Tubular Breast Cancer Stage IIPhase 3GeparSeptoNCT01583426
Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)
A Phase 3 study testing nab-Paclitaxel and Paclitaxel in people with Tubular Breast Cancer Stage II and Mucinous Breast Cancer Stage II, run by GBG Forschungs GmbH at 1 site in Germany.
Trial summary
Current guidelines as those from the AGO-Breast commission recommend for neoadjuvant breast cancer patients either a sequence of 4 cycles EC followed by 4 cycles of a taxane or 6 cycles of TAC based on previous large scale studies. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Tubular Breast Cancer Stage II, Mucinous Breast Cancer Stage II, Breast Cancer Female NOS
- What is being tested?
- nab-Paclitaxel and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,229 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2012to Dec 2018
- 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
- Patients will be eligible for study participation only if they comply with the following criteria:
- Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation must be sent to GBG Forschungs GmbH.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
- Tumor lesion in the breast with a palpable size of >= 2 cm or a sonographical size of >= 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 must be in the following stages of disease:
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- - cT2 - cT4a-d or
- cT1c and cN+ or
- - cT1c and pNSLN+ or
- - cT1c and ER-neg and PR-neg or
- - cT1c and Ki67 > 20%
- - cT1c and HER2-pos
- In patients with multifocal or multicentric breast cancer, the largest lesion should be measured.
- Centrally confirmed ER/PR/HER-2, Ki-67 and SPARC status detected on core biopsy. ER/PR positive is defined as >1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridisation (ISH) ratio >2.0. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization.
- Age >= 18 years.
- Karnofsky Performance status index >= 80%.
- Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results must be above the normal limit of the institution. For patients with HER2-positive tumors LVEF must be >= 55%.
- Laboratory requirements:
- Hematology
- - Absolute neutrophil count (ANC) >= 2.0 x 109 / L and
- Platelets >= 100 x 109 / L and
- Hemoglobin >= 10 g/dL (>= 6.2 mmol/L)
- Hepatic function
- - Total bilirubin < 1.5x UNL and
- ASAT (SGOT) and ALAT (SGPT) <= 1.5x UNL and
- Alkaline phosphatase <= 2.5x UNL.
- Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential.
- Complete staging work-up within 3 months prior to randomization. All patients must have bilateral mammography, breast ultrasound (<= 21 days), breast MRI (optional), chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scan done. In case of positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated.
- Patients must be available and compliant for central diagnostics, treatment and follow-up.
Who cannot join
- Prior chemotherapy for any malignancy.
- Prior radiation therapy for breast cancer.
- Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
- Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy).
- Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
- 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, uncontrolled or poorly controlled arterial hypertension (i.e. BP >160 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
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- History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
- Persons who have been admitted to an institution by order of jurisdictional or governmental grounds.
- Pre-existing motor or sensory neuropathy of grade 2 or more by NCI-CTC criteria v 4.0.
- Currently active infection.
- Definite contraindications for the use of corticosteroids.
- Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol.
- Concurrent treatment with:
- - chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (10 mg or less methylprednisolone or equivalent).
- - sex hormones. Prior treatment must be stopped before study entry.
- - other experimental drugs or any other anti-cancer therapy.
- Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry.
- Male patients.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Phase III Trial Comparing Nanoparticle-based Paclitaxel With Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Patients With Early Breast Cancer (GeparSepto)
Current guidelines as those from the AGO-Breast commission recommend for neoadjuvant breast cancer patients either a sequence of 4 cycles EC followed by 4 cycles of a taxane or 6 cycles of TAC based on previous large scale studies.
Treatment of patients with HER2-positive disease should include also simultaneous application of trastuzumab.
Read more
Solvent-based taxanes (paclitaxel, docetaxel) cause severe toxicities not only by the active agents itself but also by the solvents like cremophor. Nab-paclitaxel (Abraxane®) is a solvent-free formulation of paclitaxel encapsulated in albumin. It does not require premedication with corticosteroids or antihistamines to prevent the risk of solvent-mediated hypersensitivity reactions. This new formulation improves safety profile, allows higher dosing with shorter infusion duration, and produces higher tumor drug concentration.
