Carcinoma, Ductal, BreastPhase 2NCT01891357
Phase II Trial to Validate Markers for a Response Evaluation of a Combined Therapy in Patients With HER2+ Breast Cancer
A Phase 2 study testing Biopsy before and after three weeks of study treatment, paclitaxel and lapatinib in people with Carcinoma, Ductal, Breast, run by Women's Cancer Study Group GmbH at 10 sites in Germany.
Trial summary
The Neo-PREDICT-HER2 Study is phase II trial to validate predictive markers for the response evaluation of a combined chemo-immunotherapy in patients with HER2-positive early breast cancer. The only treatment arm consists of Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Carcinoma, Ductal, Breast
- What is being tested?
- Biopsy before and after three weeks of study treatment, paclitaxel and lapatinib
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 10 sitesGermany
- Study dates
- 30 Sep 2013to 16 Nov 2016
- 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 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients, age at diagnosis 18 - 75 years
- Histological confirmed unilateral primary invasive carcinoma of the breast
- Clinical Stage Tumor 1 (cT1) (> 1 cm) - Clinical Stage Tumor 4 (cT4) (if operable, inflammatory breast cancer is excluded)
- HER2 over-expressing tumor confirmed by: 3+ by Immuno-histochemistry (IHC) and/or HER2/neu gene amplification by fluorescence, chromogenic or silver in-situ hybridization [Fluorescent In-Situ Hybridization (FISH), Chromogenic In-Situ Hybridization (CISH) or Silver In-Situ Hybridization (SISH); > 6 HER2 gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of ≥ 2.0]
- Clinically node positive disease or node negative disease
- No clinical evidence for distant metastasis (cM0) after conventional staging
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- Performance Status Eastern Cooperative Oncology Group (ECOG) ≤ 1 or Karnofsky Index (KI) ≥ 80%
- Baseline Left Ventricular Ejection Fraction (LVEF) > 50% measured by echocardiography
- Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients
- The patient must be accessible for treatment and follow-up
- Written informed consent including a written informed consent for shipping of tumor block for central pathology review and evaluation prior to the start of any study procedures
Who cannot join
- Known hypersensitivity reaction to the compounds or incorporated substances
- Known polyneuropathy grade ≥ 2
- Have acute or currently active or requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment).
- Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
- Prior or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
- Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
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- Male breast cancer
- Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
- Breast feeding women
- Sequential breast cancer
- Lack of patient compliance
- Inadequate organ function including:
- Leucocytes < 3.5 x 109/l
- Platelets < 100 x 109/l
- Absolute Neutrophil Count (ANC) < 1.5 x 109/l
- Hemoglobin < 9 g/dl
- Serum Creatinine > 1.5 mg/dl
- Serum Bilirubin > 1.1 mg/dl
- Alkaline phosphatase > 2.5 x Upper Limit of Normal (ULN)
- Aspartate Transaminase (ASAT) and/or Alanine Transaminase (ALAT) > 2.5 ULN
- Albumin < 2.5 g/dl
- Uncompensated cardiac function
- Malabsorption syndrome, disease significantly affecting gastrointestinal function
- Concomitant use of Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Germany10 sites
Praxis für gynäkologische Onkologie am Brustzentrum City
Berlin, 10713
Klinikum Chemnitz gGmbH
Chemnitz, Saxony, 09116
Krankenhaus Köln Holweide, Brustzentrum
Cologne, North Rhine-Westphalia, 51067
Klinikum Westfalen GmbH - Knappschaftskrankenhaus
Dortmund, North Rhine-Westphalia, 44309
Bethesda Krankenhaus, Senologie
Duisburg, North Rhine-Westphalia, 47053
Klinikum Esslingen
Esslingen am Neckar, Baden-Wurttemberg, 73730
Klinikum Frankfurt Höchst
Frankfurt am Main, Hesse, 65929
Niels-Stensen-Kliniken
Georgsmarienhütte, Lower Saxony, 49124
St. Barbara-KIinik
Hamm, North Rhine-Westphalia, 59073
SLK Kliniken
Heilbronn, Baden-Wurttemberg, 74078
About this study
Official title: A Multicenter Site, Open Label, Phase II Trial to Validate Predictive Markers for the Response Evaluation of a Combined Chemo-immunotherapy in Patients With HER2-positive Early Breast Cancer
The Neo-PREDICT-HER2 Study is phase II trial to validate predictive markers for the response evaluation of a combined chemo-immunotherapy in patients with HER2-positive early breast cancer. The only treatment arm consists of Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks.
Read the detailed description
Trastuzumab (T)-containing neoadjuvant chemotherapy has been reported to increase the probability of pathological complete response (pCR) in HER2 positive disease up to 67 %. Large trials revealed pCR rates (no remaining invasive and in situ components) of about 30-40 %, if anthracyclines/taxane based polychemotherapy was applied or about 40-45 % if no invasive tumor in the breast and lymph nodes was used as a pCR definition.
