Docetaxel, Doxorubicin and Cyclophosphamide Versus Vinorelbine and Capecitabine in Patients Not Sufficiently / Sufficiently Responding as Preoperative Treatment of Locally Advanced or Operable Primary Breast Cancer

NCT00544765 | Completed Phase 3 DMC

• 1 other identifier: GBG 24
• Study Type: interventional
• Target: 2,014
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary objective of the study in patients without a sufficient sonographic response (i.e. iNC) to 2 cycles of TAC as preoperative treatment of operable (T\>/= 2cm, N0-2,M0) primary breast cancer: To determine the response rate determined by sonography (iRR = iCR+iPR) of further 4 cycles of docetaxel, doxorubicin and cyclophosphamide (TAC) and of 4 cycles of vinorelbine and capecitabine (NX) (TAC vs. NX) Primary objective of the study in patients with a sufficient sonographic response (i.e. iRR = iPR or iCR) to the first 2 cycles of TAC as preoperative treatment of operable (T\>/=2cm, N0-2,M0) primary breast cancer: To determine the pCR rate of 6 cycles vs. 8 cycles of docetaxel, doxorubicin and cyclophosphamide (TAC x 6 vs. TAC x 8)

Conditions

Breast Cancer

Keywords

Breast cancer; neoadjuvant therapy; pCR rates

Outcome Measures

Primary Outcomes (1)

• Determination of pCR rates

  To determine the iRR rate of 4 cycles of docetaxel, doxorubicin and cyclophosphamide (TAC) and of 4 cycles of vinorelbine and capecitabine (NX) (TAC-NX) as a salvage treatment

  2010

Secondary Outcomes (4)

• To determine the toxicity and compliance to each arm

  2010

• To determine the breast conservation rate in each arm

  2010

• To determine the disease-free and overall survival in each arm

  2010

• To determine the specificity and sensitivity of a presurgical core biopsy to predict the degree of pathologic tumor regression

  2010

Study Arms (4)

resp: 4xTAC

EXPERIMENTAL

Patients sufficiently responding (iPR, iCR) will recieve 4 further cycles of TAC

Drug: TAC

resp: 6xTAC

EXPERIMENTAL

Patients sufficiently responding (iPR, iCR) will recieve 6 further cycles of TAC

Drug: TAC

nonResp: 4xTAC

EXPERIMENTAL

Patients non-sufficiently responding (iNC) will recieve 4 further cycles of TAC

Drug: TAC

nonResp: 4xNX

EXPERIMENTAL

Patients non-sufficiently responding (iNC) will recieve 4 further cycles of NX

Drug: NX

Interventions

TAC DRUG

Docetaxel 75 mg/m² as a 1 hour i.v. infusion on day 1 every 3 weeks in combination with Doxorubicin 50 mg/m² as an i.v. bolus and Cyclophosphamide 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks

nonResp: 4xTAC; resp: 4xTAC; resp: 6xTAC

NX DRUG

Vinorelbine 25 mg/m² as a \< 10 min i.v. infusion on days 1 and 8 repeated every 3 weeks and Capecitabine 2000 mg/m² orally in 2 daily doses on days 1-14 repeated every 3 weeks

nonResp: 4xNX

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures.
• Complete baseline documentation sent to SKM CRS.
• Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration 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 in maximum diameter. The leasion has to be measurable in two-dimensions by sonography. In case of inflammatory disease the extent of inflammation can be used as measurable lesion. The following tumor stages are eligible:
• Palpable breast tumor size of \> 2 cm without involvement of the skin or muscle or evidence of inflammatory disease (T2-3). Clinical N0-2. (Study population I)
• Primary tumor with clinical involvement of skin or muscle or clinically evidence of inflammatory breast cancer (T4 a-d) or clinical N3 including supraclavicular nodes. (Study population II). In patients with multifocal or multicentric breast cancer, the largest lesion should be measured.
• Age \> 18 years.
• Karnofsky Performance status index \> 80%.
• Normal cardiac function must be confirmed by LVEF or shortening fraction (echocardiography or MUGA scan respectively) within 3 months prior to registration. The result must be above the normal limit of the institution.
• Laboratory requirements (within 14 days prior to registration):
• Hematology:
• Neutrophils \> 2.0 x 109/L and
• Platelets \> 100 x 109/L and
• Hemoglobin \> 10 g/dL
• Hepatic function:

You may not qualify if:

• Early breast cancer with a tumor size of \< 2 cm measured by palpation.
• Patients with low or moderate risk. These patients are defined as having none of the following risk factors: Age \< 36 years, cT\> 5cm, ER and PR negative, cN+, or Grade III.
• Evidence of distant metastasis.
• Prior chemotherapy for any malignancy.
• Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment.
• Pre-existing motor or sensory neuropathy of a severity \> grade 2 by NCI criteria.
• Other serious illness or medical condition:
• previous malignant disease with a disease-free survival of less than 5 years (except CIS of the Cervix and non-melanomatous skin cancer.
• congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year prior to study entry, uncontrolled arterial hypertension or high-risk uncontrolled arrhythmias.
• history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
• active uncontrolled infection.
• active peptic ulcer, unstable diabetes mellitus.
• Chronic treatment with corticosteroids unless initiated \> 6 months prior to study entry and at low dose (\</= 20 mg methylprednisolone or equivalent).
• Concurrent treatment with sex hormones. Prior treatment must be stopped before study entry.
• Definite contraindications for the use of corticosteroids.

