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

30 de julio de 2021 actualizado por: 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.

Descripción general del estudio

Estado

Activo, no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

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 de estudio

Intervencionista

Inscripción (Actual)

181

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Suecia
      • Stockholm, Suecia, 17176
        • Karolinska University Hospital
      • Stockholm, Suecia, 11883
        • Södersjukhuset
      • Stockholm, Suecia
        • Capio S:t Göran Hospital

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: 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
Experimental: 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
Otros nombres:
  • Ibrance
  • Tamoxifeno
Experimental: 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
Otros nombres:
  • Ibrance
  • Exemestano
  • Letrozol
  • Anastrozol
Experimental: 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
Otros nombres:
  • Zoladex
  • Ibrance
  • Exemestano
  • Letrozol
  • Anastrozol

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Radiological Objective Response Rate after Completion of the First 12-week Period of Primary Medical Treatment
Periodo de tiempo: 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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Pathological Objective Response Rate
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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]
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Thomas Hatschek

Investigadores

  • Silla de estudio: Thomas Hatschek, Assoc Prof, Breast-sarcoma Unit, Dept. of Oncology, Karolinska University Hospital
  • Director de estudio: Jonas Bergh, Professor, Dept. of Oncology-Pathology, Karolinska Institutet

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

1 de febrero de 2015

Finalización primaria (Actual)

30 de julio de 2021

Finalización del estudio (Anticipado)

31 de diciembre de 2031

Fechas de registro del estudio

Enviado por primera vez

4 de noviembre de 2015

Primero enviado que cumplió con los criterios de control de calidad

10 de noviembre de 2015

Publicado por primera vez (Estimar)

13 de noviembre de 2015

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

3 de agosto de 2021

Última actualización enviada que cumplió con los criterios de control de calidad

30 de julio de 2021

Última verificación

1 de julio de 2021

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • PREDIX LumB

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

producto fabricado y exportado desde los EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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