As neoadjuvant treatment does not only allow to compare competing treatment approaches with a very high quality (homogenous treatment population, precise assessment of response by histological assessment), but also to identify predictive markers, this trial will compare weekly nab-paclitaxel with solvent-based paclitaxel at their currently optimal doses.
In case of HER2-positive tumor status patients receive Pertuzumab and Trastuzumab additionally.
Read the detailed description
Primary Objectives:
To compare the pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer
Secondary Objectives:
- To assess the pCR rates per arm separately for the stratified subpopulations.
- To determine the rates of ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0; and regression grades.
- To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in both arms.
- To assess clinical response rate after taxane in both groups
- To determine the breast conservation rate after each treatment.
- To assess the toxicity and compliance.
- To assess the time of onset of grade 3 neuropathy
- To assess the time of resolution of grade 3/4 neuropathy to at least grade 1
- To determine loco-regional invasive recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS) in both arms and according to stratified subpopulations.
- To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone.
- To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.
- To examine and compare pre-specified molecular markers such as SPARC, gp60, calveoline 1 and other markers potentially differentially predicting efficacy of nab-paclitaxel and solvent-based paclitaxel on core biopsies before, during and after chemotherapy.
Objectives of Substudies:
- To assess, characterize, and correlate circulating tumor cells and proteins with the effect of treatment (CTC Substudy).
- To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect (Pharmacogenetic substudy)
- To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged < 45 years.
- Conditions
- Tubular Breast Cancer Stage II, Mucinous Breast Cancer Stage II, Breast Cancer Female NOS, Invasive Ductal Breast Cancer, Tubular Breast Cancer Stage III, HER-2 Positive Breast Cancer
- Being tested
- nab-Paclitaxel, Paclitaxel
- Keywords
- GeparSepto, GBG 69, GBG, German Breast Group, neo-adjuvant, GBG Forschungs GmbH, Tubular breast cancer stage II, Mucinous breast cancer stage II, Invasive ductal breast cancer, Tubular breast cancer stage III, HER-2 positive breast cancer, Inflammatory breast cancer
- Medical subject headings
- Carcinoma, Ductal, Breast, Inflammatory Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nab-PaclitaxelDrug
Also called Abraxane
nab-Paclitaxel 125 mg/m² weekly for 12 weeks
PaclitaxelDrug
Paclitaxel 80 mg/m² weekly for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| nab-Paclitaxel | Experimental | nab-Paclitaxel (125 mg/m² weekly, infusion) is applicated for 12 weeks, followed by epirubicin and cyclophosphamide, applicated 4 cycles 3-weekly . In case of HER2-positive tumor patients receive tarstuzumab and pertuzumab 3-weekly during all cycles. Receives: Drug: nab-Paclitaxel |
| Paclitaxel | Active comparator | Paclitaxel (80 mg/m² weekly, infusion) is applicated for 12 weeks, followed by epirubicin and cyclophosphamide, applicated 4 cycles 3-weekly . In case of HER2-positive tumor patients receive tarstuzumab and pertuzumab 3-weekly during all cycles. Receives: Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer.
No microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast and axilla.
Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries.
The primary endpoint will be summarized as pathological complete remission rate for each treatment group.
Measured: 24 weeks (time window + 3 weeks)
Secondary outcomes (18)
Rates of ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0, and regression grade
Response (by physical examination, imaging response, breast conservation) will also be summarized as rates in each treatment group.
Measured: 24 weeks (time window + 3 weeks)
Clinical and imaging response
To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in both arms.
Measured: 24 weeks (time window + 3 weeks)
Tolerability and safety
Descriptive statistics for the 4 treatments (each taxane +/- anti-HER2-treatment) will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.
Measured: during treatment (24 weeks)
pCR rates per arm
To assess clinical response rate after taxane in both groups.