Nevertheless, resistance to trastuzumab remains one of the most important challenges in adjuvant and metastatic breast cancer therapy causing poor prognosis with an increased incidence of cerebral metastasis and limited therapeutic options after disease progression6. An improvement shows the combination of trastuzumab and lapatinib, which has been reported to have increased efficacy in in-vitro and in metastatic setting in patients who were mostly resistant to both therapies in the previous course of disease. Recent data from the neoadjuvant setting (neoALTTO) - on a paclitaxel backbone - showed a significantly higher pCR rate after L + T than with either compound separately (47 % vs. 20 % and 27.6 % respectively). Several trials are planned to evaluate the combination of both therapies in the adjuvant and neoadjuvant setting.
Clinical response measured by sequential evaluation of different proliferation markers (such as Ki-67) following a course of neoadjuvant chemotherapy has been demonstrated to correlate significantly with an increased risk of relapse in patients not achieving pathological complete response. It is therefore clinically relevant to evaluate such proliferation tools for early prediction of combination therapy efficacy (chemotherapy and HER2 targeted therapy). So far, it remains unclear which method of proliferation measurement is the optimal marker for response evaluation regarding a combined chemo-immunotherapy. However, measurement of proliferation and apoptosis genes as well as assessment of changes in Phosphatidylinositol 3-kinases (PI3K), Protein Kinase B (AKT), Insulin-like Growth Factor (IGF) and stem cell signalling after a short course of therapy could provide a unique signature for a dynamic response evaluation.
The planned trial will validate predictive markers and a dynamic model based on the sequential evaluation of different proliferation and apoptosis markers. Furthermore it will assess the pCR-rate after 12 weeks of therapy. The aim of the study is to define a predictive marker for the response evaluation of a combined chemo-immunotherapy.
- Conditions
- Carcinoma, Ductal, Breast
- Being tested
- Biopsy before and after three weeks of study treatment, paclitaxel, lapatinib, trastuzumab
- Keywords
- Unilateral primary invasive carcinoma of the breast
- Medical subject headings
- Carcinoma, Ductal, Breast
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy before and after three weeks of study treatmentProcedure or surgery
Core biopsies for histological analyses, to be analysed by the central pathology
paclitaxelDrug
lapatinibDrug
trastuzumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Paclitaxel + Lapatinib + Trastuzumab | Experimental | Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment Receives: Procedure: Biopsy before and after three weeks of study treatment; Drug: paclitaxel; Drug: lapatinib; Drug: trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR)
pCR was defined at the time of surgery and measured by size of residual tumor, proportion of vital cells within invasive carcinoma, number of positive lymph nodes (ypN) and size of the largest lymph node metastasis and ductal carcinoma in situ (ypT). pCR is defined as ypT0/is, ypN0. Further exploratory pCR definitions were ypT0, ypN0 (total pCR) and ypT0/is (near pCR).
Measured: Average of 16 weeks
Secondary outcomes (2)
Event Free Survival (EFS)
Measured: 5-year survival
Overall Survival (OS)
Measured: 5-year survival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2013 (estimated)
- Study start30 Sep 2013
- Primary completion16 Nov 2016
- Study completion16 Nov 2016
Why it stopped: Early termination due to significant lack of relevant patient data for evaluation of objectives.
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 Carcinoma, Ductal, BreastStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Women's Cancer Study Group GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Mathias Warm, MD, Principal investigator, Krankenhaus Köln Holweide
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01891357
- Sponsor's protocol ID
- WSG-AM07 (Neo-PREDICT-HER2)
- Other IDs
- 2012-003679-21
- Status last verified
- Sep 2019
- First submitted
- 14 May 2013
- Last updated
- 17 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Site, Open Label, Phase II Trial to Validate Predictive Markers for the Response Evaluation of a Combined Chemo-immunotherapy in Patients With HER2-positive Early Breast Cancer
- ClinicalTrials.gov ID
- NCT01891357
- Acronym / sponsor ID
- WSG-AM07 (Neo-PREDICT-HER2)
- Conditions
- Carcinoma, Ductal, Breast
- Keywords
- Unilateral primary invasive carcinoma of the breast
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early termination due to significant lack of relevant patient data for evaluation of objectives.
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Women's Cancer Study Group GmbHUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 30 Sep 2013 (actual)
- Primary completion
- 16 Nov 2016 (actual)
- Study completion
- 16 Nov 2016 (actual)
- First posted
- 3 Jul 2013 (estimated)
- Results
- Posted 17 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Neo-PREDICT-HER2 Study is phase II trial to validate predictive markers for the response evaluation of a combined chemo-immunotherapy in patients with HER2-positive early breast cancer. The only treatment arm consists of Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks.
