Dose Escalation Study of Oral Treatment With BIBW 2992 in Patients With Advanced Solid Tumours

June 20, 2014 updated by: Boehringer Ingelheim

A Phase I Open Label Dose Escalation Study of Once-daily Oral Treatment With BIBW 2992 for 28 Days in Patients With Advanced Solid Tumours

The primary objective of the study was to identify the maximum tolerated dose and to evaluate safety, pharmacokinetics, pharmacodynamic parameters, and efficacy of BIBW 2992.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
53

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female patients with confirmed diagnosis of advanced, non-resectable and / or metastatic solid tumours, of types historically known to express EGFR and/or HER2, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment preferably patients with breast, colorectal or prostate cancer
  • Age 18 years or older
  • Life expectancy of at least three (3) months
  • Written informed consent that is consistent with International Conference on Harmonization - Good Clinical Practice guidelines
  • Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2
  • Patients completely recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies to CTC <= Grade 1
  • Patients must be recovered from previous surgery

The 12 additional patients recruited at the MTD must also meet the following criteria:

  • Measurable tumour deposits (RECIST) by one or more techniques (X-ray, CT, MRI) and/or recognized tumour markers such as prostate-specific antigen prostate cancer) or cancer antigen 125 (Ovarian cancer)

Exclusion Criteria:

  • Active infectious disease
  • Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea
  • Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
  • Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least eight (8) weeks, no history of cerebral edema or bleeding in the past eight (8) weeks and no requirement for steroids or anti-epileptic therapy
  • Cardiac left ventricular function with resting ejection fraction CTC >= Grade 1
  • Absolute neutrophil count (ANC) less than 1500 / mm3
  • Platelet count less than 100 000 / mm3
  • Bilirubin greater than 1.5 mg /dl (>26 μmol /L, Système Internationale (SI) unit equivalent)
  • Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
  • Serum creatinine greater than 1.5 mg / dl (>132 μmol / L, SI unit equivalent)
  • Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
  • Pregnancy or breast-feeding
  • Treatment with other investigational drugs; chemotherapy, immunotherapy, radiotherapy or hormone therapy (excluding Luteinizing Hormone-Releasing Hormone agonists, or other hormones taken for breast cancer, or bisphosphonates), or participation in another clinical study within the past 4 weeks before start of therapy or concomitantly with this study
  • Treatment with an EGFR- or HER2 inhibiting drug within the past four weeks before start of therapy or concomitantly with this study (8 weeks for trastuzumab)
  • Patients unable to comply with the protocol
  • Active alcohol or drug abuse

A patient may be eligible for re-treatment after the previous course is finished. A patient will not be eligible if any of the following conditions are met.

  • Patients with clinical signs of disease progression or if latest X-ray, CT or MRI reveals Progressive Disease
  • Cardiac left ventricular function CTC >= Grade 2 at any time during the previous course
  • Patients fulfilling any of the Exclusion Criteria listed before as determined before treatment on Day 28, R5 of the previous course
  • Patient not recovered from any dose-limiting toxicity 14 days after the last administration of BIBW 2992 in the previous course. Recovery is defined as return to baseline level or CTC Grade 1, whichever is higher

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: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: BIBW 2992
dose escalation
Drug: BIBW 2992
Experimental: BIBW 2992, fasted
food effect part: maximum tolerated dose of BIBW 2992
Drug: BIBW 2992
Experimental: BIBW 2992, fed
food effect part: maximum tolerated dose of BIBW 2992
Drug: BIBW 2992

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Maximum tolerated dose (MTD) of BIBW 2992
Time Frame: up to 24 weeks
up to 24 weeks
Incidence and intensity of Adverse Events according to Common Toxicity Criteria (CTC version 3) associated with increasing doses of BIBW 2992
Time Frame: up to 28 weeks
up to 28 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Area under the plasma concentration-time curve (AUC) for several time points
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
Percentage of AUC0-∞ that is obtained by extrapolation (%AUCtz-∞)
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
predose plasma concentration
Time Frame: predose on days 8, 15, 22 and 27
predose on days 8, 15, 22 and 27
Plasma concentration
Time Frame: 24 hours after drug administration on the first (C24,1) and the Day 27 dose (C24,27)
24 hours after drug administration on the first (C24,1) and the Day 27 dose (C24,27)
Maximum measured plasma concentration (Cmax) for several time points
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
Time from dosing to the maximum plasma concentration (tmax) for several time points
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
terminal half-life (t1/2(ss))
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
mean residence time after oral administration (MRTpo(ss))
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
apparent clearance (CL/F(ss))
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
apparent volume of distribution during the terminal phase (Vz/F(ss))
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
Accumulation ratio between Day 1 and Day 27 with respect to Cmax (RA1) and AUC (RA2)
Time Frame: up to 648 hours after first drug administration, pre-dose on day 15 and 28
up to 648 hours after first drug administration, pre-dose on day 15 and 28
Modulation of biomarker (EGFR, p-EGFR, p-MAPK, p-Akt, Ki 67, p-27KIP1) in skin biopsies
Time Frame: Baseline and day 28 of the first treatment period
Baseline and day 28 of the first treatment period
Modulation of biomarker (EGFR, p-EGFR, HER2 (Class I Tyrosine Kinase Receptor), p-MAPK (mitogen-activated protein kinase), p-Akt, Ki 67, p-27KIP1) in tumour biopsies in six or more patients treated at the MTD
Time Frame: Baseline and day 28 of the first treatment period
Baseline and day 28 of the first treatment period
Objective tumour response
Time Frame: up to 25 weeks
up to 25 weeks
Correlation of EGFR, HER2, estrogen receptor (ER) and progesterone receptor (PrR) immunohistochemical status as based on tumour biopsies, or excisions obtained prior to this study, with objective tumour responses
Time Frame: up to 25 weeks
up to 25 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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.

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2007

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 20, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 24, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1200.3

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