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Breast CancerPhase 2/3neo-TNNCT01057069

Neo Adjuvant Chemotherapy in Triple Negative Breast Cancer

A Phase 2/3 study testing Carboplatin and Paclitaxel, Doxorubicin, cyclophosphamide and Doxorubicin, cyclophosphamide, carboplatin, thiotepa, cyclophosphamide in people with Breast Cancer, run by The Netherlands Cancer Institute at 14 sites in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study aims to compare the response of triple-negative breast cancer with deficient homologous recombination to intensified alkylating chemotherapy versus standard chemotherapy with dose dense AC and/or Docetaxel-Capecitabine. Read more about this study

Who is it for?
Ages 18 to 59 years
Conditions the study is for
Breast Cancer
What is being tested?
Carboplatin and Paclitaxel, Doxorubicin, cyclophosphamide and Doxorubicin, cyclophosphamide, carboplatin, thiotepa, cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
310 participants
Where
14 sitesNetherlands
Study dates
Jan 2010to Dec 2029
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

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 59 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Proven infiltrating breast cancer with either a primary tumor over 2 cm in size (MRI or ultrasound examination) and/or cytologically proven spread to the axillary lymph nodes.
  • Patients with 'locally advanced breast cancer' are consequently eligible, including those with ipsilateral supraclavicular lymph node metastases.
  • The tumor must be HER2/neu-negative (either score 0 or 1 at immunohistochemistry or negative at in situ hybridization [CISH or FISH] in case of score 2 or 3 at immunohistochemistry).
  • The tumor must be Estrogen receptor (ER) -negative (< 10% nuclear staining at IHC) and Progesterone receptor (PR) -negative (< 10% nuclear staining at IHC). However, the rare tumors that are ER-negative and PR-positive will be eligible, if this pattern of hormone receptor expression can be verified in the NKI-AVL reference pathology lab.
  • Age 18 to 59 years; patients older than 59 years may be included when considered 'biologically 59 years or younger' (as judged by the investigator).
  • Performance status: WHO 0 or I.
Show all 10Show fewer
  • Adequate bone marrow function (W.B.C. count > 3.0 x 109/l, platelets > 100 x 109/l).
  • Adequate hepatic function (ALAT, ASAT and bilirubin < 2 x upper limit of normal, or minor abnormalities of these tests judged to be of no consequence by the study coordinator).
  • Adequate renal function (creatinine clearance > 60 ml/min).
  • Informed consent

Who cannot join

  • Previous radiation therapy or chemotherapy.
  • Other malignancy except carcinoma in situ, unless the other malignancy was treated 5 or more years ago with curative intent without the use of chemotherapy or radiation therapy.
  • Pregnancy or breast feeding.
  • Evidence of distant metastases. Staging examinations must have included a chest roentgenogram, an ultrasound examination of the liver and an isotope bone scan. Abnormal uptake on the isotope bone scan can only be accepted if bone metastases were excluded by MRI

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Netherlands14 sites

  • Medisch Centrum Alkmaar

    Alkmaar, 1815 JD

  • NKI-AVL

    Amsterdam, 1066 CX

  • OLVG

    Amsterdam, 1090 HM

  • Reinier de Graaf Groep

    Delft, 2625 AD

  • Deventer Ziekenhuis

    Deventer, 7400 GC

  • Albert Schweitzer ziekenhuis

    Dordrecht

  • Ziekenhuis Gelderse Vallei

    Ede

  • Kennemer Gasthuis

    Haarlem, 2000AK

  • Atrium Medisch Centrum Parkstad

    Heerlen, 6401 CX

  • Spaarne Ziekenhuis

    Hoofddorp, 2130 AT

  • LUMC

    Leiden, 2300 RC

  • Maasstad ziekenhuis

    Rotterdam, 3007 AC

  • Medisch Centrum Haaglanden

    The Hague, 2501 CK

  • Isala Klinieken

    Zwolle, 8000 GK

Other trials in Netherlands

About this study

Official title: Randomized Phase II/III Study of Individualized Neoadjuvant Chemotherapy in ' Triple Negative' Breast Tumors

This study aims to compare the response of triple-negative breast cancer with deficient homologous recombination to intensified alkylating chemotherapy versus standard chemotherapy with dose dense AC and/or Docetaxel-Capecitabine.

