Study of Nab-Paclitaxel in High Risk Early Breast Cancer

NCT01690702 | Completed Phase 3 DMC

• 1 other identifier: GBG 68
• Study Type: interventional
• Target: 2,886
• Locations: 1 country
• Sites: 1

Brief Summary

two-armed trial to compare E-nP-C against tailored dtEC-dtD in patients with high risk early breast cancer

Conditions

Breast Cancer

Keywords

breast cancer; tailored; high-risk

Outcome Measures

Primary Outcomes (1)

• invasive disease-free survival (IDFS)

  The IDFS is defined as the time period between the registration and the first invasive event. It will be analyzed after the end of the study by referring to data from GBG patient's registry.

  5 years

Secondary Outcomes (13)

• locoregional relapse-free survival (LRRFS)

  5 years

• overall survival (OS)

  5 years

• distant disease-free survival (DDFS)

  5 years

• local relapse-free survival (LRFS)

  5 years

• regional relapse-free survival (RRFS)

  5 years

Other Outcomes (1)

• prognostic/predictive factors

  5 years

Study Arms (2)

dtEC-dtD

ACTIVE COMPARATOR

Epirubicin and Cyclophosphamide with a tailored dose 4 cycles q2w followed by one additional week followed by Docetaxel with a tailored dose 4 cycles q2w.

Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Docetaxel

EnPC

EXPERIMENTAL

Epirubicin 150mg/qm 3 cycles q2w followed by nabPaclitaxel 260-330mg/qm (to be determined in run-in-phase) 3 cycles q2w followed by Cyclophosphamide 2000mg/qm 3 cycles q2w

Drug: Epirubicin; Drug: nab-Paclitaxel; Drug: Cyclophosphamide

Interventions

Epirubicin DRUG

EnPC; dtEC-dtD

nab-Paclitaxel DRUG

EnPC

Cyclophosphamide DRUG

EnPC; dtEC-dtD

Docetaxel DRUG

dtEC-dtD

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 for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
• Histologically confirmed unilateral or bilateral primary carcinoma of the breast.
• Age at diagnosis at least 18 years, female, and biologically not older than 65 years (but in any case not older than 70 years).
• In case of adjuvant therapy: Adequate surgical treatment with histological complete resection (R0) of the invasive breast tumor. Choice of axilla surgery is up to the participating site.
• Centrally confirmed ER/PgR/HER2 and Ki-67 status detected on surgical removed tissue (for adjuvant patients) or from core biopsy (for neoadjuvant patients). ER/PR positive is defined as ≥ 1% stained cells and HER2 positive is defined as IHC 3+ in \> 10% immunoreactive cells or FISH (or equivalent test) ratio ≥ 2.0. Formalin-fixed, paraffin-embedded (FFPE) breast tissue has to be sent to the Institute of Pathology at the Charité Berlin prior to randomization.
• High risk breast cancer as defined as:
• HER2 positive or triple-negative tumors irrespective of nodal status or
• Luminal B-like tumors (ER and/or PgR positive, HER2 negative, Ki-67 \> 20%) with involved lymph nodes or
• or more involved lymph nodes.
• Complete staging work-up within 3 months prior to randomization. All patients must have performed bilateral mammography, breast ultrasound, breast MRT (optional), chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRT and bone scan. In case of positive bone scan, bone X-ray (or CT or MRT) is mandatory. Other tests may be performed as clinically indicated.
• Karnofsky Performance status index ≥ 80%.
• Estimated life expectancy of at least 10 years irrespective of the diagnosis of breast cancer.
• Confirmed normal cardiac function by ECG and cardiac ultrasound (LVEF or shortening fraction) within 2 weeks prior to randomization. LVEF must be above 55%.
• Laboratory requirements:
• Hematology

You may not qualify if:

• Patients with Luminal A-like tumors (ER and or PgR positive, HER2 negative and Ki-67 ≤ 20%) and
• if neoadjuvant: \< cN2 or \< pN2(sn).
• if adjuvant: \< 4 involved lymph nodes.
• Non-operable breast cancer.
• In case of adjuvant therapy: time since axillary dissection or SLNB \> 3 months (optimal \< 1 month).
• Previous and already (neoadjuvant or adjuvant) treated invasive breast carcinoma.
• Previous malignant disease being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
• Known or suspected congestive heart failure (\> NYHA I) and/or coronary heart disease, angina pectoris requiring anti-anginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP \> 160/90mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
• Evidence for infection including wound infections, HIV, hepatitis.
• History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
• Pre-existing motor or sensory neuropathy of a severity ≥ grade 1 by NCI-CTCAE version 4.0.
• Other severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study.
• Previous or concurrent treatment with:
• concurrent chronic corticosteroids unless initiated \> 6 months prior to study entry and at low dose (≤ 10mg methylprednisolone or equivalent) except inhalative corticoids.
• concurrent sex hormones. Prior treatment must be stopped before study entry.

Sponsors & Collaborators

• GBG Forschungs GmbH: lead
• Celgene: collaborator
• Amgen: collaborator

Study Sites (1)

Klinikum Frankfurt Höchst

Frankfurt am Main, Hesse, 65929, Germany

Location

Related Publications (1)

• Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M, Wimberger P, Forberger A, Tesch H, Jackisch C, Schmatloch S, Reinisch M, Solomayer EF, Schmitt WD, Hanusch C, Fasching PA, Lubbe K, Solbach C, Huober J, Rhiem K, Marme F, Reimer T, Schmidt M, Sinn BV, Janni W, Stickeler E, Michel L, Stotzer O, Hahnen E, Furlanetto J, Seiler S, Nekljudova V, Untch M, Loibl S. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021 Aug;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6. Epub 2021 Jul 9.

  PMID: 34252375 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Epirubicin; 130-nm albumin-bound paclitaxel; Cyclophosphamide; Docetaxel

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

Study Officials

• Gunter von Minckwitz, Prof.

  GBG Forschungs GmbH

  STUDY CHAIR

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: August 29, 2012
• First Posted: September 24, 2012
• Study Start: September 1, 2012
• Primary Completion: September 30, 2018
• Study Completion: July 20, 2020
• Last Updated: February 2, 2021

Record last verified: 2021-02

Locations

DE (1)