Measured: 24 weeks (time window + 3 weeks)
Breast conservation rate
To determine the breast conservation rate after each treatment.
Measured: 24 weeks (time window + 3 weeks)
Onset of grade 3 neuropathy
To assess the time of onset of grade 3 neuropathy.
Measured: 24 weeks (time window + 3 weeks)
Resolution of grade 3/4 neuropathy
To assess the time of resolution of grade 3/4 neuropathy to at least grade 1.
Measured: 24 weeks (time window + 3 weeks)
Regional recurrence free survival (RRFS) in patients with initial node-positive axilla
To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone.
Measured: until event occurs - no event for cured patients
pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy
To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.
Measured: 24 weeks (time frame + 3 weeks)
Examination and comparison of molecular markers
To examine and compare pre-specified molecular markers such as SPARC, gp60, calveoline 1 and other markers potentially differentially predicting efficacy of nab-paclitaxel and solvent-based paclitaxel on core biopsies before, during and after chemotherapy.
The aim is to identify potential predictive short and long term parameters.
Measured: Baseline, 12 weeks and 24 weeks (time frame + 3 weeks)
CTC Substudy
To assess, characterize, and correlate circulating tumor cells and proteins with the effect of treatment.
Measured: Baseline, 12 weeks and 24 weeks (time frame + 3 weeks)
Pharmacogenetic substudy
To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect.
Measured: Baseline
Ovarian substudy
To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged <45 years.
Measured: Baseline, 6 months, 12 months, 18 months, 24 months 30 months
Loco-regional invasive recurrence free survival (LRRFS) in both arms and according to stratified subpopulations.
LRRFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.
Measured: 5 years
Distant-disease-free survival (DDFS) in both arms and according to stratified subpopulations.
DDFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.
Measured: 5 years
Invasive disease-free survival (IDFS) in both arms and according to stratified subpopulations.
IDFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.
Measured: 5 years
Overall survival (OS) in both arms and according to stratified subpopulations.
OS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.
Measured: 5 years
Surgical substudy in patients with high probability for pCR
If it can be shown at an interim analysis that the positive predictive value for a pCR of a negative (>=3) core biopsies before surgery in patients with complete clinical response is >90%, these patients might opt for having no further breast surgery.
Measured: Baseline, after 4 cycles and before surgery (time frame + 3 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2012 (estimated)
- Study startJul 2012
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Tubular Breast Cancer Stage IIStudies 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
- 1,229 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation, Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Michael Untch, Prof MD, Principal investigator, AGO, ASCO, DKG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01583426
- Sponsor's protocol ID
- GBG 69
- Other IDs
- 2011-004714-41
- Acronym
- GeparSepto
- Status last verified
- Aug 2020
- First submitted
- 18 Apr 2012
- Last updated
- 6 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Loibl S, von Minckwitz G, Schneeweiss A, Paepke S, Lehmann A, Rezai M, Zahm DM, Sinn P, Khandan F, Eidtmann H, Dohnal K, Heinrichs C, Huober J, Pfitzner B, Fasching PA, Andre F, Lindner JL, Sotiriou C, Dykgers A, Guo S, Gade S, Nekljudova V, Loi S, Untch M, Denkert C. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol. 2014 Oct 10;32(29):3212-20. doi: 10.1200/JCO.2014.55.7876. Epub 2014 Sep 8.
PubMed 25199759Huober J, von Minckwitz G, Denkert C, Tesch H, Weiss E, Zahm DM, Belau A, Khandan F, Hauschild M, Thomssen C, Hogel B, Darb-Esfahani S, Mehta K, Loibl S. Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat. 2010 Nov;124(1):133-40. doi: 10.1007/s10549-010-1103-9. Epub 2010 Aug 10.
PubMed 20697801Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. doi: 10.1200/JCO.2008.18.5397. Epub 2009 May 26.
PubMed 19470941Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kummel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG); Arbeitsgemeinschaft Gynakologische Onkologie-Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):345-356. doi: 10.1016/S1470-2045(15)00542-2. Epub 2016 Feb 8.
