Breast CancerPhase 2/3ICE-IINCT01204437
Adjuvant Chemotherapy for Elderly Non Frail Patients With an Increased Risk for Relapse of a Primary Carcinoma of the Breast
A Phase 2/3 study testing Epirubicin, Cyclophosphamide, Cyclophosphamide, Methotrexate, 5 FU and Capecitabine, Nab-Paclitaxel in people with Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Epirubicin, Cyclophosphamide, Cyclophosphamide, Methotrexate, 5 FU and Capecitabine, Nab-Paclitaxel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2009to Jan 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Written informed consent for all study procedures must be obtained and documented according to local regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation must be sent to GBG Forschungs GmbH.
- Histological confirmed unilateral or bilateral primary carcinoma of the breast.
- Female and male breast cancer patients with age at first histologically diagnosis and axilla dissection ≥ 65 years.
- 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.
- No evidence for distant metastasis at bone scan, liver ultrasound and chest x-ray.
Show all 12Show fewer
- Patients with stage pT3/4 or pN2/3 (≥ 4 involved lymph nodes) irrespective of additional risk factors.
- 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.
- ECOG Performance Status <= 2.
- Charlson Scale <= 2.
- Estimated life expectancy of at least 5 years (irrespective of breast cancer diagnosis).
- 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.
Who cannot join
- Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency.
- Low risk patient according to risk assessment.
- 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.
- Previously or currently one of the following medical conditions:
- pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI-CTC criteria;
Show all 17Show fewer
- 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.
- Time since axillary dissection > 3 months.
- Locally advanced, non-operable breast cancer.
- Previous invasive breast carcinoma.
- Prior chemotherapy for any malignancy.
- Concurrent specific systemic anti-tumor treatment or treatment with experimental compounds within the last 6 months.
- Concurrent treatment with other tumor specific experimental drugs. Participation in another clinical trial with any investigational not marketed drug.
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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):
- 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).
- To compare the overall survival (OS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs nab-paclitaxel in combination with capecitabine (PX).
- To analyze the efficacy of treatments in subgroups according to clinical stratification factors.
- To determine prognostic factors on tumor tissue collected from primary surgery and to correlate them with study treatment effect.
- To compare the geriatric assessments scores (Charlson, VES-13, IADL, G8) at baseline and end of therapy.
- Conditions
- Breast Cancer
- Being tested
- Epirubicin, Cyclophosphamide, Cyclophosphamide, Methotrexate, 5 FU, Capecitabine, Nab-Paclitaxel
- Keywords
- adjuvant chemotherapy, primary carcinoma, elderly non frail patients, EC, CMF, Capecitabine, Nab-Paclitaxel
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epirubicin, CyclophosphamideDrug
4 cycles of chemotherapy with epirubicin plus cyclophosphamide (EC) on day 1 q22
Cyclophosphamide, Methotrexate, 5 FUDrug
6 cycles CMF on days 1 and 8 q29 Cyclophosphamide (500mg/qm), Methotrexate (40 mg/qm), 5 FU (600mg/qm)
Capecitabine, Nab-PaclitaxelDrug
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
| Study group | Role | What they receive |
|---|---|---|
| EC standard chemotherapy 4 cycles | Active comparator | Not described Receives: Drug: Epirubicin, Cyclophosphamide |
| CMF standard chemotherapy 6 cycles | Active comparator | Not described Receives: Drug: Cyclophosphamide, Methotrexate, 5 FU |
| Nab-Paclitaxel + Capecitabine 6 cycles | Experimental | 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 Receives: Drug: Capecitabine, Nab-Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the compliance and safety of epirubicin plus cyclophosphamide or CMF (EC/CMF) and nab-paclitaxel in combination with capecitabine (PX).
Measured: 4 months after Last Patient Out
Secondary outcomes (5)
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).
Measured: After 4.5 years of Follow Up
To compare the overall survival (OS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs nab-paclitaxel in combination with capecitabine (PX).
Measured: After 4.5 years of Follow Up
To analyze the efficacy of treatments in subgroups according to clinical stratification factors.
Measured: After 4.5 years of Follow Up
To determine prognostic factors on tumor tissue collected from primary surgery and to correlate them with study treatment effect.
Measured: After 4.5 years of Follow Up
To compare the geriatric assessment scores (Charlson, VES-13, IADL, G8) at baseline and end of therapy
Measured: 4 months after Last Patient Out
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2010 (estimated)
- Study startMar 2009
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gunter von Minckwitz, Prof., Principal investigator, GBG Forschungs GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01204437
- Sponsor's protocol ID
- GBG 52
- Other IDs
- 2008-003995-23, 2008
- Acronym
- ICE-II
- Status last verified
- Feb 2016
- First submitted
- 10 Sep 2010
- Last updated
- 10 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34037241
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01204437
- Acronym / sponsor ID
- ICE-II / GBG 52
- Conditions
- Breast Cancer
- Keywords
- adjuvant chemotherapy, primary carcinoma, elderly non frail patients, EC, CMF, Capecitabine, Nab-Paclitaxel
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 17 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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):
- 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).
- To compare the overall survival (OS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs nab-paclitaxel in combination with capecitabine (PX).
- To analyze the efficacy of treatments in subgroups according to clinical stratification factors.
- To determine prognostic factors on tumor tissue collected from primary surgery and to correlate them with study treatment effect.
- To compare the geriatric assessments scores (Charlson, VES-13, IADL, G8) at baseline and end of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EC standard chemotherapy 4 cycles | Active comparator | Drug: Epirubicin, Cyclophosphamide |
| CMF standard chemotherapy 6 cycles | Active comparator | Drug: Cyclophosphamide, Methotrexate, 5 FU |
| Nab-Paclitaxel + Capecitabine 6 cycles | Experimental | Drug: Capecitabine, Nab-Paclitaxel6 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 |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (12 listed)
- Written informed consent for all study procedures must be obtained and documented according to local regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation must be sent to GBG Forschungs GmbH.
- Histological confirmed unilateral or bilateral primary carcinoma of the breast.
- Female and male breast cancer patients with age at first histologically diagnosis and axilla dissection ≥ 65 years.
- 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.
Key exclusion criteria (17 listed)
- Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency.
- Low risk patient according to risk assessment.
- 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.
- Previously or currently one of the following medical conditions:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Epirubicin, Cyclophosphamide4 cycles of chemotherapy with epirubicin plus cyclophosphamide (EC) on day 1 q22 | Drug | EC standard chemotherapy 4 cycles |
| Cyclophosphamide, Methotrexate, 5 FU6 cycles CMF on days 1 and 8 q29 Cyclophosphamide (500mg/qm), Methotrexate (40 mg/qm), 5 FU (600mg/qm) | Drug | CMF standard chemotherapy 6 cycles |
| Capecitabine, Nab-Paclitaxel6 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 | Nab-Paclitaxel + Capecitabine 6 cycles |
Primary outcome
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
5 secondary outcomes
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
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
To analyze the efficacy of treatments in subgroups according to clinical stratification factors.
Time frame: After 4.5 years of Follow Up
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2016.
- Derived from this study: PubMed 34037241Hoon 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.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gunter von Minckwitz, Prof. principal investigator
GBG Forschungs GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Epirubicin, Cyclophosphamide, Cyclophosphamide, Methotrexate, 5 FU and Capecitabine, Nab-Paclitaxel in people with Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01204437, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2016.