Breast NeoplasmsPhase 1NCT01649271

Phase I Trial of Afatinib and Trastuzumab in HER2 Overexpressing Cancer.

A Phase 1 study testing Herceptin, afatinib and trastuzumab in people with Breast Neoplasms and Stomach Neoplasms, run by Boehringer Ingelheim at 3 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

The aim of the study is to determine the Maximum Tolerated Dose (MTD) of afatinib in combination with 3-weekly trastuzumab in HER2 overexpressing cancer and to assess the efficacy of afatinib given at the MTD dosage, with 3-weekly trastuzumab in HER2 overexpressing metastatic breast cancer. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Breast Neoplasms, Stomach Neoplasms
What is being tested?: Herceptin, afatinib and trastuzumab
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 3 sitesFrance
Study dates: 23 Jul 2012to 23 Jun 2016
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 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients aged 18 years and older
Patients with cancers overexpressing HER2 by Immunohistochemistry test( IHC) 3+ and/or IHC 2+ with positive gene amplification by FISH (confirmation on archived tissue needed)
Written informed consent that is consistent with ICH-GCP guidelines.
Patients must be eligible for treatment with trastuzumab.
Patients must have adequate organ function (kidney, liver, bone marrow, cardiac)
Eastern Cooperative Oncology Group (ECOG) = 0 or 1.
Measurable disease according to RECIST 1.1 (Phase Ib).

Who cannot join

Active brain metastases.
Prior treatment with erbB family targeting therapies within the past four weeks before start of therapy or concomitantly with the trial other than trastuzumab and/or lapatinib.
Patients having more than 2 lines of chemotherapy for the treatment of metastatic breast cancer (Phase Ib).

Trial locations and contacts

3 sites in 1 country.

France3 sites

CTR Georges-François Leclerc
Dijon, 21079
CTR René Gauducheau
Saint-Herblain, 44805
INS Claudius Regaud
Toulouse, 31059

Other trials in France

About this study

Official title: Phase I Trial of Afatinib in Combination With 3 Weekly Trastuzumab in Patients With Tumours Overexpressing HER2. Once the MTD of Afatinib With 3 Weekly Trastuzumab Was Established the Safety of This Dose Will be Assessed Also in Combination With Weekly Trastuzumab.

Conditions: Breast Neoplasms, Stomach Neoplasms
Being tested: Herceptin, afatinib, trastuzumab
Medical subject headings: Breast Neoplasms, Stomach Neoplasms

What participants receive

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

HerceptinDrug
3-weekly
afatinibDrug
at MTD level
trastuzumabDrug
3-weekly
HerceptinDrug
weekly
afatinibDrug
at MTD level
afatinibDrug
escalating dose

Study groups in NCT01649271
Study group	Role	What they receive
Phase Ia, group 1	Experimental	afatinib escalating dose with 3-weekly trastuzumab Receives: Drug: Herceptin; Drug: afatinib
Phase Ia, group 2	Experimental	afatinib at MTD dose with weekly trastuzumab Receives: Drug: afatinib; Drug: Herceptin
Phase Ib	Experimental	afatinib at MTD level with 3-weekly trastuzumab Receives: Drug: trastuzumab; Drug: afatinib

What is being measured

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

MTD of Afatinib in Combination With Trastuzumab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib).
Maximum Tolerated Dose (MTD) of Afatinib in combination with trastuzumab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD was defined as the highest dose studied at which the incidence of a DLT was less than 17% (i.e. 1/6 patients) during the first cycle.
One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.
Measured: First 21 days treatment cycle
Dose Limiting Toxicities During cycle1
Number of Patients With Dose Limiting Toxicity (DLT) occurring during Cycle 1 based on the investigator assessment.
One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.
Measured: First 21-day treatment cycle

Secondary outcomes (3)

Best Overall Response (BOR)
BOR represents the best response a patient had during their time in study from start of treatment until progression, the last evaluable assessment in absence of progression or start of subsequent anticancer therapy. For patients that died, BOR was to be calculated based on data up to last evaluable RECIST,v1.1 assessment prior to death. Death did not contribute as PD for BOR. As per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD. PD: At least a 20% increase in SLD of TL taking as reference the smallest SLD recorded since treatment started, together with an absolute increase in SLD of at least 5mm. SD: Neither sufficient shrinkage to qualify for PR, taking as reference the baseline SLD, nor sufficient increase to qualify for PD.
Measured: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until End of Treatment (EOT); up to 33 months
Objective Response
Objective Response (OR) was defined as best overall response of complete response (CR) or partial response (PR), where best overall response was determined according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 from first administration of study medication until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. As Per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD.
Measured: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 33 months
Clinical Benefit
Clinical benefit was defined as best overall response of CR or PR or stable disease (SD) where best overall response is defined according to RECIST version 1.1 from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.
As Per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD. SD: Neither sufficient shrinkage to qualify for PR, taking as reference the baseline SLD, nor sufficient increase to qualify for PD.
Measured: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 33 months

