Breast NeoplasmsPhase 2NCT00708214

BIBW 2992 and Letrozole in Hormonoresistant Metastatic Breast Cancer

A Phase 2 study testing BIBW 2992 and Letrozole in people with Breast Neoplasms, run by Boehringer Ingelheim at 5 sites in France.

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

Progression-free rate after 16 weeks of BIBW 2992 administration in association with letrozole 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?: BIBW 2992 and Letrozole
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 5 sitesFrance
Study dates: Jan 2007to Feb 2010
Phase: Phase 2
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 with histologically proven breast adenocarcinoma
Presence of metastatic disease No more than 2 prior chemotherapy regimens for metastatic disease, which could include trastuzumab Patients must currently be on letrozole and developed acquired resistance as defined by disease progression on letrozole following previous response (partial response or better, stable disease superior or equal to 24 weeks)
Diagnosis of disease progression inferior or equal to 6 weeks prior to trial entrydefined as:
Increase in the number of bone lesions on bone scan or on MRI AND/OR
Increased pain in an area of known bony metastasis AND superior or equal to 2 serial elevations in CA 15.3 AND/OR
Progression according to RECIST criteria on CT scan, MRI, or x-ray Patients must have documented menopause confirmed by estradiol level inferior to 11 pg/ml

Who cannot join

Premenopausal patients
Rapidly progressive disease in major organs (i.e. lymphangitic spread in the lung and/or bulky liver metastasis) Patient with brain metastasis Significant cardiovascular diseases Previous treatment with an EGFR and/or HER-2 inhibiting drug(patients who received trastuzumab with chemotherapy but not with letrozole can be enrolled)

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

France5 sites

1200.5.3306A Boehringer Ingelheim Investigational Site
Caen
1200.5.3304A Boehringer Ingelheim Investigational Site
Nice
1200.5.3301A Boehringer Ingelheim Investigational Site
Paris
1200.5.3305A Boehringer Ingelheim Investigational Site
Paris
1200.5.3302A Boehringer Ingelheim Investigational Site
Saint-Cloud

Other trials in France

About this study

Official title: A Phase II Study of BIBW 2992 Administration in Patients With Hormone Refractory Metastatic Breast Cancer

Progression-free rate after 16 weeks of BIBW 2992 administration in association with letrozole

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

What participants receive

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

BIBW 2992Drug
BIBW 2992 at high and medium dosages
BIBW 2992Drug
BIBW 2992 at high and medium dosages
LetrozoleDrug
Letrozole at standard dosage
LetrozoleDrug
Letrozole at standard dosage

Study groups in NCT00708214
Study group	Role	What they receive
BIBW 2992	Experimental	To study BIBW 2992 in association with letrozole in hormonoresistant metastatic breast cancer Receives: Drug: BIBW 2992; Drug: Letrozole
Letrozole	Other	Hormonotherapy for metastatic breast cancer Receives: Drug: BIBW 2992; Drug: Letrozole

What is being measured

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

Percentage of Progression Free Participants After 16 Weeks of Treatment
Progression was defined according to 1 of the following criteria: New bone lesion(s) on bone scan or on magnetic resonance imaging; Progression or occurrence of new lesion(s) according to the Response Evaluation Criteria In Solid Tumours version 1.0 (RECIST); an increase in tumour marker CA 15.3 of more than 20 percent,compared with baseline, at 2 consecutive examinations; occurrence of disease-related skeletal events. If a patient did not fulfil any criteria and was withdrawn because of clinical deterioration amounting to PD according to the Investigator, they were considered as having PD.
Measured: 16 weeks

Secondary outcomes (16)

