Breast NeoplasmsPhase 1NCT00950742

Phase I Open Label Trial to Assess Safety of BIBW 2992 (Afatinib) in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.

A Phase 1 study testing Trastuzumab and BIBW 2992 in people with Breast Neoplasms, run by Boehringer Ingelheim at 5 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Study to determine the Maximum Tolerated dose of BIBW 2992 given in combination with Herceptin® Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Neoplasms
What is being tested?: Trastuzumab and BIBW 2992
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 5 sitesUnited Kingdom
Study dates: 1 Aug 2009to 1 Oct 2013
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Female patients aged >18 years.
Advanced or metastatic breast cancer that over-expresses HER2 (immunohistochemistry 3+ or 2+ and gene amplification by FISH). Prior treatment with Herceptin® or Lapatinib® (in the adjuvant or metastatic settings) is permitted but not required.

Who cannot join

Patients with untreated or symptomatic brain metastases. Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past four weeks before the start of therapy or concomitantly with this study.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United Kingdom5 sites

1200.68.44001 Boehringer Ingelheim Investigational Site
Brighton
1200.68.44003 Boehringer Ingelheim Investigational Site
Cambridge
1200.68.44005 Boehringer Ingelheim Investigational Site
Guildford
1200.68.44004 Boehringer Ingelheim Investigational Site
Newcastle upon Tyne
1200.68.44002 Boehringer Ingelheim Investigational Site
Truro

Other trials in United Kingdom

About this study

Official title: Phase I Open Label Trial to Assess Safety of BIBW 2992 in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.

Study to determine the Maximum Tolerated dose of BIBW 2992 given in combination with Herceptin®

Conditions: Breast Neoplasms
Being tested: Trastuzumab, BIBW 2992
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TrastuzumabDrug
Load: 4mg/kg-maintain:2mg/kg/week
BIBW 2992Drug
Increased dose cohorts from low dose to MTD

Study groups in NCT00950742
Study group	Role	What they receive
BIBW 2992 + Trastuzumab	Experimental	Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally with fixed weekly infusion doses of 2mg/kg Herceptin. Escalating doses of BIBW 2992 starting at 20mg daily. Receives: Drug: Trastuzumab; Drug: BIBW 2992

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose Limiting Toxicities (DLT)
Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD). Important Limitations and Caveats are provided in the respective section.
Measured: 28 days
Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R)
The MTD was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. It was determined using a standard 3 + 3 dose escalation cohort design. To confirm the MTD, the MTD cohort was to be expanded to 18 patients with no more than 3/18 patients experiencing a DLT. Please refer to CAVEATs and Limitations.
Measured: 28 days

Secondary outcomes (6)

Number of Patients With Objective Response (OR)
Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR).
Measured: Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.
Number of Patients With Best Overall Response
Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or not evaluable.
Measured: Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.
Progression Free Survival (PFS)
PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the response evaluation criteria in solid tumors (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.
Measured: Baseline until disease progression, death or data cut-off.
Summary of Concentration of Afatinib in Plasma
Pre-dose Concentrations of Afatinib in Plasma at Steady State on Days 8, 15 and 29 (Cpre,ss,8, Cpre,ss,15 and Cpre,ss,29) and Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss).
Measured: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing
Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)
tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state
Measured: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing
Summary of Concentration of Herceptin in Plasma
Pre-dose Concentrations of Herceptin in Plasma on Days 8, 15 and 29 (Cpre,8, Cpre,15 and Cpre,29) and Maximum Concentration of Herceptin in Plasma on Days 1, 15 and 29 (Cmax,1, Cmax,15 and Cmax,29).
Measured: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Aug 20091 Oct 2013