Timeline

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

23 Jul 201223 Jun 2016

First posted25 Jul 2012 (estimated)
Study start23 Jul 2012
Primary completion23 Jun 2016
Study completion23 Jun 2016

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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01649271
Sponsor's protocol ID: 1200.134
Other IDs: 2012-001753-10
Status last verified: Jan 2025
First submitted: 23 Jul 2012
Last updated: 11 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 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Trial of Afatinib in Combination With 3 Weekly Trastuzumab in Patients With Tumours Overexpressing HER2. Once the MTD of Afatinib With 3 Weekly Trastuzumab Was Established the Safety of This Dose Will be Assessed Also in Combination With Weekly Trastuzumab.
ClinicalTrials.gov ID: NCT01649271
Acronym / sponsor ID: 1200.134
Conditions: Breast Neoplasms, Stomach Neoplasms
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 23 Jul 2012 (actual)
Primary completion: 23 Jun 2016 (actual)
Study completion: 23 Jun 2016 (actual)
First posted: 25 Jul 2012 (estimated)
Results: Posted 6 Nov 2017

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Phase Ia, group 1	Experimental	Drug: Herceptin, Drug: afatinibafatinib escalating dose with 3-weekly trastuzumab
Phase Ia, group 2	Experimental	Drug: afatinib, Drug: Herceptinafatinib at MTD dose with weekly trastuzumab
Phase Ib	Experimental	Drug: trastuzumab, Drug: afatinibafatinib at MTD level with 3-weekly trastuzumab

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Patients aged 18 years and older
Patients with cancers overexpressing HER2 by Immunohistochemistry test( IHC) 3+ and/or IHC 2+ with positive gene amplification by FISH (confirmation on archived tissue needed)
Written informed consent that is consistent with ICH-GCP guidelines.
Patients must be eligible for treatment with trastuzumab.
Patients must have adequate organ function (kidney, liver, bone marrow, cardiac)

Key exclusion criteria (3 listed)

Active brain metastases.
Prior treatment with erbB family targeting therapies within the past four weeks before start of therapy or concomitantly with the trial other than trastuzumab and/or lapatinib.
Patients having more than 2 lines of chemotherapy for the treatment of metastatic breast cancer (Phase Ib).

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
Herceptin3-weekly	Drug	Phase Ia, group 1
afatinibat MTD level	Drug	Phase Ia, group 2
trastuzumab3-weekly	Drug	Phase Ib
Herceptinweekly	Drug	Phase Ia, group 2
afatinibat MTD level	Drug	Phase Ib
afatinibescalating dose	Drug	Phase Ia, group 1

Primary outcome

MTD of Afatinib in Combination With Trastuzumab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib).
Time frame: First 21 days treatment cycle
Maximum Tolerated Dose (MTD) of Afatinib in combination with trastuzumab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD was defined as the highest dose studied at which the incidence of a DLT was less than 17% (i.e. 1/6 patients) during the first cycle. One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.
Dose Limiting Toxicities During cycle1
Time frame: First 21-day treatment cycle
Number of Patients With Dose Limiting Toxicity (DLT) occurring during Cycle 1 based on the investigator assessment. One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.

3 secondary outcomes

Best Overall Response (BOR)
Time frame: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until End of Treatment (EOT); up to 33 months
Objective Response
Time frame: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 33 months
Clinical Benefit
Time frame: Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 33 months

Results and safety

Results posted to the registry on 6 Nov 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg	6	0
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg	7	0

Primary outcome: MTD of Afatinib in Combination With Trastuzumab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib).

Time frame: First 21 days treatment cycle. Number. Unit: mg

Measure	Phase Ia: Afatinib +Trastuzumab 8 mg/kg n = 12
Value	20

Population analysed: Treated set: This analysis set includes all patients who were documented to have taken at least one dose of study medication.

Primary outcome: Dose Limiting Toxicities During cycle1

Time frame: First 21-day treatment cycle. Count of participants. Unit: Participants

Measure	Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg n = 6	Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg n = 6
Value	1	2

Population analysed: Treated set

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose administration of the study medication to 28 days after last drug administration; up to 33 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg	4 of 6 (66.7%)	6 of 6 (100%)	Not reported
Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg	4 of 7 (57.1%)	7 of 7 (100%)	Not reported

Limitations and caveats (from the sponsor): Phase Ib was not started due to the discontinuation of afatinib development in HER2 overexpressing metastatic breast cancer and also the availability of other approved efficacious treatment options.Thus the results are not provided for Phase Ib.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 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

3 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 Herceptin, afatinib and trastuzumab in people with Breast Neoplasms and Stomach Neoplasms, run by Boehringer Ingelheim at 3 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 7 inclusion and 3 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 11 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 3 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 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 6 Nov 2017). 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?

MTD of Afatinib in Combination With Trastuzumab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib). (time frame: First 21 days treatment cycle). 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 NCT01649271.

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 11 Feb 2025.