Read the detailed description

Homologous Recombination (HR) is a DNA repair mechanism that can repair double-strand DNA breaks. It is the only reliable repair mechanism that can repair the consequences of DNA adducts caused by bifunctional alkylating agents (such as cyclophosphamide, thiotepa or carboplatin). Alternative DNA repair mechanisms exist, but these unavoidably induce DNA mutations, deletions and chromosome aberrations, giving give rise to genetic instability. HRD may be a consequence of inactivation of the BRCA-1 or BRCA-2 genes (as in hereditary breast cancer), but it may also be caused by defects in the Fanconi anemia pathway or by amplification of the EMSY gene. HRD is present in breast cancer cells but not in healthy cells of BRCA-1 or BRCA-2 mutation carriers, and also in about half of the sporadic triple-negative breast cancers.

This phase II/III controlled multicenter trial will investigate the ability of individualized chemotherapy to improve the objective response rate of 'triple-negative' breast cancer (estrogen receptor and progesterone receptor-negative, no HER2 amplification) to preoperative (neoadjuvant) chemotherapy. It will answer the question whether intensified alkylating chemotherapy improves the response rate of tumors with a Homologous Recombination Defect (HRD) and it will gather data required for the design of a phase III study documenting the efficacy of response monitoring by contrast-enhanced MRI in TN breast cancer without HRD.

Conditions
Breast Cancer
Being tested
Carboplatin and Paclitaxel, Doxorubicin, cyclophosphamide, Doxorubicin, cyclophosphamide, carboplatin, thiotepa, cyclophosphamide
Keywords
Neo adjuvant, Triple negative, primary tumor over 2 cm and/or positive lymphnodes
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carboplatin and PaclitaxelDrug

    Also called Carboplatin, Paclitaxel

    Carboplatin AUC = 6, Q 3 weeks, 3 courses Paclitaxel 80 mg/m2, weekly, 9 administrations

  • Doxorubicin, cyclophosphamideDrug

    Two-weekly administrations of 600 mg/m2 cyclophosphamide and 60 mg/m2 doxorubicin PEG-filgrastim (Neulasta(r)) will be administered on the day following chemotherapy.

  • Doxorubicin, cyclophosphamide, carboplatin, thiotepa, cyclophosphamideDrug

    One course of of 600 mg/m2 cyclophosphamide and 60 mg/m2 doxorubicin. PEG-filgrastim (Neulasta(r)) will be administered on the day following chemotherapy.

    This course is followed by Peripheral Blood Progenitor Cell (PBPC) harvest and tandem intermediate-dose alkylating therapy (miniCTC, carboplatin 800 mg/m2, thiotepa 250 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion.

Study groups in NCT01057069
Study groupRoleWhat they receive
HRD; 1x ddAC, 2x tCTCExperimentalHRD positive tumors; irrespective of response; - a fourth course of AC followed by Peripheral Blood Progenitor Cell (PBPC) harvest and tandem intermediate-dose alkylating therapy (miniCTC, carboplatin 800 mg/m2, thiotepa 250 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion.
Receives: Drug: Doxorubicin, cyclophosphamide, carboplatin, thiotepa, cyclophosphamide
HRD; 3x CPActive comparatorHRD tumors; any response to 3x ddAC; 3 courses of CP
Receives: Drug: Carboplatin and Paclitaxel
non-HRD;3x CPActive comparatornon-HRD tumors; unfavourable response to 3x ddAC; 3 courses of Carboplatin and Paclitaxel
Receives: Drug: Carboplatin and Paclitaxel
non-HRD; response; 3x ddACActive comparatornon-HRD tumors; favourable response to 3x ddAC; 3 more courses of ddAC
Receives: Drug: Doxorubicin, cyclophosphamide
non-HRD; response; 3x CPActive comparatornon-HRD tumors; favourable response to 3x ddAC; 3 courses of Carboplatin and Paclitaxel
Receives: Drug: Carboplatin and Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary endpoint (HRD tumors): Average Neoadjuvant Response Index (NRI) after intensified alkylating therapy in comparison to that after 'standard' neoadjuvant chemotherapy. Primary endpoint (non-HRD tumors): Average Neoadjuvant Response Index (NRI)