First posted3 Aug 2009 (estimated)
Study start1 Aug 2009
Primary completion1 Oct 2013
Study completion1 Oct 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00950742
Sponsor's protocol ID: 1200.68
Other IDs: 2009-010003-89, 2009
Status last verified: Jan 2025
First submitted: 31 Jul 2009
Last updated: 10 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Breast Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Open Label Trial to Assess Safety of BIBW 2992 in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.
ClinicalTrials.gov ID: NCT00950742
Acronym / sponsor ID: 1200.68
Conditions: Breast Neoplasms
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 1 Aug 2009 (actual)
Primary completion: 1 Oct 2013 (actual)
Study completion: 1 Oct 2013 (actual)
First posted: 3 Aug 2009 (estimated)
Results: Posted 17 Oct 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study to determine the Maximum Tolerated dose of BIBW 2992 given in combination with Herceptin®

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BIBW 2992 + Trastuzumab	Experimental	Drug: Trastuzumab, Drug: BIBW 2992Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally with fixed weekly infusion doses of 2mg/kg Herceptin. Escalating doses of BIBW 2992 starting at 20mg daily.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Female patients aged >18 years.
Advanced or metastatic breast cancer that over-expresses HER2 (immunohistochemistry 3+ or 2+ and gene amplification by FISH). Prior treatment with Herceptin® or Lapatinib® (in the adjuvant or metastatic settings) is permitted but not required.

Key exclusion criteria (1 listed)

Patients with untreated or symptomatic brain metastases. Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past four weeks before the start of therapy or concomitantly with this study.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TrastuzumabLoad: 4mg/kg-maintain:2mg/kg/week	Drug	BIBW 2992 + Trastuzumab
BIBW 2992Increased dose cohorts from low dose to MTD	Drug	BIBW 2992 + Trastuzumab

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLT)
Time frame: 28 days
Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD). Important Limitations and Caveats are provided in the respective section.
Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R)
Time frame: 28 days
The MTD was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. It was determined using a standard 3 + 3 dose escalation cohort design. To confirm the MTD, the MTD cohort was to be expanded to 18 patients with no more than 3/18 patients experiencing a DLT. Please refer to CAVEATs and Limitations.

6 secondary outcomes

Number of Patients With Objective Response (OR)
Time frame: Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.
Number of Patients With Best Overall Response
Time frame: Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.
Progression Free Survival (PFS)
Time frame: Baseline until disease progression, death or data cut-off.
Summary of Concentration of Afatinib in Plasma
Time frame: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing
Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)
Time frame: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing
Summary of Concentration of Herceptin in Plasma
Time frame: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing

Results and safety

Results posted to the registry on 17 Oct 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Afatinib 20mg + Herceptin	16	0
Afatinib 30mg + Herceptin	2	0

Primary outcome: Number of Participants With Dose Limiting Toxicities (DLT)

Time frame: 28 days. Number. Unit: Participants

Measure	Afatinib 20mg + Herceptin n = 13	Afatinib 30mg + Herceptin n = 2
Value	4	2

Population analysed: Treated set (TS). TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. 3 patients were excluded as they were not evaluable for determination of maximum tolerated dose.

Primary outcome: Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R)

Time frame: 28 days. Number. Unit: mg

Measure	Afatinib n = 8
Value	20

Population analysed: TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. 3 patients were excluded as they were not evaluable for determination of maximum tolerated dose.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: First administration of trial medication until 28 days after last administration of trial medication (up to 1296 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Afatinib 20mg + Herceptin	3 of 16 (18.8%)	15 of 16 (93.8%)	Not reported
Afatinib 30mg + Herceptin	0 of 2 (0%)	2 of 2 (100%)	Not reported

Limitations and caveats (from the sponsor): MTD was determined at 20mg afatinib when 1/6 pat. had DLT (3+3 design). Upon expansion of MTD cohort to 18 pat. recruitment was stopped when 4/13 pat. had DLT. No lower afatinib dose could be tested as 20mg was the lowest dose formulation available.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Trastuzumab and BIBW 2992 in people with Breast Neoplasms, run by Boehringer Ingelheim at 5 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLT) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00950742.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.