PubMed 26869049Fasching PA, Szeto C, Denkert C, Benz S, Weber K, Spilman P, Budczies J, Schneeweiss A, Stickeler E, Schmatloch S, Jackisch C, Karn T, Sinn HP, Warm M, van Mackelenbergh M, Rabizadeh S, Schem C, Heinmoller E, Mueller V, Marme F, Soon-Shiong P, Nekljudova V, Untch M, Loibl S. Inferred Immune-Cell Activity Is an Independent Predictor of HER2-Negative Breast Cancer Prognosis and Response to Paclitaxel-Based Therapy in the GeparSepto Trial. Clin Cancer Res. 2023 Jul 5;29(13):2456-2465. doi: 10.1158/1078-0432.CCR-22-2213.
PubMed 37014668Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M, Wimberger P, Forberger A, Tesch H, Jackisch C, Schmatloch S, Reinisch M, Solomayer EF, Schmitt WD, Hanusch C, Fasching PA, Lubbe K, Solbach C, Huober J, Rhiem K, Marme F, Reimer T, Schmidt M, Sinn BV, Janni W, Stickeler E, Michel L, Stotzer O, Hahnen E, Furlanetto J, Seiler S, Nekljudova V, Untch M, Loibl S. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021 Aug;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6. Epub 2021 Jul 9.
PubMed 34252375Furlanetto J, Jackisch C, Untch M, Schneeweiss A, Schmatloch S, Aktas B, Denkert C, Wiebringhaus H, Kummel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Costa SD, Gerber B, Nekljudova V, Loibl S, von Minckwitz G. Efficacy and safety of nab-paclitaxel 125 mg/m2 and nab-paclitaxel 150 mg/m2 compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat. 2017 Jun;163(3):495-506. doi: 10.1007/s10549-017-4200-1. Epub 2017 Mar 17.
PubMed 28315068
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase III Trial Comparing Nanoparticle-based Paclitaxel With Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Patients With Early Breast Cancer (GeparSepto)
- ClinicalTrials.gov ID
- NCT01583426
- Acronym / sponsor ID
- GeparSepto / GBG 69
- Conditions
- Tubular Breast Cancer Stage II, Mucinous Breast Cancer Stage II, Breast Cancer Female NOS, Invasive Ductal Breast Cancer, Tubular Breast Cancer Stage III, HER-2 Positive Breast Cancer
- Keywords
- GeparSepto, GBG 69, GBG, German Breast Group, neo-adjuvant, GBG Forschungs GmbH, Tubular breast cancer stage II, Mucinous breast cancer stage II
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,229 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Collaborators
- Celgene Corporation, Roche Pharma AG
- Study start
- Jul 2012
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 24 Apr 2012 (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.
Current guidelines as those from the AGO-Breast commission recommend for neoadjuvant breast cancer patients either a sequence of 4 cycles EC followed by 4 cycles of a taxane or 6 cycles of TAC based on previous large scale studies.
Treatment of patients with HER2-positive disease should include also simultaneous application of trastuzumab.
Solvent-based taxanes (paclitaxel, docetaxel) cause severe toxicities not only by the active agents itself but also by the solvents like cremophor. Nab-paclitaxel (Abraxane®) is a solvent-free formulation of paclitaxel encapsulated in albumin. It does not require premedication with corticosteroids or antihistamines to prevent the risk of solvent-mediated hypersensitivity reactions. This new formulation improves safety profile, allows higher dosing with shorter infusion duration, and produces higher tumor drug concentration.
As neoadjuvant treatment does not only allow to compare competing treatment approaches with a very high quality (homogenous treatment population, precise assessment of response by histological assessment), but also to identify predictive markers, this trial will compare weekly nab-paclitaxel with solvent-based paclitaxel at their currently optimal doses.
In case of HER2-positive tumor status patients receive Pertuzumab and Trastuzumab additionally.
Detailed description
Primary Objectives:
To compare the pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer
Secondary Objectives:
- To assess the pCR rates per arm separately for the stratified subpopulations.
