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Neoadjuvant Response-guided Treatment of Luminal B-type Tumors and Luminal A-type Tumors With Node Metastases (PREDIX LumB)

30 luglio 2021 aggiornato da: Thomas Hatschek

PREDIX Luminal B - Neoadjuvant Response-guided Treatment of ER Positive Tumors With High Proliferation or Low Proliferation With Metastatic Nodes. Part of a Platform of Translational Phase II Trials Based on Molecular Subtypes

The purpose of this neoadjuvant trial is to evaluate efficacy and toxicity of chemotherapy using weekly paclitaxel (arm A) versus the combination of the cdk 4/6 inhibitor palbociclib and standard endocrine treatment (arm B). After 12 weeks treatment is switched crossover. During the 24-weekly treatment period, clinical and radiological evaluations are performed repeatedly. Switch between the treatment arms A and B is allowed in case of lack of response or due to toxicity. A translational subprotocol is a mandatory part of the study protocol, except for use of PET-CT evaluations. Postoperatively, patients receive three 3-weekly courses of chemotherapy with a combination of epirubicin and cyclophosphamide.

Panoramica dello studio

Stato

Attivo, non reclutante

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Patients are randomized to either weekly treatment with paclitaxel (arm A) or endocrine treatment in combination with palbociclib (arm B) for 12 weeks. Choice of endocrine treatment is for pre- and perimenopausal women and all men tamoxifen 20 mg daily, alternatively for women in this age cohort, an LHRH analogue in combination with an aromatase inhibitor, for all postmenopausal women treatment with an aromatase inhibitor. The aromatase inhibitors to be used according to local practice are anastrozole 1 mg daily, exemestane 25 mg daily, or letrozole 2.5 mg daily. Pre- or perimenopausal women and all men are treated with tamoxifen, alternatively with an LHRH analogue in combination with an aromatase inhibitor (only women). Postmenopausal women receive an aromatase inhibitor.

After 12 weeks, patients without signs of disease progression (PD) are switched to either endocrine treatment in combination with palbociclib (arm A) or weekly treatment with paclitaxel (arm B) for 12 weeks. Postoperatively, patients receive three 3-weekly courses of chemotherapy with a combination of epirubicin and cyclophosphamide.

Before start, after 6, 12, 18 and 24 weeks of treatment, radiological assessments of tumor size are performed using mammography and ultrasound alt. MRI breast; PET-CT, confined to the breast and regional lymph nodes, before start, after 12 and 24 weeks, blood tests before start, after 1 week, 12, 18 and 24 weeks. Physical examinations are performed before start and then four-weekly after weeks 4, 8, 12, 16, 20 and 24 weeks of treatment.

In case of disease progression during ongoing study treatment, individualized management in the patient's best interest must be considered, in which case surgery is the primary option.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

181

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Svezia
      • Stockholm, Svezia, 17176
        • Karolinska University Hospital
      • Stockholm, Svezia, 11883
        • Sodersjukhuset
      • Stockholm, Svezia
        • Capio S:t Göran Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  1. Written informed consent
  2. Female or male patients with breast cancer confirmed by histology
  3. Tumor and blood samples available. Luminal B type confirmed by immunohistochemistry or, preferably, genomic profiling using Next-Generation Sequencingwith ER ≥120% and Ki67 ≥20% and not HER2 amplified, or, if aged 40 or younger and/or verified lymph node metastases, luminal A type, defined as ER and PR positive ≥20% and the proliferation marker Ki 67 <20% and not HER2 amplified. Any luminal B, Luminal A with verified lymph node metastases and/or aged 40 or younger
  4. Age 18 years or older. Elderly patients in condition adequate for planned therapy
  5. Primary breast cancer >20mm in diameter and/or verified regional lymph node metastases
  6. Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders
  7. LVEF >55%
  8. ECOG performance status 0-1
  9. Primary breast cancer as defined in p. 5 plus at most 2 morphologically characterized well-defined distant metastases accessible for stereotactic radiotherapy, provided that this treatment is available

