Breast CancerPhase 3GeparQuintoNCT00567554
Bevacizumab, Everolimus (RAD001), and Lapatinib as Neoadjuvant Chemotherapy Regimes for Primary Breast Cancer
A Phase 3 study testing epirubicin - cyclophosphamide / docetaxel, epirubicin - cyclophosphamide / docetaxel + bevacizumab and paclitaxel in people with Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
Trial summary
Anthracycline-taxane based chemotherapy regimens are recommended mainly by current guidelines for neoadjuvant application of systemic treatment. The addition of other cytotoxic agents, e.g. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- epirubicin - cyclophosphamide / docetaxel, epirubicin - cyclophosphamide / docetaxel + bevacizumab and paclitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,600 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2007to Oct 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Written informed consent
- Complete baseline documentation sent to GBG Forschungs GmbH;
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is not allowed.
- Tumor lesion in the breast with a palpable size of ≥ 2 cm or a sonographically size of at least 1 cm in maximum diameter. The lesion has to be measurable in two-dimensions preferably by sonography. In case of inflammatory disease the extent of inflammation can be used as measurable lesion;
- Patients should have stages of disease in which adjuvant chemotherapy would be considered.
- Locally advanced tumors with cT4 or cT3 or
Show all 18Show fewer
- Estrogen (ER)- and progesterone (PgR)-receptor negative tumors or
- ER or PgR positive tumors which are cN+ (for cT2) or pNSLN+ (for cT1) * During the Run-In-Safety phase only patients with cT4 or cT3 cN+ disease are eligible.
- Known HER-2/neu status detected on core biopsy. HER-2/neu positive is defined as HercepTest IHC 3+ or FISH+;
- Age older than 18 years;
- Karnofsky Performance status index at least 80%;
- Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 1 month prior to registration.
- Laboratory requirements:
- Hematology: Absolute neutrophil count (ANC) ≥ 2.0 x 10e9/L platelets ≥ 100 x 10e9/L, Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L) Hepatic function: Total bilirubin < 1 x UNL ASAT (SGOT) and ALAT (SGPT)≤ 2.5 x UNL Alkaline phosphatase ≤ 5 UNL. Patients with ASAT and / or ALAT > 1.5 x UNL associated with alkaline phosphatase > 2.5 x UNL are not eligible for the study; Renal function: Creatinine ≤ 175 µmol/L (2 mg/dL) < 1,25 UNL (or the calculated creatinine clearance ≥ 60 mL/min) Urine dipstick for proteinuria < 2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis should undergo a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours
- Paraffin tumor tissue block and two serum samples centrally made available
- Negative pregnancy test (urine or serum)
- Complete staging work-up within 3 months prior to registration.
- Patients must be available and compliant for treatment and follow-up.
Who cannot join
- Patients with low or moderate risk, which are only doubtful candidates for adjuvant chemotherapy
- Evidence of distant metastasis;
- Prior chemotherapy for any malignancy;
- Prior radiation therapy for breast cancer;
- Pregnant or lactating patients.
- Inadequate general condition
Show all 22Show fewer
- Previous malignant disease
- Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease
- Previous thromboembolic event
- Known hemorrhagic diathesis or increased bleeding risk
- History of significant neurological or psychiatric disorders that would prohibit the understanding and giving of informed consent;
- Pre-existing motor or sensory neuropathy of a severity more than grade 2 by NCI criteria
- Currently active infection;incomplete wound healing
- Active peptic ulcer
- Disease significantly affecting gastrointestinal function
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrollment
- Severe pulmonary condition/illness
- Unstable diabetes mellitus; insulin dependent type II diabetes mellitus
- Major surgery or incomplete wound healing within the last 28 days
- Definite contraindications for the use of corticosteroids
- Known hypersensitivity reaction to one of the investigational compounds or incorporated substances; or known dihydropyrimidine dehydrogenase deficiency
- Concurrent treatment with:chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (20 mg methylprednisolone or equivalent); sex hormones.Virostatic agents like sorivudine or analogs like brivudine, concurrent treatment with aminoglycosides; anticoagulants: heparin, warfarin as well as acetic acid (e.g. Aspirin®) at a dose of > 325mg/day or clopidogrel at a dose of > 75 mg/day)e.other experimental drugs or any other anti-cancer therapy; drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (e.g. Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itraconazole, Ritonavir, Telithromycin, Erythromycin, Verapamil, Dilitazem, within the last 5 days or the expected need for these treatments during study participation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III Trials Program Exploring the Integration of Bevacizumab, Everolimus (RAD001), and Lapatinib Into Current Neoadjuvant Chemotherapy Regimes for Primary Breast Cancer
Anthracycline-taxane based chemotherapy regimens are recommended mainly by current guidelines for neoadjuvant application of systemic treatment. The addition of other cytotoxic agents, e.g. antimetabolites, vincaalkaloids, or platinum salts resulted in marginal increase in efficacy, but was associated also with an increase in toxicity. Recently, only the addition of the Her-2 antibody trastuzumab has significantly improved pathologic response rate.
