NordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC

NCT04335669 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: NBG-19-01; SWEBCG 19-01
• Study Type: interventional
• Target: 325
• Locations: 2 countries
• Sites: 24

Brief Summary

Primary aim: To compare the effect on pathologic complete response (pCR) rate of adding capecitabine to carboplatin based preoperative chemotherapy in early ER-negative and HER2-negative breast cancer. Pembrolizumab is allowed in both arms after approval for TNBC 2022.

Conditions

Breast Cancer; Triple Negative Breast Neoplasms

Keywords

Breast neoplasms; Triple negative breast neoplasms; Neoadjuvant treatment; Translational research; Pathologic response; Pathologic complete response; epirubicin; cyclophosphamide; paclitaxel; carboplatin; capecitabine; Survival outcomes; Homologous repair deficiency; pembrolizumab

Outcome Measures

Primary Outcomes (2)

• Pathological complete response rate.

  Rate of pathological complete response, allowing residual dcis, at surgery after preoperative chemotherapy.

  Immediately after surgery

• Primary translational outcome.

  Pathological complete response rate, allowing residual dcis, stratified for homologous repair deficiency.

  Immediately after surgery

Secondary Outcomes (6)

• Invasive Disease Free Survival (IDFS)

  Throughout the study, an average of 3 years

• Overall Survival (OS)

  Throughout the study, an average of 5 years

• Breast Cancer Specific Survival (BCSS)

  Throughout the study, an average of 3 years

• Distant Recurrence Free Survival (DRFS)

  Throughout the study, an average of 3 years

• Dose intensity

  Immediately after surgery

Other Outcomes (9)

• Subset characterization (histological subtypes)

  Immediately after surgery

• Subset characterization (germline mutations)

  Immediately after surgery

• Subset characterization (somatic mutations)

  Immediately after surgery

Study Arms (2)

Arm A (Platinum-based dose dense EC):

ACTIVE COMPARATOR

ddEC x 4 + pembrolizumab→ PK x 4 + pembrolizumab, Two-weekly epirubicin/cyclophosphamide (EC) x 4 (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2), followed after a three-week interval by three-weekly carboplatin x 4 (AUC = 5) together with weekly paclitaxel x 12 (80 mg/m2). Pembrolizumab is given as a 400 mg iv dosis every 6 weeks for the duration of preoperative chemotherapy.\*

Drug: epirubicin, cyclophosphamide, paclitaxel, carboplatin, pembrolizumab

Arm B (Platinum-based with capecitabine):

EXPERIMENTAL

CEX x 4→ PK x 4, Three-weekly cyclophosphamide/epirubicin/capecitabine (CEX) (epirubicin 75 mg/m2, cyclophosphamide 600 mg/m2 and capecitabine 900 mg/m2) x 4, followed after a three-week interval by three-weekly carboplatin x 4 (AUC = 5) together with weekly paclitaxel x 12 (80 mg/m2).Pembrolizumab is given as a 400 mg iv dosis every 6 weeks for the duration of preoperative chemotherapy.\* \*The addition of pembrolizumab is strongly recommended to all participating patients. However, patients with a documented contraindication, or unwilling to receive immunotherapy may be included in the study without the administration of pembrolizumab.

Drug: epirubicin, cyclophosphamide, capecitabine, paclitaxel, carboplatin, pembrolizumab

Interventions

epirubicin, cyclophosphamide, paclitaxel, carboplatin, pembrolizumab DRUG

Cytotoxic agents.

Also known as: anthracycline, taxane, platinum

Arm A (Platinum-based dose dense EC):

epirubicin, cyclophosphamide, capecitabine, paclitaxel, carboplatin, pembrolizumab DRUG

Cytotoxic agents.

Also known as: anthracycline, taxane, antimetabolite, platinum

Arm B (Platinum-based with capecitabine):

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent approved by the Ethical Review Board (IRB).
• Age ≥ 18 to \< 76 years.
• Histologically confirmed unilateral adenocarcinoma of the breast where neoadjuvant chemotherapy followed by definitive surgery is planned.
• Node positive disease (N1-3) or if clinically N0 Tumor size \>20 mm. When deciding T-stage the following hierarchy applies,
• MRI
• Ultrasound
• Mammography
• Clinical examination
• ER negative tumor defined by at least one the following:
• ER \< 1% cells positive by immunohistochemistry (IHC) or ER ≤ 10% cells positive by IHC and basal-like subtype using gene expression analysis
• ER \< 10% cells positive by IHC and PgR \< 10% cells positive by IHC
• HER2-normal tumor defined according to applicable national guidelines
• Consent for germline mutation screening for BRCA1, BRCA2 and other inherited breast cancer associated genes.
• WHO performance status 0 or 1.
• Negative pregnancy test in women of childbearing potential (premenopausal or \<12 months of amenorrhea post-menopause and who have not undergone surgical sterilization).