Number of Participants With Confirmed Objective Response (OR)
OR was defined as complete response (CR) or partial response (PR) and was assessed according to RECIST criteria regardless of treatment status.
Measured: Baseline till progression
Number of Participants With Clinical Benefit (CB)
CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status.
Measured: 16 weeks and 24 weeks
Time to RECIST Tumour Reponse
The time to OR was the duration from the first treatment to the time when the measurement criteria for CR and/or PR were met according to RECIST criteria.
Measured: Baseline till progression
Duration of Confirmed OR
Duration of confirmed OR is measured from the time of first OR to the time of progression or death (or date of censoring for progression free survival).
Measured: First occurence or OR till progression or death
Progression-free Survival (PFS)
PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. Progression was assessed according to RECIST criteria.
Measured: Baseline till progression, death or data cut-off (04 Jan 2010)
Overall Survival (OS)
OS was defined as the time from first treatment to death.
Measured: Baseline till progression, death or data cut-off
Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)
AUCtau,ss represents the area under the concentration curve of afatinib in plasma over a uniform dosing interval tau at steady state.
Measured: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)
Cmax,ss represents the maximum measured concentration of afatinib in plasma at steady state.
Measured: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 57 (Cpre,ss,57)
Cpre,ss,57 represents the pre-dose concentration of afatinib in plasma at steady state on day 57.
Measured: Day 57
Pre-dose Concentration of Afatinib in Plasma at Steady Stateon Day 85 (Cpre,ss,85)
Cpre,ss,85 represents the pre-dose concentration of afatinib in plasma at steady state on day 85.
Measured: Day 85
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 2h, 4h, 6h, 8h and 24h after dosing
Area Under Curve of Letrozole Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)
AUC0-tau,ss represents the area under the concentration curve of letrozole in plasma over a uniform dosing interval tau at steady state.
Measured: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Maximum Concentration of Letrozole in Plasma at Steady State (Cmax,ss)
Cmax,ss represents the maximum measured concentration of letrozole in plasma at steady state.
Measured: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Time From Dosing to the Maximum Concentration of Letrozole in Plasma at Steady State (Tmax,ss)
tmax,ss represents the time from dosing to the maximum concentration of letrozole in plasma at steady state.
Measured: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Change From Baseline in Ca15.3
Change from baseline in Ca15.3 tumor marker levels
Measured: baseline and day 29
Best Change From Baseline in ECOG Performance Status
Best change from baseline in ECOG (Eastern Cooperative Oncology Group) performance status. ECOG is measured as score between 0 (fully active) and 5 (dead). Improvement is a decrease in ECOG score from baseline of at least 1. Deterioration is an increase in ECOG score from baseline of at least 1
Measured: baseline till end of treatment

Timeline

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

Jan 2007Feb 2010

First posted2 Jul 2008 (estimated)
Study startJan 2007
Primary completionFeb 2010

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.
Publications (1)Papers the sponsor has linked to this study.
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 2
Primary purpose: Treatment
Allocation: Non-randomised
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00708214
Sponsor's protocol ID: 1200.5
Other IDs: 2006-002814-37
Status last verified: Oct 2013
First submitted: 30 Jun 2008
Last updated: 30 Dec 2013
Results posted: Yes, on ClinicalTrials.gov

Publications

Gunzer K, Joly F, Ferrero JM, Gligorov J, de Mont-Serrat H, Uttenreuther-Fischer M, Pelling K, Wind S, Bousquet G, Misset JL. A phase II study of afatinib, an irreversible ErbB family blocker, added to letrozole in patients with estrogen receptor-positive hormone-refractory metastatic breast cancer progressing on letrozole. Springerplus. 2016 Jan 19;5:45. doi: 10.1186/s40064-015-1601-7. eCollection 2016.
PubMed 26835225

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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Study at a glance

From the registry record, last updated by the sponsor on 30 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Study of BIBW 2992 Administration in Patients With Hormone Refractory Metastatic Breast Cancer
ClinicalTrials.gov ID: NCT00708214
Acronym / sponsor ID: 1200.5
Conditions: Breast Neoplasms
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Jan 2007
Primary completion: Feb 2010 (actual)
First posted: 2 Jul 2008 (estimated)
Results: Posted 19 Nov 2013

Clinical summary

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

Progression-free rate after 16 weeks of BIBW 2992 administration in association with letrozole

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
BIBW 2992	Experimental	Drug: BIBW 2992, Drug: LetrozoleTo study BIBW 2992 in association with letrozole in hormonoresistant metastatic breast cancer
Letrozole	Other	Drug: BIBW 2992, Drug: LetrozoleHormonotherapy for metastatic breast cancer

Who may qualify

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

Key inclusion criteria (6 listed)

Female patients with histologically proven breast adenocarcinoma
Presence of metastatic disease No more than 2 prior chemotherapy regimens for metastatic disease, which could include trastuzumab Patients must currently be on letrozole and developed acquired resistance as defined by disease progression on letrozole following previous response (partial response or better, stable disease superior or equal to 24 weeks)
Diagnosis of disease progression inferior or equal to 6 weeks prior to trial entrydefined as:
Increase in the number of bone lesions on bone scan or on MRI AND/OR
Increased pain in an area of known bony metastasis AND superior or equal to 2 serial elevations in CA 15.3 AND/OR

Key exclusion criteria (2 listed)

