Bevacizumab, Everolimus (RAD001), and Lapatinib as Neoadjuvant Chemotherapy Regimes for Primary Breast Cancer

Sponsor
GBG Forschungs GmbH
Study ID
NCT00567554
Phase
PHASE3
Status
Completed

Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • epirubicin - cyclophosphamide / docetaxel — DRUG
  • epirubicin - cyclophosphamide / docetaxel + bevacizumab — DRUG
  • paclitaxel — DRUG
  • paclitaxel + everolimus (RAD001) — DRUG
  • epirubicin - cyclophosphamide / docetaxel + trastuzumab — DRUG
  • epirubicin - cyclophosphamide / docetaxel + lapatinib — DRUG

Study Details

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.

Key Dates

Start date
Oct 31, 2007
Status verified
Feb 2016
Primary completion
Aug 31, 2011
Completion
Oct 31, 2015

Study Design

Enrollment
2,600 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 1
    EC-T
  • Experimental: 2
    EC-T +/- B
  • Experimental: 3
    Pw
  • Experimental: 4
    Pw + RAD001
  • Experimental: 5
    EC-T + H
  • Experimental: 6
    EC-T + L

Primary Outcome Measure

To compare the pCR rates of neoadjuvant treatment in all 3 Settings [ Time Frame: 2009 ]

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