You may not qualify if:

• Clinical or radiological signs of metastatic disease.
• History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin cancer.
• Previous chemotherapy for cancer or other malignant disease.
• Charlson comorbidity index, excluding score for malignancy: (CCI) \> 2, Comment: In patients 70-75 a CCI = 3 is allowed, see appendix B.
• Inadequate organ function, suggested by the following laboratory results:
• a Absolute neutrophil count \< 1,5 x 109/L
• b Platelet count \< 100 x 109/L
• c Hemoglobin \< 90 g/L
• d Total bilirubin greater than the upper limit of normal (ULN) unless the patient has documented Gilbert´s syndrome
• e ASAT (SGOT) and/or ALAT (SGPT) \> 2,5 x ULN
• f ASAT (SGOT) and/or ALAT (SGPT) \> 1,5 x ULN with concurrent serum alkaline phosphatase (ALP) \> 2,5 x ULN
• g Serum creatinine clearance \< 50 ml/min
• Concurrent peripheral neuropathy of grade 3 or greater (NCI-CTCAE, Version 5.0).
• Patient who is actively breast feeding.
• Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

Sponsors & Collaborators

• Lund University Hospital: lead
• Swedish Breast Cancer Group: collaborator
• Danish Breast Cancer Cooperative Group: collaborator

Study Sites (24)

Vejle Hospital

Vejle, Region Syd, 7100, Denmark

Location

Aalborg Universitetshospita

Aalborg, 9000, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Sydvestjysk Sygehus

Esbjerg, 6700, Denmark

Location

Nordsjællands Hospital

Hillerød, 3400, Denmark

Location

Regionsjælland Næstved Sygehus

Næstved, 4700, Denmark

Location

Sønderborg sygehus

Sønderborg, 6300, Denmark

Location

Vejle syghus

Vejle, 7100, Denmark

Location

Centralsjukhuset i Kristianstad

Kristianstad, Skåne County, 291 85, Sweden

Location

Södra Älvsborgs Hospital

Borås, 501 82, Sweden

Location

Gävle hospital, Department of Oncology

Gävle, 803 24, Sweden

Location

Sahlgrenska University Hospital, Department of Oncology

Gothenburg, 413 46, Sweden

Location

Halmstad Hospital, Department of Surgery

Halmstad, 302 33, Sweden

Location

Ryhov Hospital

Jönköping, 551 85, Sweden

Location

Karlstad Hospital

Karlstad, 652 30, Sweden

Location

Skåne University Hospital, Department of Oncology

Malmo, 20501, Sweden

Location

Örebro University Hospital, Department of Oncology

Örebro, 701 85, Sweden

Location

Capio S:t Göran Hospital, Department of Oncology

Stockholm, 112 19, Sweden

Location

Södersjukhuset, Department of Oncology

Stockholm, 118 61, Sweden

Location

Sundsvall hospital

Sundsvall, 851 86, Sweden

Location

Norrland University Hospital, Department of Oncology

Umeå, 907 37, Sweden

Location

Academical Hospital, Department of Oncology

Uppsala, 753 09, Sweden

Location

Växjö Hospital, Department of Oncology

Vaxjo, 352 34, Sweden

Location

Västmanlands Hopsital Västerås

Västerås, 721 89, Sweden

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms; Pathologic Complete Response

Interventions

Epirubicin; Cyclophosphamide; Paclitaxel; Carboplatin; pembrolizumab; Anthracyclines; taxane; Platinum; Capecitabine; Antimetabolites

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Coordination Complexes; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Noxae; Toxic Actions

Study Officials

• Niklas Loman, MD, PhD

  Lund University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: April 6, 2020
• Study Start: December 20, 2019
• Primary Completion (Estimated): September 1, 2035
• Study Completion (Estimated): September 1, 2035
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (8); SE (16)