Adjuvant Chemotherapy for Elderly Non Frail Patients With an Increased Risk for Relapse of a Primary Carcinoma of the Breast (ICE II)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
German Breast Group
ClinicalTrials.gov Identifier:
NCT01204437
First received: September 10, 2010
Last updated: May 21, 2013
Last verified: May 2013
  Purpose

Although approximately 50% of new diagnosis breast cancers are in patients above the age of 65, elderly people remain substantially under-represented in clinical trials, and therefore are under-treated. A recent trial of the CALBG in patient's ≥ 65 years with medium risk of breast cancer demonstrated an improved disease-free and overall survival for those treated with AC or CMF compared to those treated with capecitabine alone.

The primary aim of the ICE II trial is to determine the compliance and toxicity of epirubicin plus cyclophosphamide (EC) or CMF versus nab-paclitaxel plus capecitabine as adjuvant therapy in non frail elderly patients.


Condition Intervention Phase
Breast Cancer
Drug: Epirubicin, Cyclophosphamide
Drug: Cyclophosphamide, Methotrexate, 5 FU
Drug: Capecitabine, Nab-Paclitaxel
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Investigational Randomized Study on Epirubicin Plus Cyclophospamide (EC) or Cyclophosphamide Plus Methotrexat Plus 5-fluorouracil (CMF) Versus Nab-paclitaxel Plus Capecitabine as Adjuvant Chemotherapy for Elderly Non Frail Patients With an Increased Risk for Relapse of a Primary Carcinoma of the Breast

Resource links provided by NLM:


Further study details as provided by German Breast Group:

Primary Outcome Measures:
  • To determine the compliance and safety of epirubicin plus cyclophosphamide or CMF (EC/CMF) and nab-paclitaxel in combination with capecitabine (PX). [ Time Frame: 4 months after Last Patient Out ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To compare the disease-free survival (DFS) and distant disease free survival (DDFS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs. nab-paclitaxel in combination with capecitabine (PX). [ Time Frame: After 4.5 years of Follow Up ] [ Designated as safety issue: Yes ]
  • To compare the overall survival (OS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs nab-paclitaxel in combination with capecitabine (PX). [ Time Frame: After 4.5 years of Follow Up ] [ Designated as safety issue: Yes ]
  • To analyze the efficacy of treatments in subgroups according to clinical stratification factors. [ Time Frame: After 4.5 years of Follow Up ] [ Designated as safety issue: Yes ]
  • To determine prognostic factors on tumor tissue collected from primary surgery and to correlate them with study treatment effect. [ Time Frame: After 4.5 years of Follow Up ] [ Designated as safety issue: Yes ]
  • To compare the geriatric assessment scores (Charlson, VES-13, IADL, G8) at baseline and end of therapy [ Time Frame: 4 months after Last Patient Out ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 400
Study Start Date: March 2009
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: EC standard chemotherapy 4 cycles Drug: Epirubicin, Cyclophosphamide
4 cycles of chemotherapy with epirubicin plus cyclophosphamide (EC) on day 1 q22
Active Comparator: CMF standard chemotherapy 6 cycles Drug: Cyclophosphamide, Methotrexate, 5 FU
6 cycles CMF on days 1 and 8 q29 Cyclophosphamide (500mg/qm), Methotrexate (40 mg/qm), 5 FU (600mg/qm)
Experimental: Nab-Paclitaxel + Capecitabine 6 cycles
6 cycles of weekly nab-Paclitaxel 100 mg/m2 on days 1, 8, 15 q22 with a week of rest every 6 weeks in combination with capecitabine 2000 mg/m2, days 1 - 14 orally, divided into 2 daily doses every 3 weeks for 6 cycles
Drug: Capecitabine, Nab-Paclitaxel
6 cycles of weekly nab-paclitaxel 100 mg/m2 on days 1, 8, 15 q22 with a week of rest every 6 weeks in combination with capecitabine 2000 mg/m2, days 1 - 14 orally, divided into 2 daily doses every 3 weeks for 6 cycles

Detailed Description:

Primary Objective:

Phase II:

To determine the compliance and safety of epirubicin plus cyclophosphamide or CMF (EC/CMF) and nab-paclitaxel in combination with capecitabine (PX).