Therefore, two major strategies are followed in current research projects:
Read more
- To improve the selection of patients according to their tumors' sensitivity to chemotherapy.
- To implement small molecules with specific mechanism of action.
Within the GeparQuinto trial, the first strategy is followed by:
- The PREDICT substudy. A gene signature specific for the response to anthracyclines and taxanes will be prospectively evaluated for its ability to identify patients with chance higher than 50% for a pCR. The results may leed to a better risk-benefit ratio for the use of conventional chemotherapy.
- Adapting further chemotherapy to the response of the tumor to the first couple of chemotherapy cycles. Based on the previous experience made by the GeparTrio study, patients not responding early have a low chance to respond with a pCR irrespective of the type of chemotherapy. So, if further chemotherapy is planned, therapy should be selected according to a favorable toxicity profile.
The second strategy is followed by investigating in three parallel group comparisons the efficiency of three distinct small molecules which appear to be generally active in breast cancer:
- Bevacizumab, an inhibitor of the VEGF pathway targeting tumor neo-angiogenesis.
- Lapatinib, an inhibitor of the Her-1 and Her-2 receptor tyrosine kinase.
- RAD001 (Everolimus), an inhibitor of the mTOR molecule, a central controller of tumor cell growth and angiogenesis and chemosensitizer.
Treatment for patients participating in the GeparQuinto study will be allocated according to the Her-2 status of the tumor as well as according to the sonographic response after the first 4 cycles of treatment. Experimental therapy with bevacizumab, lapatinib, and everolimus (RAD001) will be randomly added in distinct settings.
Read the detailed description
Primary objectives:
To compare the pCR rates of neoadjuvant treatment of epirubicin / cyclophosphamide followed by docetaxel (EC-T) with or without bevacizumab (EC-T vs. ECB-TB) in patients with Her-2 negative primary breast cancer (Setting I).
To compare the pCR rates of neoadjuvant treatment with weekly paclitaxel with or without Everolimus (RAD001) (Pw vs. PwR) in patients with Her-2 negative primary breast cancer showing no sonographic response to 4 cycles of EC +/-B (Setting II).
To compare the pCR rates of neoadjuvant treatment with epirubicin / cyclophosphamide followed by docetaxel with either trastuzumab or lapatinib (ECH-TH vs. ECL-TL) in patients with Her-2 positive primary breast cancer (Setting III).
Secondary objectives:
- To assess the toxicity of and compliance to all six treatments.
- To determine the response rates of the breast tumor and axillary nodes by physical examination and imaging tests (sonography, mammography, or MRI) after treatment in all arms.
- To determine the breast conservation rate after each treatment.
- To determine the (loco-regional and distant) disease-free and overall survival after each treatment. In Her-2 positive disease, the cerebral disease-free survival will be determined separately.
- To assess treatment efficacies in subgroups defined according to tumor stage (T2-3 vs. T4), receptor status (ER and / or PgR positive vs. ER and PgR negative) and response by best appropriate imaging method to the first four cycles of treatment (complete vs. partial vs. no change).
- To examine and compare pre-specified molecular markers such as Ki-67, phospho-mTOR, YB-1, COX-2, HuR, phospho-p70 S6K, p65 NF kappa B, PTEN, PI3-K, Akt, and a marker for stem cell like breast cancers (SOX-10) on core biopsy before and after end of chemotherapy.
