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

July 23, 2015 updated by: Boehringer Ingelheim
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif Cedex, France
        • 1239.14.3301A Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. 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.
  2. Age 18 years or older.
  3. Life expectancy of at least three months.
  4. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
  5. Patients previously treated and with asymptomatic brain metastases are eligible
  6. Patients must have recovered from recent surgery.

Exclusion criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BIBW 2992 + BIBF 1120
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: BIBF 1120
VEGF inhibitor
Drug: BIBW 2992
EGFR inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities
Time Frame: first treatment cycle, up to 28 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Tumour Response Rate Assessed by the Investigator According to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1
Time Frame: 6 weeks

The investigator evaluated whether complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) occurred in a patient.

CR for target lesions: Disappearance of all target lesions. CR for non-target lesions: Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis).

PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters.

SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest SoD while on study.

PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions
6 weeks
Incidence and Intensity of Adverse Events According to CTCAE (Common Toxicity Criteria Adverse Event) Version 3.0
Time Frame: First treatment administration until cut-off date of 02Oct2014; up to 336 days
Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).
First treatment administration until cut-off date of 02Oct2014; up to 336 days
Changes in Safety Laboratory Parameters
Time Frame: First treatment administration until cut-off date of 02 October 2014, up to 336 days
Changes in safety laboratory Parameters reported as adverse events
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)
Time Frame: Day 8, Day 15, Day 22 and Day 28

Cpre,ss,norm (Dose normalized trough plasma concentration of nintedanib at steady state) are presented for the 2 MTD treatment groups (continuous administered nintedanib at 150 mg b.i.d. concomitantly with continuously administered afatinib 30 mg q.d. or with intermittently administered afatinib 40 mg q.d.)

As nintedanib is given twice daily, samples are taken at Day 8, Day 15, Day 22 and Day 28; the Pharmacokinetic (PK) parameter names will be Cpre,ss,15,norm (Day 8), Cpre,ss,29,norm (Day 15), Cpre,ss,43,norm (Day 22) and Cpre,ss,55,norm (Day 28)
Day 8, Day 15, Day 22 and Day 28
Trough Plasma Concentration of Afatinib at Steady State
Time Frame: Day 7, Day 13, Day 15, Day 22, Day 27 and Day 28

C(pre,ss) is defined as pre-dose (trough) concentration of afatinib in plasma at steady state immediately before administration of the next dose.

C24,7 corresponds to the plasma concentration at 24 hours on Day 7. C24,13 corresponds to the plasma concentration at 24 hours on Day 13. C24,27 corresponds to the plasma concentration at 24 hours on Day 27.
Day 7, Day 13, Day 15, Day 22, Day 27 and Day 28
Objective Response (OR) During the Expansion Phase
Time Frame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)

OR is defined as a best overall response of complete response (CR) or partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions.

CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be nonpathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

Other factors which add to the overall response of an imaging timepoint as PR are as below:

CR in TL, but non-CR/Non-PD in NTL leads to PR CR in TL, but not evaluated NTL leads to PR PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; All the above scenarios should also satisfy 'No occurrence of new lesions'.
Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
Disease Control (DC) During the Expansion Phase
Time Frame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD. CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (<10mm short axis). PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- CR in TL, but non-CR/Non-PD in NTL leads to PR CR in TL, but not evaluated NTL leads to PR PR in TL, but non-PD NTL or not all evaluated NTL leads to PR; SD for TL: change in the sum of diameters does not satisfy PR or PD. SD in TL, non-PD in NTL lead to overall response of SD, provided there is no appearance of new lesions.
Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
Stable Disease for at Least 12 Weeks During the Expansion Phase
Time Frame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)

SD: Neither sufficient shrinkage to qualify for PR (Partial response) nor sufficient increase to qualify for PD(Progressive disease), taking as references the smallest sum of diameters SoD while on study.

PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters.

PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions.
Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
Percentage Change in the Tumour Size From Baseline During the Expansion Phase
Time Frame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
Percentage change in the tumour size from baseline is expressed as Number of subjects with maximum decrease from baseline in the sum of longest diameters of target lesions.
Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

October 19, 2009

First Submitted That Met QC Criteria

October 19, 2009

First Posted (Estimate)

October 20, 2009

Study Record Updates

Last Update Posted (Estimate)

August 19, 2015

Last Update Submitted That Met QC Criteria

July 23, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1239.14
  • 2009-011321-14 (EudraCT Number: EudraCT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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