Detailed description
Trastuzumab (T)-containing neoadjuvant chemotherapy has been reported to increase the probability of pathological complete response (pCR) in HER2 positive disease up to 67 %. Large trials revealed pCR rates (no remaining invasive and in situ components) of about 30-40 %, if anthracyclines/taxane based polychemotherapy was applied or about 40-45 % if no invasive tumor in the breast and lymph nodes was used as a pCR definition.
Nevertheless, resistance to trastuzumab remains one of the most important challenges in adjuvant and metastatic breast cancer therapy causing poor prognosis with an increased incidence of cerebral metastasis and limited therapeutic options after disease progression6. An improvement shows the combination of trastuzumab and lapatinib, which has been reported to have increased efficacy in in-vitro and in metastatic setting in patients who were mostly resistant to both therapies in the previous course of disease. Recent data from the neoadjuvant setting (neoALTTO) - on a paclitaxel backbone - showed a significantly higher pCR rate after L + T than with either compound separately (47 % vs. 20 % and 27.6 % respectively). Several trials are planned to evaluate the combination of both therapies in the adjuvant and neoadjuvant setting.
Clinical response measured by sequential evaluation of different proliferation markers (such as Ki-67) following a course of neoadjuvant chemotherapy has been demonstrated to correlate significantly with an increased risk of relapse in patients not achieving pathological complete response. It is therefore clinically relevant to evaluate such proliferation tools for early prediction of combination therapy efficacy (chemotherapy and HER2 targeted therapy). So far, it remains unclear which method of proliferation measurement is the optimal marker for response evaluation regarding a combined chemo-immunotherapy. However, measurement of proliferation and apoptosis genes as well as assessment of changes in Phosphatidylinositol 3-kinases (PI3K), Protein Kinase B (AKT), Insulin-like Growth Factor (IGF) and stem cell signalling after a short course of therapy could provide a unique signature for a dynamic response evaluation.
The planned trial will validate predictive markers and a dynamic model based on the sequential evaluation of different proliferation and apoptosis markers. Furthermore it will assess the pCR-rate after 12 weeks of therapy. The aim of the study is to define a predictive marker for the response evaluation of a combined chemo-immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Paclitaxel + Lapatinib + Trastuzumab | Experimental | Procedure: Biopsy before and after three weeks of study treatment, Drug: paclitaxel, Drug: lapatinib, Drug: trastuzumabPaclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Female patients, age at diagnosis 18 - 75 years
- Histological confirmed unilateral primary invasive carcinoma of the breast
- Clinical Stage Tumor 1 (cT1) (> 1 cm) - Clinical Stage Tumor 4 (cT4) (if operable, inflammatory breast cancer is excluded)
- HER2 over-expressing tumor confirmed by: 3+ by Immuno-histochemistry (IHC) and/or HER2/neu gene amplification by fluorescence, chromogenic or silver in-situ hybridization [Fluorescent In-Situ Hybridization (FISH), Chromogenic In-Situ Hybridization (CISH) or Silver In-Situ Hybridization (SISH); > 6 HER2 gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of ≥ 2.0]
- Clinically node positive disease or node negative disease
Key exclusion criteria (24 listed)
- Known hypersensitivity reaction to the compounds or incorporated substances
- Known polyneuropathy grade ≥ 2
- Have acute or currently active or requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment).
- Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
- Prior or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
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 |
|---|---|---|
| Biopsy before and after three weeks of study treatmentCore biopsies for histological analyses, to be analysed by the central pathology | Procedure or surgery | Paclitaxel + Lapatinib + Trastuzumab |
| paclitaxel | Drug | Paclitaxel + Lapatinib + Trastuzumab |
| lapatinib | Drug | Paclitaxel + Lapatinib + Trastuzumab |
| trastuzumab | Drug | Paclitaxel + Lapatinib + Trastuzumab |
Primary outcome
Pathological Complete Response (pCR)
Time frame: Average of 16 weeks
pCR was defined at the time of surgery and measured by size of residual tumor, proportion of vital cells within invasive carcinoma, number of positive lymph nodes (ypN) and size of the largest lymph node metastasis and ductal carcinoma in situ (ypT). pCR is defined as ypT0/is, ypN0. Further exploratory pCR definitions were ypT0, ypN0 (total pCR) and ypT0/is (near pCR).
2 secondary outcomes
Event Free Survival (EFS)
Time frame: 5-year survival
Overall Survival (OS)
Time frame: 5-year survival
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Mathias Warm, MD principal investigator
Krankenhaus Köln Holweide
10 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 Biopsy before and after three weeks of study treatment, paclitaxel and lapatinib in people with Carcinoma, Ductal, Breast, run by Women's Cancer Study Group GmbH at 10 sites in Germany.
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 11 inclusion and 24 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: stopped early, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany. 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 17 Sep 2019). 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?
Pathological Complete Response (pCR) (time frame: Average of 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Sep 2019.