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Primary Breast CancerPhase 2NCT01779479

Efficacy and Safety of Cabazitaxel Versus Weekly Paclitaxel as Neo-adjuvant Treatment in Patients With Triple Negative or Luminal B/HER2 Normal BC (GENEVIEVE)

A Phase 2 study testing Cabacitaxel and Paclitaxel in people with Primary Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Primary Breast Cancer
What is being tested?
Cabacitaxel and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
333 participants
Where
1 siteGermany
Study dates
Feb 2013to Feb 2016
Phase
Phase 2
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 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.
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  • 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.

Who cannot join

  • 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
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  • 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).

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Luisenkrankenhaus

    Düsseldorf, 40235

Other trials in Germany

About this study

Official 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)

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.

Read the detailed description

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.
Being tested
Cabacitaxel, Paclitaxel
Keywords
German Breast Group, GBG Forschungs GmbH, GBG, GBG 74, Genevieve, Breast Cancer, Primary Breast Cancer, Cabazitaxel, Paclitaxel, neo-adjuvant, triple negative, luminal B
Medical subject headings
Breast Neoplasms

What participants receive

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

  • CabacitaxelDrug

    Cabazitaxel 25 mg/m² i.v. (Day 1) every 3 weeks (cycle) as 1-hour i.v infusion for a total of up to 4 cycles over a maximum total treatment period of 15 weeks before surgery

  • PaclitaxelDrug

    Paclitaxel 80 mg/m² as 1-hour i.v infusion. Patients will receive weekly (Days 1, 8, 15) paclitaxel administrations for a maximum of 12 infusions for a maximum of 4 cycles over a maximum total treatment period of 15 weeks before surgery (1 cycle = 3 weeks).

Study groups in NCT01779479
Study groupRoleWhat they receive
CabacitaxelExperimentalNot described
Receives: Drug: Cabacitaxel
PaclitaxelActive comparatorNot described
Receives: Drug: Paclitaxel

What is being measured

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

  1. pathologic complete response (pCR) rate

    Measured: 15 months

Secondary outcomes (14)

  1. pathologic complete response (pCR) rate separately for subpopulations

    pathologic complete response (pCR) rate separately for stratified subpopulations

    Measured: 15 months

  2. Objective response rate (ORR)

    Measured: 15 months

  3. pCR rate defined as ypT0 ypN0

    Measured: 15 months

  4. pCR rate defined as ypT0/is ypN0

    Measured: 15 months

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

    Measured: 15 months

  6. pCR rate in patients with a clinical complete response (cCR)

    To determine the pCR rate in patients with a clinical complete response (cCR) and a negative core biopsy before surgery

    Measured: 15 months

  7. local recurrence free survival (LRFS) in patients with a clinical complete response (cCR)

    To determine the local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery

    Measured: 15 months

  8. Breast conservation surgery rate

    Measured: 15 months

  9. Toxicity

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

    Measured: 15 months

  10. Compliance

    To assess compliance in both arms.

    Measured: 15 months

  11. Invasive loco-regional recurrence free survival (LRRFS)

    Measured: 15 months

  12. Distant-disease-free survival (DDFS)

    Measured: 15 months

  13. Invasive disease-free survival (IDFS)

    Measured: 15 months

  14. Overall survival (OS)

    Measured: 15 months

Timeline

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

  1. First posted30 Jan 2013 (estimated)
  2. Study startFeb 2013
  3. Primary completionAug 2015
  4. Study completionFeb 2016

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
333 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01779479
Sponsor's protocol ID
GBG 74
Other IDs
2012-003330-16
Status last verified
Feb 2016
First submitted
25 Jan 2013
Last updated
1 Aug 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Kummel S, Paepke S, Huober J, Schem C, Untch M, Blohmer JU, Eiermann W, Gerber B, Hanusch C, Hilfrich J, Jackisch C, Schneeweiss A, Denkert C, Engels K, Klare P, Fasching PA, von Minckwitz G, Burchardi N, Loibl S. Randomised, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE). Eur J Cancer. 2017 Oct;84:1-8. doi: 10.1016/j.ejca.2017.06.037. Epub 2017 Jul 30.

    PubMed 28768217

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabacitaxel and Paclitaxel in people with Primary 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 13 inclusion and 19 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 1 Aug 2017. 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 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?

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?

pathologic complete response (pCR) rate (time frame: 15 months). 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 NCT01779479, which also lists 1 linked publication.

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 1 Aug 2017.

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