- To determine the rates of ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0; and regression grades.
- To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in both arms.
- To assess clinical response rate after taxane in both groups
- To determine the breast conservation rate after each treatment.
- To assess the toxicity and compliance.
- To assess the time of onset of grade 3 neuropathy
- To assess the time of resolution of grade 3/4 neuropathy to at least grade 1
- To determine loco-regional invasive recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS) in both arms and according to stratified subpopulations.
- To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone.
- To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.
- To examine and compare pre-specified molecular markers such as SPARC, gp60, calveoline 1 and other markers potentially differentially predicting efficacy of nab-paclitaxel and solvent-based paclitaxel on core biopsies before, during and after chemotherapy.
Objectives of Substudies:
- To assess, characterize, and correlate circulating tumor cells and proteins with the effect of treatment (CTC Substudy).
- To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect (Pharmacogenetic substudy)
- To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged < 45 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| nab-Paclitaxel | Experimental | Drug: nab-Paclitaxelnab-Paclitaxel (125 mg/m² weekly, infusion) is applicated for 12 weeks, followed by epirubicin and cyclophosphamide, applicated 4 cycles 3-weekly . In case of HER2-positive tumor patients receive tarstuzumab and pertuzumab 3-weekly during all cycles. |
| Paclitaxel | Active comparator | Drug: PaclitaxelPaclitaxel (80 mg/m² weekly, infusion) is applicated for 12 weeks, followed by epirubicin and cyclophosphamide, applicated 4 cycles 3-weekly . In case of HER2-positive tumor patients receive tarstuzumab and pertuzumab 3-weekly during all cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Patients will be eligible for study participation only if they comply with the following criteria:
- Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation must be sent to GBG Forschungs GmbH.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
- Tumor lesion in the breast with a palpable size of >= 2 cm or a sonographical size of >= 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.
Key exclusion criteria (18 listed)
- Prior chemotherapy for any malignancy.
- Prior radiation therapy for breast cancer.
- Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
- Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy).
- Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
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 |
|---|---|---|
| nab-PaclitaxelAlso: Abraxanenab-Paclitaxel 125 mg/m² weekly for 12 weeks | Drug | nab-Paclitaxel |
| PaclitaxelPaclitaxel 80 mg/m² weekly for 12 weeks | Drug | Paclitaxel |
Primary outcome
Pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer.
Time frame: 24 weeks (time window + 3 weeks)
No microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast and axilla. Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. The primary endpoint will be summarized as pathological complete remission rate for each treatment group.
18 secondary outcomes
Rates of ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0, and regression grade
Time frame: 24 weeks (time window + 3 weeks)
Clinical and imaging response
Time frame: 24 weeks (time window + 3 weeks)
Tolerability and safety
Time frame: during treatment (24 weeks)
pCR rates per arm
Time frame: 24 weeks (time window + 3 weeks)
Breast conservation rate
Time frame: 24 weeks (time window + 3 weeks)
Onset of grade 3 neuropathy
Time frame: 24 weeks (time window + 3 weeks)
Resolution of grade 3/4 neuropathy
Time frame: 24 weeks (time window + 3 weeks)
Regional recurrence free survival (RRFS) in patients with initial node-positive axilla
Time frame: until event occurs - no event for cured patients
pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy
Time frame: 24 weeks (time frame + 3 weeks)
Examination and comparison of molecular markers
Time frame: Baseline, 12 weeks and 24 weeks (time frame + 3 weeks)
CTC Substudy
Time frame: Baseline, 12 weeks and 24 weeks (time frame + 3 weeks)
Pharmacogenetic substudy
Time frame: Baseline
Ovarian substudy
Time frame: Baseline, 6 months, 12 months, 18 months, 24 months 30 months
Loco-regional invasive recurrence free survival (LRRFS) in both arms and according to stratified subpopulations.
Time frame: 5 years
Distant-disease-free survival (DDFS) in both arms and according to stratified subpopulations.
Time frame: 5 years
Invasive disease-free survival (IDFS) in both arms and according to stratified subpopulations.