Secondary Objective(s):

  1. To compare the disease-free survival (DFS) and distant disease free survival (DDFS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs. nab-paclitaxel in combination with capecitabine (PX).
  2. To compare the overall survival (OS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs nab-paclitaxel in combination with capecitabine (PX).
  3. To analyze the efficacy of treatments in subgroups according to clinical stratification factors.
  4. To determine prognostic factors on tumor tissue collected from primary surgery and to correlate them with study treatment effect.
  5. To compare the geriatric assessments scores (Charlson, VES-13, IADL, G8) at baseline and end of therapy.
  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent for all study procedures must be obtained and documented according to local regulatory requirements prior to beginning specific protocol procedures.
  2. Complete baseline documentation must be sent to GBG Forschungs GmbH.
  3. Histological confirmed unilateral or bilateral primary carcinoma of the breast.
  4. Female and male breast cancer patients with age at first histologically diagnosis and axilla dissection ≥ 65 years.
  5. Adequate surgical treatment with complete resection (R0) of the tumor and ≥ 10 axillary nodes. Sole sentinel node biopsy is allowed if the sentinel node shows no tumor involvement.
  6. No evidence for distant metastasis at bone scan, liver ultrasound and chest x-ray.
  7. Patients with stage pT3/4 or pN2/3 (≥ 4 involved lymph nodes) irrespective of additional risk factors.
  8. Patients with stage pT1/2 and pN0/1 (0-3 involved lymph nodes) with an increased risk according to the clinico-pathological or uPA/PAI-1 criteria.
  9. ECOG Performance Status <= 2.
  10. Charlson Scale <= 2.
  11. Estimated life expectancy of at least 5 years (irrespective of breast cancer diagnosis).
  12. The patient must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre which could be the Principal or a Co- investigator's site.

Exclusion Criteria:

  1. Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency.
  2. Low risk patient according to risk assessment.
  3. Inadequate organ function including:

    Leucocytes < 3,5 G/l, Platelets < 100 G/l , Creatinine or Bilirubin above normal limits (1,25 above upper normal limit), Creatinine-Clearance below 50 ml/min, uncompensated cardiac function, severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study.

  4. Previously or currently one of the following medical conditions:

    • pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI-CTC criteria;
    • history of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent;
    • known or suspected congestive heart failure (> NYHA I) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (i.e. BP >150/100 mmHg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease;
    • Creatinine Clearance less than 50 ml/min;
    • another primary malignancy with an event-free survival of < 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix.
  5. Time since axillary dissection > 3 months.
  6. Locally advanced, non-operable breast cancer.
  7. Previous invasive breast carcinoma.
  8. Prior chemotherapy for any malignancy.
  9. Concurrent specific systemic anti-tumor treatment or treatment with experimental compounds within the last 6 months.
  10. Concurrent treatment with other tumor specific experimental drugs. Participation in another clinical trial with any investigational not marketed drug.
  11. Concurrent treatment with virostatic agents like sorivudine or analogues like brivudine, concurrent treatment with aminoglycosides, anticoagulants: heparin, warfarin as well as acetylic acid (e.g. Aspirin®) at a dose of > 325mg/day or clopidogrel at a dose of > 75 mg/day).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01204437

Locations
Germany
German Breast Group, GBG Forschungs GmbH
Neu-Isenburg, Germany, 63263
Sponsors and Collaborators
German Breast Group
Investigators
Principal Investigator: Gunter von Minckwitz, Prof. Dr. med. German Breast Group
  More Information

No publications provided

Responsible Party: German Breast Group
ClinicalTrials.gov Identifier: NCT01204437     History of Changes
Other Study ID Numbers: GBG 52, 2008-003995-23
Study First Received: September 10, 2010
Last Updated: May 21, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by German Breast Group:
adjuvant chemotherapy
primary carcinoma
elderly non frail patients
EC
CMF
Capecitabine
Nab-Paclitaxel

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Cyclophosphamide
Fluorouracil
Methotrexate
Capecitabine
Epirubicin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Abortifacient Agents, Nonsteroidal
Abortifacient Agents

ClinicalTrials.gov processed this record on July 26, 2014