Exclusion Criteria:

  1. Distant metastases, including node metastases in the contralateral thoracic region or in the mediastinum
  2. Other malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix
  3. Patients in child-bearing age without adequate contraception
  4. Pregnancy or lactation
  5. Uncontrolled hypertension, heart, liver, kidney related or other medical or psychiatric disorders

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: A: Weekly Paclitaxel
Patients receive weekly paclitaxel 80mg/m2, eventually dose-adjusted in relation to side effects, for a 12-week period. Thereafter, treatment is switched to endocrine treatment in combination with palbociclib. Pre- or perimenopausal women and all men are treated with tamoxifen, alternatively with an LHRH analogue in combination with an aromatase inhibitor (only women); postmenopausal women receive an aromatase inhibitor together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period, repeated twice during the second 12-week period
Droga: Paclitaxel
Any brand of paclitaxel may be used, excluding nab-paclitaxel
Sperimentale: B: Tamoxifen + Palbociclib
Pre- or perimenopausal women and all men are treated with tamoxifen together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period, repeated twice during a 12-week period. Thereafter, treatment is switched to weekly paclitaxel 80mg/m2, eventually dose-adjusted in relation to side effects, for further 12 weeks.
Droga: Tamoxifen + Palbociclib
Any brand of tamoxifen may be used
Altri nomi:
  • Ibrance
  • Tamoxifene
Sperimentale: B: Aromatase Inhibitor + Palbociclib
Postmenopausal women receive an aromatase inhibitor together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period, repeated twice during a 12-week period. Thereafter, treatment is switched to weekly paclitaxel 80mg/m2, eventually dose-adjusted in relation to side effects, for further 12 weeks.
Droga: Aromatase Inhibitor + Palbociclib
Any brand of letrozole, anastrozole or exemestane may be used
Altri nomi:
  • Ibrance
  • Exemestane
  • Letrozolo
  • Anastrozolo
Sperimentale: B: Goserelin + Aromatase Inhibitor + Palbociclib
Pre- or perimenopausal women may be treated with goserelin and an aromatase inhibitor together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period, repeated twice during a 12-week period. Thereafter, treatment is switched to weekly paclitaxel 80mg/m2, eventually dose-adjusted in relation to side effects, for further 12 weeks.
Droga: Goserelin + Aromatase Inhibitor + Palbociclib
Any brand of letrozole, anastrozole or exemestane may be used
Altri nomi:
  • Zoladex
  • Ibrance
  • Exemestane
  • Letrozolo
  • Anastrozolo

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Radiological Objective Response Rate after Completion of the First 12-week Period of Primary Medical Treatment
Lasso di tempo: Start of treatment until 12 weeks of treatment
Radiological response by use of mammography and ultrasound, alternatively MRI of the breast, if mammography/ultrasound does not allow for objective measurements of the primary tumor. Clinical measurements using calliper, if the tumor is palpable and tumor size cannot be estimated by radiological methods
Start of treatment until 12 weeks of treatment