Premenopausal patients
Rapidly progressive disease in major organs (i.e. lymphangitic spread in the lung and/or bulky liver metastasis) Patient with brain metastasis Significant cardiovascular diseases Previous treatment with an EGFR and/or HER-2 inhibiting drug(patients who received trastuzumab with chemotherapy but not with letrozole can be enrolled)

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
BIBW 2992BIBW 2992 at high and medium dosages	Drug	BIBW 2992
BIBW 2992BIBW 2992 at high and medium dosages	Drug	Letrozole
LetrozoleLetrozole at standard dosage	Drug	BIBW 2992
LetrozoleLetrozole at standard dosage	Drug	Letrozole

Primary outcome

Percentage of Progression Free Participants After 16 Weeks of Treatment
Time frame: 16 weeks
Progression was defined according to 1 of the following criteria: New bone lesion(s) on bone scan or on magnetic resonance imaging; Progression or occurrence of new lesion(s) according to the Response Evaluation Criteria In Solid Tumours version 1.0 (RECIST); an increase in tumour marker CA 15.3 of more than 20 percent,compared with baseline, at 2 consecutive examinations; occurrence of disease-related skeletal events. If a patient did not fulfil any criteria and was withdrawn because of clinical deterioration amounting to PD according to the Investigator, they were considered as having PD.

16 secondary outcomes

Number of Participants With Confirmed Objective Response (OR)
Time frame: Baseline till progression
Number of Participants With Clinical Benefit (CB)
Time frame: 16 weeks and 24 weeks
Time to RECIST Tumour Reponse
Time frame: Baseline till progression
Duration of Confirmed OR
Time frame: First occurence or OR till progression or death
Progression-free Survival (PFS)
Time frame: Baseline till progression, death or data cut-off (04 Jan 2010)
Overall Survival (OS)
Time frame: Baseline till progression, death or data cut-off
Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)
Time frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)
Time frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 57 (Cpre,ss,57)
Time frame: Day 57
Pre-dose Concentration of Afatinib in Plasma at Steady Stateon Day 85 (Cpre,ss,85)
Time frame: Day 85
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 2h, 4h, 6h, 8h and 24h after dosing
Area Under Curve of Letrozole Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)
Time frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Maximum Concentration of Letrozole in Plasma at Steady State (Cmax,ss)
Time frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Time From Dosing to the Maximum Concentration of Letrozole in Plasma at Steady State (Tmax,ss)
Time frame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
Change From Baseline in Ca15.3
Time frame: baseline and day 29
Best Change From Baseline in ECOG Performance Status
Time frame: baseline till end of treatment

Results and safety

Results posted to the registry on 19 Nov 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 50 mg With Letrozole	7	0
Afatinib 40 mg With Letrozole	13	0
Afatinib 30 mg With Letrozole	8	0

Primary outcome: Percentage of Progression Free Participants After 16 Weeks of Treatment

Time frame: 16 weeks. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Afatinib 50 mg With Letrozole n = 7	Afatinib 40 mg With Letrozole n = 13	Afatinib 30 mg With Letrozole n = 8
Value	28.57 (3.67 to 70.96)	0.00 (0.00 to 24.71)	25.00 (3.19 to 65.09)

Population analysed: Treated set (TS). TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib.

16 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. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Afatinib 50 mg With Letrozole	1 of 7 (14.3%)	7 of 7 (100%)	Not reported
Afatinib 40 mg With Letrozole	3 of 13 (23.1%)	13 of 13 (100%)	Not reported
Afatinib 30 mg With Letrozole	5 of 8 (62.5%)	8 of 8 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26835225Gunzer K, Joly F, Ferrero JM, Gligorov J, de Mont-Serrat H, Uttenreuther-Fischer M, Pelling K, Wind S, Bousquet G, Misset JL. A phase II study of afatinib, an irreversible ErbB family blocker, added to letrozole in patients with estrogen receptor-positive hormone-refractory metastatic breast cancer progressing on letrozole. Springerplus. 2016 Jan 19;5:45. doi: 10.1186/s40064-015-1601-7. eCollection 2016.
Related InfoLink provided by the sponsor.
Related InfoLink provided by the sponsor.

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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 2 study testing BIBW 2992 and Letrozole in people with Breast Neoplasms, run by Boehringer Ingelheim at 5 sites in France.

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 6 inclusion and 2 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 30 Dec 2013. 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 France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 19 Nov 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?

Percentage of Progression Free Participants After 16 Weeks of Treatment (time frame: 16 weeks). 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 NCT00708214, which also lists 1 linked publication.

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 30 Dec 2013.