Breast CancerPhase 3INTENSNCT00314977
Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable or Locally Advanced Breast Cancer.
A Phase 3 study testing Doxorubicin, Cyclophosphamide and Docetaxel in people with Breast Cancer, run by Radboud University Medical Center at 24 sites in Netherlands.
Trial summary
2 different treatment schedules may be used for neoadjuvant chemotherapy in breast cancer using adriamycin, cyclophosphamide and taxotere. The most optimal sequence- concurrent or sequential- is however unclear. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Doxorubicin, Cyclophosphamide and Docetaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 24 sitesNetherlands
- Study dates
- Feb 2006to Apr 2009
- Phase
- Phase 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 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women presenting with large resectable or locally advanced breast cancer (T2 ≥3 cm, T3, or T4, and/or LN positive)
- Measurable disease (breast and/or lymph nodes)
- No prior surgery other than biopsy and no prior chemotherapy or radiation therapy
- Age ≥18 years and age ≤70 years
- Karnofsky Performance score ≥70%
- Estrogen and/or progesterone receptor analysis performed on the primary tumour in the biopsy material
Show all 13Show fewer
- In case the tumor is ER/PgR ³ 50% positive, (neo)adjuvant hormonal therapy in stead of chemotherapy should be considered (e.g. in TEAM II study)
- Her2/neu receptor analysis performed on the primary tumour in the biopsy material
- Adequate bone marrow function (within 14 days prior to registration): WBC ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
- Adequate liver function (within 4 weeks prior to start treatment): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
- Adequate renal function (within 4 weeks prior to start treatment): the calculated creatinine clearance should be ≥50 mL/min
- Patients must be accessible for treatment and follow-up
- Written informed consent according to the local Ethics Committee requirements
Who cannot join
- Patients with advanced pulmonary disease of any cause (oxygen dependent)- Peripheral neuropathy > grade 2 whatever the cause
- Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrythmias
- Evidence of distant metastases (M1)
- Patients with a history of breast cancer
- Patients with a history of another malignancy (except basal cell skin carcinoma and carcinoma-in-situ of the uterine cervix) within 5 years of study entry- Pregnant or lactating women, or potentially fertile women not using adequate contraception
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
Netherlands24 sites
Jeroen Bosch Ziekenhuis
's-Hertogenbosch
Onze Lieve Vrouwe Gasthuis
Amsterdam
Rijnstate Ziekenhuis
Arnhem
Deventer Ziekenhuis
Deventer
Slingeland Hospital
Doetinchem
Catharina Ziekenhuis
Eindhoven
St. Anna Hospital
Geldrop
St. Jansdal Ziekenhuis
Harderwijk
Atrium Medisch Centrum
Heerlen
Elkerliek Ziekenhuis
Helmond
Spaarne Ziekenhuis
Hoofddorp
Leids Universitair Medisch Centrum (LUMC)
Leiden
Academical Hospital Maastricht (AZM)
Maastricht
St. Antonius Hospital
Nieuwegein
Canisius Wilhelmina Ziekenhuis
Nijmegen
Radboud University Medical Centre
Nijmegen
Waterland Hospital
Purmerend
Maasland Hospital
Sittard
HAGA Ziekenhuis
The Hague
St. Elisabeth Ziekenhuis
Tilburg
Mesos Medisch Centrum
Utrecht
UMC Utrecht
Utrecht
Maxima Medisch Centrum
Veldhoven
Zaans Medical Centre
Zaandam
About this study
Official title: Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable and/or Locally Advanced Breast Cancer. The INTENS Study
2 different treatment schedules may be used for neoadjuvant chemotherapy in breast cancer using adriamycin, cyclophosphamide and taxotere. The most optimal sequence- concurrent or sequential- is however unclear. The aim of the study is to compare the efficacy and tolerability of neoadjuvant chemotherapy with AC followed by T(adriamycin, cyclophosphamide, taxotere) versus TAC ( with upfront T) in patient with large resectable or locally advanced breast cancer.