    Measured: end of neo adjuvant chemotherapy

Secondary outcomes (1)

  1. Recurrence-free survival and overall survival.

    Measured: every year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2010 (estimated)
  2. Study startJan 2010
  3. Primary completionJun 2023 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

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
310 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01057069
Sponsor's protocol ID
M09TNM
Other IDs
2009-015238-31, 2009
Acronym
neo-TN
Status last verified
Oct 2022
First submitted
26 Jan 2010
Last updated
12 Oct 2022
Results posted
No
Data monitoring committee
No

Publications

  • Rodenhuis S, Mandjes IAM, Wesseling J, van de Vijver MJ, Peeters MTDFV, Sonke GS, Linn SC. A simple system for grading the response of breast cancer to neoadjuvant chemotherapy. Ann Oncol. 2010 Mar;21(3):481-487. doi: 10.1093/annonc/mdp348. Epub 2009 Aug 28.

    PubMed 19717533

  • Vliek S, Hilbers FS, van Werkhoven E, Mandjes I, Kessels R, Kleiterp S, Lips EH, Mulder L, Kayembe MT, Loo CE, Russell NS, Vrancken Peeters MTFD, Holtkamp MJ, Schot M, Baars JW, Honkoop AH, Vulink AJE, Imholz ALT, Vrijaldenhoven S, van den Berkmortel FWPJ, Meerum Terwogt JM, Schrama JG, Kuijer P, Kroep JR, van der Padt-Pruijsten A, Wesseling J, Sonke GS, Gilhuijs KGA, Jager A, Nederlof P, Linn SC. High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: the randomized phase III NeoTN trial. NPJ Breast Cancer. 2023 Sep 9;9(1):75. doi: 10.1038/s41523-023-00580-9.

    PubMed 37689749

  • Miquel-Cases A, Retel VP, van Harten WH, Steuten LM. Decisions on Further Research for Predictive Biomarkers of High-Dose Alkylating Chemotherapy in Triple-Negative Breast Cancer: A Value of Information Analysis. Value Health. 2016 Jun;19(4):419-30. doi: 10.1016/j.jval.2016.01.015. Epub 2016 Apr 6.

    PubMed 27325334

  • Miquel-Cases A, Steuten LM, Retel VP, van Harten WH. Early stage cost-effectiveness analysis of a BRCA1-like test to detect triple negative breast cancers responsive to high dose alkylating chemotherapy. Breast. 2015 Aug;24(4):397-405. doi: 10.1016/j.breast.2015.03.002. Epub 2015 Apr 28.

    PubMed 25937263

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Carboplatin and Paclitaxel, Doxorubicin, cyclophosphamide and Doxorubicin, cyclophosphamide, carboplatin, thiotepa, cyclophosphamide in people with Breast Cancer, run by The Netherlands Cancer Institute at 14 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 10 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 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 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?

This study is still under way. Results are not available in the source record yet.

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?

Primary endpoint (HRD tumors): Average Neoadjuvant Response Index (NRI) after intensified alkylating therapy in comparison to that after 'standard' neoadjuvant chemotherapy. Primary endpoint (non-HRD tumors): Average Neoadjuvant Response Index (NRI) (time frame: end of neo adjuvant 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 NCT01057069, which also lists 4 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 12 Oct 2022.

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