Objectives of Substudies:
- To assess and correlate circulating tumor cells and proteins with the effect of treatment(CTC Substudy).
- To compare the pathologic complete response (pCR), breast conservation, clinical and imaging response rate (after four cycles and before surgery) in patients where the tumor shows a favorable profile of a predetermined combined biomarker set to those where the tumor does not show it (PREDICT Substudy).
- To determine the percentage of patients in which conventional axillary clearance can be substituted by sentinel node biopsy when a predetermined clinical algorithm is used (SENTINA Substudy).
- To assess the surgical outcome according to patient's and surgeon's perspectives in correlation with clinical and pathological response to systemic treatment (SOS - Surgical Outcome Substudy).
- To correlate Single Nucleotide Polymorphisms (SNPs) of genes which are either involved in the metabolism or in the effectiveness of the distinct therapies with the associated toxicity and histologically assessed treatment effect (Pharmacogenomic Substudy).
- Conditions
- Breast Cancer
- Being tested
- epirubicin - cyclophosphamide / docetaxel, epirubicin - cyclophosphamide / docetaxel + bevacizumab, paclitaxel, paclitaxel + everolimus (RAD001), epirubicin - cyclophosphamide / docetaxel + trastuzumab
- Keywords
- breast cancer, primary systemic therapy, pCR Rates, Bevacizumab, Trastuzumab, Lapatinib, Everolimus
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
epirubicin - cyclophosphamide / docetaxelDrug
epirubicin - cyclophosphamide / docetaxel + bevacizumabDrug
paclitaxelDrug
paclitaxel + everolimus (RAD001)Drug
epirubicin - cyclophosphamide / docetaxel + trastuzumabDrug
epirubicin - cyclophosphamide / docetaxel + lapatinibDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | EC-T Receives: Drug: epirubicin - cyclophosphamide / docetaxel |
| 2 | Experimental | EC-T +/- B Receives: Drug: epirubicin - cyclophosphamide / docetaxel + bevacizumab |
| 3 | Experimental | Pw Receives: Drug: paclitaxel |
| 4 | Experimental | Pw + RAD001 Receives: Drug: paclitaxel + everolimus (RAD001) |
| 5 | Experimental | EC-T + H Receives: Drug: epirubicin - cyclophosphamide / docetaxel + trastuzumab |
| 6 | Experimental | EC-T + L Receives: Drug: epirubicin - cyclophosphamide / docetaxel + lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the pCR rates of neoadjuvant treatment in all 3 Settings
Measured: 2009
Secondary outcomes (5)
To assess the toxicity of and compliance to all six treatments.
Measured: 2009
To determine the breast conservation rate after each treatment.
Measured: 2009
To determine the (loco-regional and distant) disease-free and overall survival after each treatment. In Her-2 positive disease the cerebral disease-free survival will be determined separately.
Measured: 2012
To assess treatment efficacies in subgroups defined according to tumor stage (T2-3 vs T4) receptor status (ER and/or PR pos. vs ER and PR neg.) and response by best appropriate imaging method to the first 4 cycles of treatment (complete vs partial vs no)
Measured: 2009
To examine and compare prespecified molecular markers on core biopsy before and after end of chemotherapy
Measured: 2012
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2007 (estimated)
- Study startOct 2007
- Primary completionAug 2011
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,600 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- AGO Study Group
- Responsible party
- Sponsor
- Investigators
- Gunter von Minckwitz, MD, Prof., Principal investigator, GBG Forschungs GmbHMichael Untch, MD, Prof., Study chair, AGO Study Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00567554
- Sponsor's protocol ID
- GBG 44
- Other IDs
- 2006-005834-19
- Acronym
- GeparQuinto
- Status last verified
- Feb 2016
- First submitted
- 4 Dec 2007
- Last updated
- 10 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fasching PA, Loibl S, Hu C, Hart SN, Shimelis H, Moore R, Schem C, Tesch H, Untch M, Hilfrich J, Rezai M, Gerber B, Costa SD, Blohmer JU, Fehm T, Huober J, Liedtke C, Weinshilboum RM, Wang L, Ingle JN, Muller V, Nekljudova V, Weber KE, Rack B, Rubner M, von Minckwitz G, Couch FJ. BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study. J Clin Oncol. 2018 Aug 1;36(22):2281-2287. doi: 10.1200/JCO.2017.77.2285. Epub 2018 May 23.