- Conditions
- Breast Cancer
- Being tested
- Doxorubicin, Cyclophosphamide, Docetaxel
- Keywords
- Large resectable breast cancer, Locally advanced breast cancer, Neoadjuvant therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
Also called hydroxyldaunorubicin, adriamycin
doxorubicin (arm A:60 mg/m2) and arm B: 50 mg/m2)
CyclophosphamideDrug
Also called Cytoxan, Neosar, Revimmune
Cyclophosphamide: (arm A; 6000 mg/m2) an (arm B: 500 mg/m2)
DocetaxelDrug
Also called Taxotere
Docetaxel: (arm A: 100 mg/m2) and (arm B: 75 mg/m2)
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Cycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| B | Experimental | Cycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
The pathologic complete response rate to neoadjuvant chemotherapy.
Secondary outcomes (9)
The delivered chemotherapy dose and dose-intensity of both chemotherapy regimens
The tolerability (grade 3/4 CTC toxicities) of both chemotherapy regimens.
The clinical responses of neoadjuvant chemotherapy correlated to pathological responses after neoadjuvant chemotherapy.
The value of breast MRI in evaluating response to neoadjuvant chemotherapy as compared to clinical palpation, ultrasound techniques and histo-pathological outcome.
The false-negative rate of the sentinel node biopsy after neoadjuvant chemotherapy.
The disease-free and overall survival after 3 and 5 years follow-up.
The relation between pCR and DFS/OS.
The feasibility of the criteria for reporting pathological tumour response in surgical breast and axillary node resection specimens.
The prognostic and predictive value of tumour- and molecular markers, including ER, PgR, c-erbB2, microarray and other tumour characteristic analyses.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2006 (estimated)
- Study startFeb 2006
- Primary completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- V.C.G. Tjan-Heijnen, Principal investigator, AZM Maastricht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00314977
- Sponsor's protocol ID
- IKO 2005-01 / BOOG 2007-02
- Acronym
- INTENS
- Status last verified
- Mar 2010
- First submitted
- 14 Apr 2006
- Last updated
- 18 Mar 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Vriens BEPJ, Vriens IJH, Aarts MJB, van Gastel SM, van den Berkmortel FWPJ, Smilde TJ, van Warmerdam LJC, van Spronsen DJ, Peer PGM, de Boer M, Tjan-Heijnen VCG; Breast Cancer Trialists' Group of the Netherlands (BOOG). Improved survival for sequentially as opposed to concurrently delivered neoadjuvant chemotherapy in non-metastatic breast cancer. Breast Cancer Res Treat. 2017 Oct;165(3):593-600. doi: 10.1007/s10549-017-4364-8. Epub 2017 Jul 3.
PubMed 28674765Vriens BE, de Vries B, Lobbes MB, van Gastel SM, van den Berkmortel FW, Smilde TJ, van Warmerdam LJ, de Boer M, van Spronsen DJ, Smidt ML, Peer PG, Aarts MJ, Tjan-Heijnen VC; INTENS Study Group. Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer. Eur J Cancer. 2016 Jan;52:67-76. doi: 10.1016/j.ejca.2015.10.010. Epub 2015 Nov 30.
PubMed 26650831
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable and/or Locally Advanced Breast Cancer. The INTENS Study
- ClinicalTrials.gov ID
- NCT00314977
- Acronym / sponsor ID
- INTENS / IKO 2005-01 / BOOG 2007-02
- Conditions
- Breast Cancer
- Keywords
- Large resectable breast cancer, Locally advanced breast cancer, Neoadjuvant therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Sanofi, Amgen
- Study start
- Feb 2006
- Primary completion
- Apr 2009 (actual)
- First posted
- 17 Apr 2006 (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.
