Neo Adjuvant Chemotherapy in Triple Negative Breast Cancer

NCT01057069 | Active Not Recruiting Phase 2

• 2 other identifiers: M09TNM2009-015238-31
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

Breast Cancer

Keywords

Neo adjuvant; Triple negative; primary tumor over 2 cm and/or positive lymphnodes

Outcome Measures

Primary Outcomes (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)

  end of neo adjuvant chemotherapy

Secondary Outcomes (1)

• Recurrence-free survival and overall survival.

  every year

Study Arms (5)

HRD; 1x ddAC, 2x tCTC

EXPERIMENTAL

HRD 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.

Drug: Doxorubicin, cyclophosphamide, carboplatin, thiotepa, cyclophosphamide

HRD; 3x CP

ACTIVE COMPARATOR

HRD tumors; any response to 3x ddAC; 3 courses of CP

Drug: Carboplatin and Paclitaxel

non-HRD;3x CP

ACTIVE COMPARATOR

non-HRD tumors; unfavourable response to 3x ddAC; 3 courses of Carboplatin and Paclitaxel

Drug: Carboplatin and Paclitaxel

non-HRD; response; 3x ddAC

ACTIVE COMPARATOR

non-HRD tumors; favourable response to 3x ddAC; 3 more courses of ddAC

Drug: Doxorubicin, cyclophosphamide

non-HRD; response; 3x CP

ACTIVE COMPARATOR

non-HRD tumors; favourable response to 3x ddAC; 3 courses of Carboplatin and Paclitaxel

Drug: Carboplatin and Paclitaxel

Interventions

Carboplatin and Paclitaxel DRUG

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

Also known as: Carboplatin, Paclitaxel

HRD; 3x CP; non-HRD; response; 3x CP; non-HRD;3x CP

Doxorubicin, cyclophosphamide DRUG

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.

non-HRD; response; 3x ddAC

Doxorubicin, cyclophosphamide, carboplatin, thiotepa, cyclophosphamide DRUG

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.

HRD; 1x ddAC, 2x tCTC

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (14)

Medisch Centrum Alkmaar

Alkmaar, 1815 JD, Netherlands

Location

NKI-AVL

Amsterdam, 1066 CX, Netherlands

Location

OLVG

Amsterdam, 1090 HM, Netherlands

Location

Reinier de Graaf Groep

Delft, 2625 AD, Netherlands

Location

Deventer Ziekenhuis

Deventer, 7400 GC, Netherlands

Location

Albert Schweitzer ziekenhuis

Dordrecht, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, Netherlands

Location

Kennemer Gasthuis

Haarlem, 2000AK, Netherlands

Location

Atrium Medisch Centrum Parkstad

Heerlen, 6401 CX, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, 2130 AT, Netherlands

Location

LUMC

Leiden, 2300 RC, Netherlands

Location

Maasstad ziekenhuis

Rotterdam, 3007 AC, Netherlands

Location

Medisch Centrum Haaglanden

The Hague, 2501 CK, Netherlands

Location

Isala Klinieken

Zwolle, 8000 GK, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 19717533 BACKGROUND

• 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.

  PMID: 37689749 DERIVED

• 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.

  PMID: 27325334 DERIVED

• 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.

  PMID: 25937263 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Paclitaxel; AC protocol; Doxorubicin; Cyclophosphamide; Thiotepa

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sjoerd Rodenhuis, MD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2010
• First Posted: January 27, 2010
• Study Start: January 1, 2010
• Primary Completion: June 1, 2023
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 12, 2022

Record last verified: 2022-10

Locations

NL (14)