A Study to Compare ETC vs. EC-TX and Ibandronate vs. Observation in Patients With Node-positive Primary Breast Cancer (GAIN)

NCT00196872 | Completed Phase 3

• 2 other identifiers: GBG 33GAIN
• Study Type: interventional
• Target: 3,000
• Locations: 1 country
• Sites: 1

Brief Summary

In the recent AGO-study, a dose-dense and dose-intensified sequence of Epirubicin - Paclitaxel - Cyclophosphamide has shown superior efficacy compared to a conventionally dosed sequence of Epirubicin / Cyclophosphamid and Paclitaxel and was therefore chosen as standard treatment in this study. The experimental arm of EC-TX combines several strategies: the combination of EC will be administered every 2 weeks as a dose-dense regimen, the combination of TX can also be considered as dose-dense due to the weekly application of paclitaxel. Furthermore there is clinical evidence, that a combination of capecitabine and Paclitaxel provide synergistic effects with improved tumour response. A randomized phase III study could demonstrate a survival benefit of a combination of capecitabine with Docetaxel in patients with metastatic breast cancer. This synergistic effect is probably based on the preclinical observed taxane-mediated up-regulation of thymidine phosphorylase in the tumour cell, which give drive to an increased transformation of capecitabine to its active form 5-Fluorouracil. Apart from this synergy, the EC-TX regimen includes now 4 highly active compounds for the treatment of breast cancer. The total doses of Epirubicin and Paclitaxel are identical in both arms. The dosage of Cyclophosphamide is lower in the experimental arm, which is preferred due to the induction of leukaemia at higher doses of Cyclophosphamide. The duration of both arms with 18 and 20 weeks is nearly similar. The 2 by 2 factorial design of the trial provides the additional possibility to explore the efficacy of a bisphosphonate as another strategy to further improve the prognosis of node positive breast cancer.

Conditions

Breast Cancer

Keywords

dose dense sequence; dose dense combination; node positive disease

Outcome Measures

Primary Outcomes (2)

• A: To compare the disease-free survival after adjuvant chemotherapy with "ETC" (Arm A1) or "EC-TX" (Arm A2) in patients with primary node-positive breast cancer.

  US-law not applicable

• B: To compare the disease-free survival with (Arm B1) or without ibandronate (Arm B2) treatment for 2 years in patients with primary node-positive breast cancer

  US-law not applicable

Secondary Outcomes (8)

• To compare overall survival between arms A1 vs. A2 and B1 vs. B2

  US-law not applicable

• To evaluate the compliance in arms A1 vs. A2 and in B1

  US-law not applicable

• To compare the safety between arms A1 vs. A2 and B1 vs. B2

  US-law not applicable

• To assess the rate of responders to erythropoesis stimulating factors in arm A1 and A2

  US-law not applicable

• To compare the incidence of secondary primaries between arms A1 vs. A2

  US-law not applicable

Study Arms (4)

ETC-with Ibandronat

EXPERIMENTAL

ETC follwoed by Ibandronat

Drug: Epirubicine; Drug: Cyclophosphamide; Drug: Taxol; Drug: Ibandronat

ETC without Ibandronat

EXPERIMENTAL

ETC not followed by Ibandronat

Drug: Epirubicine; Drug: Cyclophosphamide; Drug: Taxol

EC-TX with Ibandronat

EXPERIMENTAL

EC-TX followed by Ibandronat

Drug: Epirubicine; Drug: Cyclophosphamide; Drug: Taxol; Drug: Xeloda; Drug: Ibandronat

EC-TX without Ibandronat

EXPERIMENTAL

EC-TX not followed by Ibandronat

Drug: Epirubicine; Drug: Cyclophosphamide; Drug: Taxol; Drug: Xeloda

Interventions

Epirubicine DRUG

Epirbubicne is given

EC-TX with Ibandronat; EC-TX without Ibandronat; ETC without Ibandronat; ETC-with Ibandronat

Cyclophosphamide DRUG

Cyclophosphamide is given

EC-TX with Ibandronat; EC-TX without Ibandronat; ETC without Ibandronat; ETC-with Ibandronat