PubMed 29791287Untch M, von Minckwitz G, Gerber B, Schem C, Rezai M, Fasching PA, Tesch H, Eggemann H, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Loibl S; GBG and the AGO-B Study Group. Survival Analysis After Neoadjuvant Chemotherapy With Trastuzumab or Lapatinib in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the GeparQuinto (G5) Study (GBG 44). J Clin Oncol. 2018 May 1;36(13):1308-1316. doi: 10.1200/JCO.2017.75.9175. Epub 2018 Mar 15.
PubMed 29543566von Minckwitz G, Loibl S, Untch M, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Gerber B; GBG/AGO-B study groups; Gnauert K, Heinrich B, Pratz T, Groh U, Tanzer H, Villena C, Tulusan A, Liedtke B, Blohmer JU, Kittel K, Mau C, Potenberg J, Schilling J, Just M, Weiss E, Buckner U, Wolfgarten M, Lorenz R, Doering G, Feidicker S, Krabisch P, Deichert U, Augustin D, Kunz G, Kast K, von Minckwitz G, Nestle-Kramling C, Rezai M, Hoss C, Terhaag J, Fasching P, Staib P, Aktas B, Kuhn T, Khandan F, Mobus V, Solbach C, Tesch H, Stickeler E, Heinrich G, Wagner H, Abdallah A, Dewitz T, Emons G, Belau A, Rethwisch V, Lantzsch T, Thomssen C, Mattner U, Nugent A, Muller V, Noesselt T, Holms F, Muller T, Deuker JU, Schrader I, Strumberg D, Uleer C, Solomayer E, Runnebaum I, Link H, Tome O, Ulmer HU, Conrad B, Feisel-Schwickardi G, Eidtmann H, Schumacher C, Steinmetz T, Bauerfeind I, Kremers S, Langanke D, Kullmer U, Ober A, Fischer D, Kohls A, Weikel W, Bischoff J, Freese K, Schmidt M, Wiest W, Sutterlin M, Dietrich M, Griesshammer M, Burgmann DM, Hanusch C, Rack B, Salat C, Sattler D, Tio J, von Abel E, Christensen B, Burkamp U, Kohne CH, Meinerz W, Grasshoff ST, Decker T, Overkamp F, Thalmann I, Sallmann A, Beck T, Reimer T, Bartzke G, Deryal M, Weigel M, Huober J, Weder P, Steffens CC, Lemster S, Stefek A, Ruhland F, Hofmann M, Schuster J, Simon W, Kronawitter U, Clemens M, Fehm T, Janni W, Latos K, Bauer W, Rossmann A, Bauer L, Lampe D, Heyl V, Hoffmann G, Lorenz-Salehi F, Hackmann J, Schlag R. Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)dagger. Ann Oncol. 2014 Dec;25(12):2363-2372. doi: 10.1093/annonc/mdu455. Epub 2014 Sep 15.
PubMed 25223482von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Muller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynakologische Onkologie-Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. doi: 10.1056/NEJMoa1111065.
PubMed 22276820Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching PA, Kreienberg R, Tesch H, Hanusch C, Gerber B, Rezai M, Jackisch C, Huober J, Kuhn T, Nekljudova V, von Minckwitz G; German Breast Group (GBG); Arbeitsgemeinschaft Gynakologische Onkologie-Breast (AGO-B) Study Group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012 Feb;13(2):135-44. doi: 10.1016/S1470-2045(11)70397-7. Epub 2012 Jan 17.
