Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005398

Trial Description

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Title

Randomized, Open-label, Phase II Study Comparing the Efficacy and the Safety of Cabazitaxel Versus Weekly Paclitaxel Given as Neo-adjuvant Treatment in Patients With Operable Triple Negative or Luminal B/HER2 Normal Breast Cancer (GENEVIEVE)

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Cabazitaxel is a new taxoid which promotes the tubulin assembly in vitro and stabilizes
microtubules against cold-induced depolymerization as efficiently as docetaxel and was
selected for development based on a better antiproliferative activity on resistant cell
lines than docetaxel. It has shown superior survival against mitoxantrone (MTX) plus
prednisone in docetaxel pre-treated hormone refractory metastatic prostate cancer patients
leading to registration of the compound. It showed a favorable toxicity profile with an
interestingly low rate of alopecia. In the Genevieve study it will be compared against
weekly paclitaxel which is currently most widely used treatment of breast cancer patients. A
head-to-head comparison in the neoadjuvant setting will allow a rapid and precise comparison
of efficacy and tolerability of cabacitaxel versus paclitaxel to decide in how far further
development of this taxoid in breast cancer is reasonable.

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Brief Summary in Scientific Language

Primary Objective To compare the pathologic complete response (pCR) rate in the breast
(ypT0/is ypN0/+) in patients with operable Triple Negative or luminal B/HER2 normal breast
cancer treated with either cabazitaxel or weekly paclitaxel.

Secondary Objective To assess

- pCR rates per arm separately for the stratified subpopulations.

- Objective response rate (ORR) in the breast according to WHO criteria.

- pCR rate defined as ypT0 ypN0.

- pCR rate defined as ypT0/is ypN0.

- pCR rate in the axillary lymph nodes (ypN0).

- 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.

- Breast conservation surgery rate.

- To assess the toxicity (NCI CTCAE V4.03) and compliance in both arms.

- Invasive loco-regional recurrence free survival (LRRFS), distant-disease-free survival
(DDFS), invasive disease-free survival (IDFS), and overall survival (OS).

- To explore the biomarkers and profiles potentially predicting response to treatment.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00005398
  •   2013/10/25
  •   2013/01/25
  •   yes
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Secondary IDs

  •   2012-003330-16 
  •   NCT01779479  (ClinicalTrials.gov)
  •   GBG 74  (German Breast Group)
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Health Condition or Problem studied

  •   Primary Breast Cancer
  •   C50 -  Malignant neoplasm of breast
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Interventions/Observational Groups

  •   Drug: Cabacitaxel
  •   Drug: Paclitaxel
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   II
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Primary Outcome

- pathologic complete response (pCR) rate; time frame: 15 months

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Secondary Outcome

- pathologic complete response (pCR) rate separately for subpopulations; time frame: 15 months; pathologic complete response (pCR) rate separately for stratified subpopulations
- Objective response rate (ORR); time frame: 15 months
- pCR rate defined as ypT0 ypN0; time frame: 15 months
- pCR rate defined as ypT0/is ypN0; time frame: 15 months
- pCR rate in the axillary lymph nodes (ypN0); time frame: 15 months
- pCR rate in patients with a clinical complete response (cCR); time frame: 15 months; To determine the pCR rate in patients with a clinical complete response (cCR) and a negative core biopsy before surgery
- local recurrence free survival (LRFS) in patients with a clinical complete response (cCR); time frame: 15 months; To determine the local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery
- Breast conservation surgery rate; time frame: 15 months
- Toxicity; time frame: 15 months; To assess the toxicity (NCI CTCAE V4.03) in both arms.
- Compliance; time frame: 15 months; To assess compliance in both arms.
- Invasive loco-regional recurrence free survival (LRRFS); time frame: 15 months
- Distant-disease-free survival (DDFS); time frame: 15 months
- Invasive disease-free survival (IDFS); time frame: 15 months
- Overall survival (OS); time frame: 15 months

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  •  
  • University Medical Center 
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Recruitment

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  •   2013/02/27
  •   326
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Female
  •   18   Years
  •   no maximum age
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Additional Inclusion 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.