2 different treatment schedules may be used for neoadjuvant chemotherapy in breast cancer using adriamycin, cyclophosphamide and taxotere. The most optimal sequence- concurrent or sequential- is however unclear. The aim of the study is to compare the efficacy and tolerability of neoadjuvant chemotherapy with AC followed by T(adriamycin, cyclophosphamide, taxotere) versus TAC ( with upfront T) in patient with large resectable or locally advanced breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: DocetaxelCycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel |
| B | Experimental | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: DocetaxelCycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Women presenting with large resectable or locally advanced breast cancer (T2 ≥3 cm, T3, or T4, and/or LN positive)
- Measurable disease (breast and/or lymph nodes)
- No prior surgery other than biopsy and no prior chemotherapy or radiation therapy
- Age ≥18 years and age ≤70 years
- Karnofsky Performance score ≥70%
Key exclusion criteria (5 listed)
- Patients with advanced pulmonary disease of any cause (oxygen dependent)- Peripheral neuropathy > grade 2 whatever the cause
- Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrythmias
- Evidence of distant metastases (M1)
- Patients with a history of breast cancer
- Patients with a history of another malignancy (except basal cell skin carcinoma and carcinoma-in-situ of the uterine cervix) within 5 years of study entry- Pregnant or lactating women, or potentially fertile women not using adequate contraception
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 |
|---|---|---|
| DoxorubicinAlso: hydroxyldaunorubicin, adriamycindoxorubicin (arm A:60 mg/m2) and arm B: 50 mg/m2) | Drug | A, B |
| CyclophosphamideAlso: Cytoxan, Neosar, RevimmuneCyclophosphamide: (arm A; 6000 mg/m2) an (arm B: 500 mg/m2) | Drug | A, B |
| DocetaxelAlso: TaxotereDocetaxel: (arm A: 100 mg/m2) and (arm B: 75 mg/m2) | Drug | A, B |
Primary outcome
The pathologic complete response rate to neoadjuvant chemotherapy.
9 secondary outcomes
The delivered chemotherapy dose and dose-intensity of both chemotherapy regimens
The tolerability (grade 3/4 CTC toxicities) of both chemotherapy regimens.
The clinical responses of neoadjuvant chemotherapy correlated to pathological responses after neoadjuvant chemotherapy.
The value of breast MRI in evaluating response to neoadjuvant chemotherapy as compared to clinical palpation, ultrasound techniques and histo-pathological outcome.
The false-negative rate of the sentinel node biopsy after neoadjuvant chemotherapy.
The disease-free and overall survival after 3 and 5 years follow-up.
The relation between pCR and DFS/OS.
The feasibility of the criteria for reporting pathological tumour response in surgical breast and axillary node resection specimens.
The prognostic and predictive value of tumour- and molecular markers, including ER, PgR, c-erbB2, microarray and other tumour characteristic analyses.
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 18 Mar 2010.
- Derived from this study: PubMed 28674765Vriens BEPJ, Vriens IJH, Aarts MJB, van Gastel SM, van den Berkmortel FWPJ, Smilde TJ, van Warmerdam LJC, van Spronsen DJ, Peer PGM, de Boer M, Tjan-Heijnen VCG; Breast Cancer Trialists' Group of the Netherlands (BOOG). Improved survival for sequentially as opposed to concurrently delivered neoadjuvant chemotherapy in non-metastatic breast cancer. Breast Cancer Res Treat. 2017 Oct;165(3):593-600. doi: 10.1007/s10549-017-4364-8. Epub 2017 Jul 3.
- Derived from this study: PubMed 26650831Vriens BE, de Vries B, Lobbes MB, van Gastel SM, van den Berkmortel FW, Smilde TJ, van Warmerdam LJ, de Boer M, van Spronsen DJ, Smidt ML, Peer PG, Aarts MJ, Tjan-Heijnen VC; INTENS Study Group. Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer. Eur J Cancer. 2016 Jan;52:67-76. doi: 10.1016/j.ejca.2015.10.010. Epub 2015 Nov 30.
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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.
V.C.G. Tjan-Heijnen principal investigator
AZM Maastricht
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Doxorubicin, Cyclophosphamide and Docetaxel in people with Breast Cancer, run by Radboud University Medical Center at 24 sites in Netherlands.
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 13 inclusion and 5 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 18 Mar 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Netherlands. 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 phase mean?
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?
The pathologic complete response rate to neoadjuvant chemotherapy.. 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 NCT00314977, which also lists 2 linked publications.
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 18 Mar 2010; AzTrials last refreshed its copy on 5 Nov 2026.