PubMed 22257523
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Trials Program Exploring the Integration of Bevacizumab, Everolimus (RAD001), and Lapatinib Into Current Neoadjuvant Chemotherapy Regimes for Primary Breast Cancer
- ClinicalTrials.gov ID
- NCT00567554
- Acronym / sponsor ID
- GeparQuinto / GBG 44
- Conditions
- Breast Cancer
- Keywords
- breast cancer, primary systemic therapy, pCR Rates, Bevacizumab, Trastuzumab, Lapatinib, Everolimus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,600 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Collaborators
- AGO Study Group
- Study start
- Oct 2007
- Primary completion
- Aug 2011 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 5 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Anthracycline-taxane based chemotherapy regimens are recommended mainly by current guidelines for neoadjuvant application of systemic treatment. The addition of other cytotoxic agents, e.g. antimetabolites, vincaalkaloids, or platinum salts resulted in marginal increase in efficacy, but was associated also with an increase in toxicity. Recently, only the addition of the Her-2 antibody trastuzumab has significantly improved pathologic response rate.
Therefore, two major strategies are followed in current research projects:
- To improve the selection of patients according to their tumors' sensitivity to chemotherapy.
- To implement small molecules with specific mechanism of action.
Within the GeparQuinto trial, the first strategy is followed by:
- The PREDICT substudy. A gene signature specific for the response to anthracyclines and taxanes will be prospectively evaluated for its ability to identify patients with chance higher than 50% for a pCR. The results may leed to a better risk-benefit ratio for the use of conventional chemotherapy.
- Adapting further chemotherapy to the response of the tumor to the first couple of chemotherapy cycles. Based on the previous experience made by the GeparTrio study, patients not responding early have a low chance to respond with a pCR irrespective of the type of chemotherapy. So, if further chemotherapy is planned, therapy should be selected according to a favorable toxicity profile.
The second strategy is followed by investigating in three parallel group comparisons the efficiency of three distinct small molecules which appear to be generally active in breast cancer:
- Bevacizumab, an inhibitor of the VEGF pathway targeting tumor neo-angiogenesis.
- Lapatinib, an inhibitor of the Her-1 and Her-2 receptor tyrosine kinase.
- RAD001 (Everolimus), an inhibitor of the mTOR molecule, a central controller of tumor cell growth and angiogenesis and chemosensitizer.
Treatment for patients participating in the GeparQuinto study will be allocated according to the Her-2 status of the tumor as well as according to the sonographic response after the first 4 cycles of treatment. Experimental therapy with bevacizumab, lapatinib, and everolimus (RAD001) will be randomly added in distinct settings.
Detailed description
Primary objectives:
To compare the pCR rates of neoadjuvant treatment of epirubicin / cyclophosphamide followed by docetaxel (EC-T) with or without bevacizumab (EC-T vs. ECB-TB) in patients with Her-2 negative primary breast cancer (Setting I).
To compare the pCR rates of neoadjuvant treatment with weekly paclitaxel with or without Everolimus (RAD001) (Pw vs. PwR) in patients with Her-2 negative primary breast cancer showing no sonographic response to 4 cycles of EC +/-B (Setting II).
To compare the pCR rates of neoadjuvant treatment with epirubicin / cyclophosphamide followed by docetaxel with either trastuzumab or lapatinib (ECH-TH vs. ECL-TL) in patients with Her-2 positive primary breast cancer (Setting III).
Secondary objectives:
- To assess the toxicity of and compliance to all six treatments.
- To determine the response rates of the breast tumor and axillary nodes by physical examination and imaging tests (sonography, mammography, or MRI) after treatment in all arms.
- To determine the breast conservation rate after each treatment.
- To determine the (loco-regional and distant) disease-free and overall survival after each treatment. In Her-2 positive disease, the cerebral disease-free survival will be determined separately.
- To assess treatment efficacies in subgroups defined according to tumor stage (T2-3 vs. T4), receptor status (ER and / or PgR positive vs. ER and PgR negative) and response by best appropriate imaging method to the first four cycles of treatment (complete vs. partial vs. no change).
- To examine and compare pre-specified molecular markers such as Ki-67, phospho-mTOR, YB-1, COX-2, HuR, phospho-p70 S6K, p65 NF kappa B, PTEN, PI3-K, Akt, and a marker for stem cell like breast cancers (SOX-10) on core biopsy before and after end of chemotherapy.
Objectives of Substudies:
- To assess and correlate circulating tumor cells and proteins with the effect of treatment(CTC Substudy).