- Patients must be in the following stages of disease: cT3 or cT2 or cT1c and cN+ or
cT1c and pNSLN+.

- In patients with multifocal or multicentric breast cancer, the largest lesion should
be evaluated.

- Centrally confirmed triple negative or luminal B/HER2-normal subtype. ER- and
PgR-negative defined as <1% stained cells. HER-2 negative defined as IHC 0+, 1+ or
IHC 2+ and FISH/SISH/CISH (ratio <2.0) negative. Luminal B defined as ER and/or PgR +
and > 14% Ki-67 stained cells. The formalin-fixed, paraffin-embedded (FFPE) breast
tissue block from the diagnostic core biopsy has therefore to be sent to the Dept. of
Pathology at the Charité, Berlin prior to randomization.

- Age >= 18 years.

- Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1 (see Appendix
A).

- Laboratory requirements: Hemoglobin > 9.0 g/dL, Absolute neutrophil count > 1.5 x
109/L, Platelet count > 100 x 109/L, AST/SGOT and/or ALT/SGPT < 2.5 x ULN; Total
bilirubin < 1.0 x ULN, Serum creatinine < 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN,
creatinine clearance will be calculated according to CKD-EPI formula and patients
with creatinine clearance < 60 mL/min should be excluded (see Appendix 2 for
formula).

- 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.

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Exclusion Criteria

- Any prior treatment for primary breast cancer including radiation therapy

- History of ipsi/ or contra-lateral invasive breast cancer

- Locally advanced disease including N3 and metastatic disease

- Patients in the following stages of disease are not allowed: cT4

- Prior malignancy without being disease-free for more than 5 years (except carcinoma
in situ of the cervix or other in situ cancer (e.g. bladder cancer) and adequately
treated basal cell carcinoma of the skin.

- Clinically significant (i.e. active) cardiovascular disease, including
cerebrovascular accident (≤6 months before enrolment), myocardial infarction,
arterial thrombotic events (≤6 months before enrolment), unstable angina pectoris,
New York Heart Association (NYHA) ≥ grade 2 congestive heart failure and/or
hypertension, serious cardiac arrhythmia requiring medication during the study and
that might interfere with regularity of the study treatment, or not controlled by
medication

- Any severe acute or chronic medical condition which could impair the ability of the
patient to participate to the study or to comply with the study procedures or
interfere with interpretation of study results (such as significant neurological or
psychiatric disorders including psychotic disorders, dementia or seizures).

- Active infection.

- Sex hormones. Prior treatment must be stopped before study entry.

- Inability and unwillingness to comply with study visits, treatment, testing, and to
comply with the protocol.

- Administration of any live virus vaccine within 8 weeks preceding study entry.

- Use of any investigational agent within 30 days of administration of the first dose
of study drug or concurrent treatment on another clinical trial

- Requirement for radiation therapy concurrent with study anticancer treatment.
Patients who require breast or chest wall radiation therapy after surgery are
eligible

- Pregnancy or breastfeeding women

- Patients with childbearing potential who do not agree to use accepted and effective
method of contraception (barrier methods, intrauterine contraceptive devices,
sterilization) during the study treatment period and following a period of 6 months
after the last study drug administration.

- History of hypersensitivity (grade ≥ 3) to polysorbate 80 or any study drugs or
excipients

- Concurrent or planned treatment with potent strong inhibitors or strong inducers of
cytochrome P450 3A4/5 (a two-week wash-out period is necessary for patients who are
already on these treatments) (see Appendix 3)

- Contraindications to the use of corticosteroid treatment

- Symptomatic peripheral neuropathy grade ≥ 2 (National Cancer Institute Common
Terminology Criteria [NCI CTCAE] v.4.03).

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Addresses

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    • German Breast Group
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    • Luisenkrankenhaus Düsseldorf
    • Gunter von Minckwitz, Prof. Dr. 
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    • Julia Kaiser, PhD 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   5
  •   2013/10/23
* This entry means the parameter is not applicable or has not been set.