc.2015.374. Epub 2015 Oct 29.

  PMID: 26512876 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Afatinib; nintedanib

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2009
• First Posted: October 20, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: July 1, 2014
• Last Updated: August 19, 2015
• Results First Posted: February 9, 2015

Record last verified: 2015-07

Locations

FR (1)