- To compare the pathologic complete response (pCR), breast conservation, clinical and imaging response rate (after four cycles and before surgery) in patients where the tumor shows a favorable profile of a predetermined combined biomarker set to those where the tumor does not show it (PREDICT Substudy).
- To determine the percentage of patients in which conventional axillary clearance can be substituted by sentinel node biopsy when a predetermined clinical algorithm is used (SENTINA Substudy).
- To assess the surgical outcome according to patient's and surgeon's perspectives in correlation with clinical and pathological response to systemic treatment (SOS - Surgical Outcome Substudy).
- To correlate Single Nucleotide Polymorphisms (SNPs) of genes which are either involved in the metabolism or in the effectiveness of the distinct therapies with the associated toxicity and histologically assessed treatment effect (Pharmacogenomic Substudy).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: epirubicin - cyclophosphamide / docetaxelEC-T |
| 2 | Experimental | Drug: epirubicin - cyclophosphamide / docetaxel + bevacizumabEC-T +/- B |
| 3 | Experimental | Drug: paclitaxelPw |
| 4 | Experimental | Drug: paclitaxel + everolimus (RAD001)Pw + RAD001 |
| 5 | Experimental | Drug: epirubicin - cyclophosphamide / docetaxel + trastuzumabEC-T + H |
| 6 | Experimental | Drug: epirubicin - cyclophosphamide / docetaxel + lapatinibEC-T + L |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Written informed consent
- Complete baseline documentation sent to GBG Forschungs GmbH;
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is not allowed.
- Tumor lesion in the breast with a palpable size of ≥ 2 cm or a sonographically size of at least 1 cm in maximum diameter. The lesion has to be measurable in two-dimensions preferably by sonography. In case of inflammatory disease the extent of inflammation can be used as measurable lesion;
- Patients should have stages of disease in which adjuvant chemotherapy would be considered.
Key exclusion criteria (22 listed)
- Patients with low or moderate risk, which are only doubtful candidates for adjuvant chemotherapy
- Evidence of distant metastasis;
- Prior chemotherapy for any malignancy;
- Prior radiation therapy for breast cancer;
- Pregnant or lactating patients.
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 |
|---|---|---|
| epirubicin - cyclophosphamide / docetaxel | Drug | 1 |
| epirubicin - cyclophosphamide / docetaxel + bevacizumab | Drug | 2 |
| paclitaxel | Drug | 3 |
| paclitaxel + everolimus (RAD001) | Drug | 4 |
| epirubicin - cyclophosphamide / docetaxel + trastuzumab | Drug | 5 |
| epirubicin - cyclophosphamide / docetaxel + lapatinib | Drug | 6 |
Primary outcome
To compare the pCR rates of neoadjuvant treatment in all 3 Settings
Time frame: 2009
5 secondary outcomes
To assess the toxicity of and compliance to all six treatments.
Time frame: 2009
To determine the breast conservation rate after each treatment.
Time frame: 2009
To determine the (loco-regional and distant) disease-free and overall survival after each treatment. In Her-2 positive disease the cerebral disease-free survival will be determined separately.
Time frame: 2012
To assess treatment efficacies in subgroups defined according to tumor stage (T2-3 vs T4) receptor status (ER and/or PR pos. vs ER and PR neg.) and response by best appropriate imaging method to the first 4 cycles of treatment (complete vs partial vs no)
Time frame: 2009
To examine and compare prespecified molecular markers on core biopsy before and after end of chemotherapy
Time frame: 2012
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2016.
- Derived from this study: PubMed 29791287Fasching PA, Loibl S, Hu C, Hart SN, Shimelis H, Moore R, Schem C, Tesch H, Untch M, Hilfrich J, Rezai M, Gerber B, Costa SD, Blohmer JU, Fehm T, Huober J, Liedtke C, Weinshilboum RM, Wang L, Ingle JN, Muller V, Nekljudova V, Weber KE, Rack B, Rubner M, von Minckwitz G, Couch FJ. BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study. J Clin Oncol. 2018 Aug 1;36(22):2281-2287. doi: 10.1200/JCO.2017.77.2285. Epub 2018 May 23.