Time frame: 5 years
Overall survival (OS) in both arms and according to stratified subpopulations.
Time frame: 5 years
Surgical substudy in patients with high probability for pCR
Time frame: Baseline, after 4 cycles and before surgery (time frame + 3 weeks)
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 6 Aug 2020.
- Background: PubMed 25199759Loibl S, von Minckwitz G, Schneeweiss A, Paepke S, Lehmann A, Rezai M, Zahm DM, Sinn P, Khandan F, Eidtmann H, Dohnal K, Heinrichs C, Huober J, Pfitzner B, Fasching PA, Andre F, Lindner JL, Sotiriou C, Dykgers A, Guo S, Gade S, Nekljudova V, Loi S, Untch M, Denkert C. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol. 2014 Oct 10;32(29):3212-20. doi: 10.1200/JCO.2014.55.7876. Epub 2014 Sep 8.
- Background: PubMed 20697801Huober J, von Minckwitz G, Denkert C, Tesch H, Weiss E, Zahm DM, Belau A, Khandan F, Hauschild M, Thomssen C, Hogel B, Darb-Esfahani S, Mehta K, Loibl S. Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat. 2010 Nov;124(1):133-40. doi: 10.1007/s10549-010-1103-9. Epub 2010 Aug 10.
- Background: PubMed 19470941Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. doi: 10.1200/JCO.2008.18.5397. Epub 2009 May 26.
- Results publication: PubMed 26869049Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kummel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG); Arbeitsgemeinschaft Gynakologische Onkologie-Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):345-356. doi: 10.1016/S1470-2045(15)00542-2. Epub 2016 Feb 8.
- Derived from this study: PubMed 37014668Fasching PA, Szeto C, Denkert C, Benz S, Weber K, Spilman P, Budczies J, Schneeweiss A, Stickeler E, Schmatloch S, Jackisch C, Karn T, Sinn HP, Warm M, van Mackelenbergh M, Rabizadeh S, Schem C, Heinmoller E, Mueller V, Marme F, Soon-Shiong P, Nekljudova V, Untch M, Loibl S. Inferred Immune-Cell Activity Is an Independent Predictor of HER2-Negative Breast Cancer Prognosis and Response to Paclitaxel-Based Therapy in the GeparSepto Trial. Clin Cancer Res. 2023 Jul 5;29(13):2456-2465. doi: 10.1158/1078-0432.CCR-22-2213.
- Derived from this study: PubMed 34252375Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M, Wimberger P, Forberger A, Tesch H, Jackisch C, Schmatloch S, Reinisch M, Solomayer EF, Schmitt WD, Hanusch C, Fasching PA, Lubbe K, Solbach C, Huober J, Rhiem K, Marme F, Reimer T, Schmidt M, Sinn BV, Janni W, Stickeler E, Michel L, Stotzer O, Hahnen E, Furlanetto J, Seiler S, Nekljudova V, Untch M, Loibl S. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021 Aug;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6. Epub 2021 Jul 9.
- Derived from this study: PubMed 28315068Furlanetto J, Jackisch C, Untch M, Schneeweiss A, Schmatloch S, Aktas B, Denkert C, Wiebringhaus H, Kummel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Costa SD, Gerber B, Nekljudova V, Loibl S, von Minckwitz G. Efficacy and safety of nab-paclitaxel 125 mg/m2 and nab-paclitaxel 150 mg/m2 compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat. 2017 Jun;163(3):495-506. doi: 10.1007/s10549-017-4200-1. Epub 2017 Mar 17.
- Sponsor study homepageLink 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.
Michael Untch, Prof MD principal investigator
AGO, ASCO, DKG
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 nab-Paclitaxel and Paclitaxel in people with Tubular Breast Cancer Stage II and Mucinous Breast Cancer Stage II, 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 29 inclusion and 18 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 6 Aug 2020. 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?
Pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer. (time frame: 24 weeks (time window + 3 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 NCT01583426, which also lists 7 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 6 Aug 2020.