Taxol DRUG

Taxol is given

EC-TX with Ibandronat; EC-TX without Ibandronat; ETC without Ibandronat; ETC-with Ibandronat

Xeloda DRUG

Xeloda is given

EC-TX with Ibandronat; EC-TX without Ibandronat

Ibandronat DRUG

Ibandronat is given

EC-TX with Ibandronat; ETC-with Ibandronat

Eligibility Criteria

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

You may qualify if:

• Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements, Histologically confirmed unilateral or bilateral primary carcinoma of the breast Age at diagnosis at least 18 years and biologically younger than 65 years Adequate surgical treatment with histological complete resection (R0) of the tumor and at least 10 axillary nodes At least one histological involved axillary or internal mammarian lymph node No evidence for distant metastasis after complete diagnostic work up Primary wound healing from breast surgery without signs of infection Performance Status ECOG \< 2 Estimated life expectancy of at least 10 years irrespective of the diagnosis of breast cancer The patient must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating center which could be the Principal or an Co- investigator's site

You may not qualify if:

• Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase (DHP) deficiency.
• Inadequate organ function including: ANC \< 1.5 G/l, Platelets \< 100 G/l , Transaminases, Creatinine or Bilirubin \> 1.25 times above upper normal limits (UNL), AP \> 3 times above UNL, Creatinine Clearance \< 30ml/min (if Creatinine is above UNL, according to Cockroft-Gault), severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study Insufficient and uncompensated cardiac function with LVEF below the normal range of the institution, history of severe heart disease, myocardial infarction within the last 6 months, cardiac arrhythmias LOWN II Evidence for infection including wound infections, HIV, Hepatitis Secondary malignancy, except curatively treated basalioma of the skin and carcinoma in situ of the cervix Time since axillary dissection \> 3 months (optimal \< 1 month) Non-operable breast cancer Previous and already (neoadjuvant or adjuvant) treated invasive breast carcinoma Previous or concurrent anti-tumor treatment for any reason Simultaneous therapy with Sorivudine or Brivudine as virostatics, immunosuppressive treatment or concurrent treatment with aminoglycosides Pregnancy or lactation period. Adequate non hormonal contraception is a prerequisite in premenopausal patients Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
• Male patients

Sponsors & Collaborators

• GBG Forschungs GmbH: lead

Study Sites (1)

Städtische Kliniken Frankfurt a.M.-Höchst

Frankfurt, Hessia, 65929, Germany

Location

Related Publications (4)

• Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

  PMID: 38979716 DERIVED

• Sturken C, Mobus V, Milde-Langosch K, Schmatloch S, Fasching PA, Ruschoff J, Stickeler E, Henke RP, Denkert C, Hanker L, Schem C, Vladimirova V, Karn T, Nekljudova V, Kohne CH, Marme F, Schumacher U, Loibl S, Muller V. TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer. BMC Cancer. 2021 Aug 14;21(1):920. doi: 10.1186/s12885-021-08656-0.

  PMID: 34391399 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

• Noske A, Mobus V, Weber K, Schmatloch S, Weichert W, Kohne CH, Solbach C, Ingold Heppner B, Steiger K, Muller V, Fasching P, Karn T, van Mackelenbergh M, Marme F, Schmitt WD, Schem C, Stickeler E, Loibl S, Denkert C. Relevance of tumour-infiltrating lymphocytes, PD-1 and PD-L1 in patients with high-risk, nodal-metastasised breast cancer of the German Adjuvant Intergroup Node-positive study. Eur J Cancer. 2019 Jun;114:76-88. doi: 10.1016/j.ejca.2019.04.010. Epub 2019 May 7.

  PMID: 31075727 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Epirubicin; Cyclophosphamide; Paclitaxel; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Volker Möbus, Prof. Dr.

  Städtische Kliniken Frankfurt a.M.-Höchst, Gotenstr. 6-8, 65929 Frankfurt, Germany

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: July 1, 2004
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: July 17, 2014

Record last verified: 2012-08

Locations

DE (1)