Sponsors & Collaborators

• GBG Forschungs GmbH: lead
• Roche Pharma AG: collaborator
• Sanofi: collaborator
• Amgen: collaborator
• Goethe University: collaborator

Related Publications (10)

• von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M; German Breast Group. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst. 2008 Apr 16;100(8):542-51. doi: 10.1093/jnci/djn085. Epub 2008 Apr 8.

  PMID: 18398097 RESULT

• Costa SD, Loibl S, Kaufmann M, Zahm DM, Hilfrich J, Huober J, Eidtmann H, du Bois A, Blohmer JU, Ataseven B, Weiss E, Tesch H, Gerber B, Baumann KH, Thomssen C, Breitbach GP, Ibishi S, Jackisch C, Mehta K, von Minckwitz G. Neoadjuvant chemotherapy shows similar response in patients with inflammatory or locally advanced breast cancer when compared with operable breast cancer: a secondary analysis of the GeparTrio trial data. J Clin Oncol. 2010 Jan 1;28(1):83-91. doi: 10.1200/JCO.2009.23.5101. Epub 2009 Nov 9.

  PMID: 19901111 RESULT

• Rody A, Karn T, Gatje R, Ahr A, Solbach C, Kourtis K, Munnes M, Loibl S, Kissler S, Ruckhaberle E, Holtrich U, von Minckwitz G, Kaufmann M. Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. Breast. 2007 Feb;16(1):86-93. doi: 10.1016/j.breast.2006.06.008. Epub 2006 Sep 28.

  PMID: 17010609 RESULT

• Leichsenring J, Vladimirova V, Solbach C, Karn T, Ataseven B, Sinn BV, Barinoff J, Muller V, Blohmer JU, Schem C, Engels K, Marme F, Fisseler-Eckhoff A, Fasching PA, Stickeler E, van Mackelenbergh M, Denkert C, Stenzinger A, Loibl S, Groschel S. EVI1 expression in early-stage breast cancer patients treated with neoadjuvant chemotherapy. BMC Cancer. 2022 Oct 5;22(1):1040. doi: 10.1186/s12885-022-10109-1.

  PMID: 36195836 DERIVED

• Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

  PMID: 34037241 DERIVED

• Lindner JL, Loibl S, Denkert C, Ataseven B, Fasching PA, Pfitzner BM, Gerber B, Gade S, Darb-Esfahani S, Sinn BV, Huober J, Engels K, Tesch H, Karn T, Pommerenke F, Liedtke C, Untch M, Muller V, Rack B, Schem C, von Minckwitz G. Expression of secreted protein acidic and rich in cysteine (SPARC) in breast cancer and response to neoadjuvant chemotherapy. Ann Oncol. 2015 Jan;26(1):95-100. doi: 10.1093/annonc/mdu487. Epub 2014 Oct 29.

  PMID: 25355716 DERIVED

• Darb-Esfahani S, von Minckwitz G, Denkert C, Ataseven B, Hogel B, Mehta K, Kaltenecker G, Rudiger T, Pfitzner B, Kittel K, Fiedler B, Baumann K, Moll R, Dietel M, Eidtmann H, Thomssen C, Loibl S. Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes. BMC Cancer. 2014 Jul 28;14:546. doi: 10.1186/1471-2407-14-546.

  PMID: 25070172 DERIVED

• von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, Gerber B, Hanusch C, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Kummel S, Paepke S, Schneeweiss A, Untch M, Zahm DM, Mehta K, Loibl S. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013 Oct 10;31(29):3623-30. doi: 10.1200/JCO.2012.45.0940. Epub 2013 Sep 3.

  PMID: 24002511 DERIVED

• Sinn BV, von Minckwitz G, Denkert C, Eidtmann H, Darb-Esfahani S, Tesch H, Kronenwett R, Hoffmann G, Belau A, Thommsen C, Holzhausen HJ, Grasshoff ST, Baumann K, Mehta K, Dietel M, Loibl S. Evaluation of Mucin-1 protein and mRNA expression as prognostic and predictive markers after neoadjuvant chemotherapy for breast cancer. Ann Oncol. 2013 Sep;24(9):2316-24. doi: 10.1093/annonc/mdt162. Epub 2013 May 9.

  PMID: 23661292 DERIVED

• von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Konecny GE, Denkert C, Nekljudova V, Mehta K, Loibl S. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012 May 20;30(15):1796-804. doi: 10.1200/JCO.2011.38.8595. Epub 2012 Apr 16.

  PMID: 22508812 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Gunter von Minckwitz, MD

  GBG Forschungs GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2007
• First Posted: October 16, 2007
• Study Start: September 1, 2002
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: February 4, 2021

Record last verified: 2021-02