- Derived from this study: PubMed 29543566Untch M, von Minckwitz G, Gerber B, Schem C, Rezai M, Fasching PA, Tesch H, Eggemann H, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Loibl S; GBG and the AGO-B Study Group. Survival Analysis After Neoadjuvant Chemotherapy With Trastuzumab or Lapatinib in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the GeparQuinto (G5) Study (GBG 44). J Clin Oncol. 2018 May 1;36(13):1308-1316. doi: 10.1200/JCO.2017.75.9175. Epub 2018 Mar 15.
- Derived from this study: PubMed 25223482von Minckwitz G, Loibl S, Untch M, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Gerber B; GBG/AGO-B study groups; Gnauert K, Heinrich B, Pratz T, Groh U, Tanzer H, Villena C, Tulusan A, Liedtke B, Blohmer JU, Kittel K, Mau C, Potenberg J, Schilling J, Just M, Weiss E, Buckner U, Wolfgarten M, Lorenz R, Doering G, Feidicker S, Krabisch P, Deichert U, Augustin D, Kunz G, Kast K, von Minckwitz G, Nestle-Kramling C, Rezai M, Hoss C, Terhaag J, Fasching P, Staib P, Aktas B, Kuhn T, Khandan F, Mobus V, Solbach C, Tesch H, Stickeler E, Heinrich G, Wagner H, Abdallah A, Dewitz T, Emons G, Belau A, Rethwisch V, Lantzsch T, Thomssen C, Mattner U, Nugent A, Muller V, Noesselt T, Holms F, Muller T, Deuker JU, Schrader I, Strumberg D, Uleer C, Solomayer E, Runnebaum I, Link H, Tome O, Ulmer HU, Conrad B, Feisel-Schwickardi G, Eidtmann H, Schumacher C, Steinmetz T, Bauerfeind I, Kremers S, Langanke D, Kullmer U, Ober A, Fischer D, Kohls A, Weikel W, Bischoff J, Freese K, Schmidt M, Wiest W, Sutterlin M, Dietrich M, Griesshammer M, Burgmann DM, Hanusch C, Rack B, Salat C, Sattler D, Tio J, von Abel E, Christensen B, Burkamp U, Kohne CH, Meinerz W, Grasshoff ST, Decker T, Overkamp F, Thalmann I, Sallmann A, Beck T, Reimer T, Bartzke G, Deryal M, Weigel M, Huober J, Weder P, Steffens CC, Lemster S, Stefek A, Ruhland F, Hofmann M, Schuster J, Simon W, Kronawitter U, Clemens M, Fehm T, Janni W, Latos K, Bauer W, Rossmann A, Bauer L, Lampe D, Heyl V, Hoffmann G, Lorenz-Salehi F, Hackmann J, Schlag R. Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)dagger. Ann Oncol. 2014 Dec;25(12):2363-2372. doi: 10.1093/annonc/mdu455. Epub 2014 Sep 15.
- Derived from this study: PubMed 22276820von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Muller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynakologische Onkologie-Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. doi: 10.1056/NEJMoa1111065.
- Derived from this study: PubMed 22257523Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching PA, Kreienberg R, Tesch H, Hanusch C, Gerber B, Rezai M, Jackisch C, Huober J, Kuhn T, Nekljudova V, von Minckwitz G; German Breast Group (GBG); Arbeitsgemeinschaft Gynakologische Onkologie-Breast (AGO-B) Study Group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012 Feb;13(2):135-44. doi: 10.1016/S1470-2045(11)70397-7. Epub 2012 Jan 17.
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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.
Gunter von Minckwitz, MD, Prof. principal investigator
GBG Forschungs GmbH
Michael Untch, MD, Prof. study chair
AGO Study Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing epirubicin - cyclophosphamide / docetaxel, epirubicin - cyclophosphamide / docetaxel + bevacizumab and paclitaxel in people with Breast Cancer, run by GBG Forschungs GmbH at 1 site 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 18 inclusion and 22 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 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To compare the pCR rates of neoadjuvant treatment in all 3 Settings (time frame: 2009). 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 NCT00567554, which also lists 5 linked publications.
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 2016.