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Pathological Objective Response Rate
Lasso di tempo: From the date of surgery up to 4 weeks after surgery
Presence/abscense of residual tumor in mm, fibrosis and other signs of response by histology
From the date of surgery up to 4 weeks after surgery
Sequencing of Chemotherapy versus Endocrine Treatment plus Palbociclib in relation to Radiological Objective Response Rate after Completion of the 24-week Period of Primary Medical Treatment
Lasso di tempo: From start of treatment until termination of the preoperative treatment after 24 weeks
Radiological response by use of mammography and ultrasound, alternatively MRI of the breast, if mammography/ultrasound does not allow for objective measurements of the primary tumor. Clinical measurements using calliper, if the tumor is palpable and tumor size cannot be estimated by radiological methods
From start of treatment until termination of the preoperative treatment after 24 weeks
Disease-Free Survival
Lasso di tempo: From date of surgery until 10 years past surgery
Disease-free survival includes all events related to breast cancer, and death from any cause during the follow-up period
From date of surgery until 10 years past surgery
Breast Cancer-Specific Survival
Lasso di tempo: From date of surgery until 10 years past surgery
Breast cancer-specific survival includes all events related to breast cancer and death caused by breast cancer during the follow-up period
From date of surgery until 10 years past surgery
Overall Survival
Lasso di tempo: From date of surgery until 10 years past surgery
Overall survival relates to death from any cause during the follow-up period
From date of surgery until 10 years past surgery
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Lasso di tempo: From start of treatment until 28 days after termination of 24 weeks of treatment. Delayed toxicity is reported until 60 months follow-up
Safety will be assessed using NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE) for reporting laboratory and non-laboratory toxicities
From start of treatment until 28 days after termination of 24 weeks of treatment. Delayed toxicity is reported until 60 months follow-up
Health-Related Quality of Life
Lasso di tempo: From start of study treatment until termination after 24 weeks, and then annually during 5 years of postoperative follow-up period
From start of study treatment until termination after 24 weeks, and then annually during 5 years of postoperative follow-up period
Frequency of Breast-Conserving Surgery
Lasso di tempo: At surgery after neoadjuvant therapy
Refers to the rate of patients who are operated with breast-conserving surgery compared with mastectomy
At surgery after neoadjuvant therapy
Characteristics of the Genome of Previously Untreated Tumors Before and After Exposition to Treatment
Lasso di tempo: Before start and during treatment, at surgery, and then annually during the 60 months of postoperative follow-up period
New Generation Sequencing (NGS) is performed on biopsies from the tumors with the aim to classify the tumors according to PAM50. Repeated analyses of tumor tissue during the treatment process will be performed to identify heterogeneity and mutations which might be responsible for resistance to study treatment. Blood samples are collected to identify tumor DNA sequences which might predict recurrence during the follow-up period. Tissue and blood samples are also analyzed in case of recurrence. The results are descriptive and expressed as clustering. Units of measure are lacking
Before start and during treatment, at surgery, and then annually during the 60 months of postoperative follow-up period
Changes of the Proteome of Previously Untreated Tumors Before and After Exposition to Treatment
Lasso di tempo: Before start, during treatment and at surgery
Proteome analyses with the intention to identify tumor-specific pathways are performed on repeated biopsies from the tumors. The results are descriptive, defined units of measure are lacking
Before start, during treatment and at surgery
Quantification of Hormone Receptors Before and After Treatment
Lasso di tempo: Before start, during treatment and at surgery
Immunohistochemistry on core biopsies before start, after 10 weeks of treatment, and tumor samples from the surgical specimen. Presence of estrogen receptor (ER) and progesterone receptor (PR), described as percentage in relation to the total count of tumor cells
Before start, during treatment and at surgery
Quantification of Proliferation Before and After Treatment
Lasso di tempo: Before start, during treatment and at surgery
Immunohistochemistry on core biopsies before start, after 10 weeks of treatment, and tumor samples from the surgical specimen. Presence of cells indicating proliferation by use of Ki67, described as percentage in relation to the total count of tumor cells
Before start, during treatment and at surgery

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Thomas Hatschek

Investigatori

  • Cattedra di studio: Thomas Hatschek, Assoc Prof, Breast-sarcoma Unit, Dept. of Oncology, Karolinska University Hospital
  • Direttore dello studio: Jonas Bergh, Professor, Dept. of Oncology-Pathology, Karolinska Institutet

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

1 febbraio 2015

Completamento primario (Effettivo)

30 luglio 2021

Completamento dello studio (Anticipato)

31 dicembre 2031

Date di iscrizione allo studio

Primo inviato

4 novembre 2015

Primo inviato che soddisfa i criteri di controllo qualità

10 novembre 2015

Primo Inserito (Stima)

13 novembre 2015

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

3 agosto 2021

Ultimo aggiornamento inviato che soddisfa i criteri QC

30 luglio 2021

Ultimo verificato

1 luglio 2021

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • PREDIX LumB

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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Malattie rare

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