Neoadjuvant Response-guided Treatment of Luminal B-type Tumors and Luminal A-type Tumors With Node Metastases

NCT02603679 | Active Not Recruiting Phase 2

• 1 other identifier: PREDIX LumB
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Early-Stage Breast Carcinoma; Estrogen Receptor Positive Tumor

Keywords

Cyclin-Dependent Kinase Inhibitor p16

Outcome Measures

Primary Outcomes (1)

• Radiological Objective Response Rate after Completion of the First 12-week Period of Primary Medical 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

Secondary Outcomes (12)

• Pathological Objective Response Rate

  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

  From start of treatment until termination of the preoperative treatment after 24 weeks

• Disease-Free Survival

  From date of surgery until 10 years past surgery

• Breast Cancer-Specific Survival

  From date of surgery until 10 years past surgery

• Overall Survival

  From date of surgery until 10 years past surgery

Study Arms (4)

A: Weekly Paclitaxel

ACTIVE COMPARATOR

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

Drug: Paclitaxel

B: Tamoxifen + Palbociclib

EXPERIMENTAL

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.

Drug: Tamoxifen + Palbociclib

B: Aromatase Inhibitor + Palbociclib

EXPERIMENTAL

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.

Drug: Aromatase Inhibitor + Palbociclib

B: Goserelin + Aromatase Inhibitor + Palbociclib

EXPERIMENTAL

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.

Drug: Goserelin + Aromatase Inhibitor + Palbociclib

Interventions

Paclitaxel DRUG

Any brand of paclitaxel may be used, excluding nab-paclitaxel

A: Weekly Paclitaxel

Tamoxifen + Palbociclib DRUG

Any brand of tamoxifen may be used

Also known as: Tamoxifen, Ibrance

B: Tamoxifen + Palbociclib

Aromatase Inhibitor + Palbociclib DRUG

Any brand of letrozole, anastrozole or exemestane may be used

Also known as: Letrozole, Anastrozole, Exemestane, Ibrance

B: Aromatase Inhibitor + Palbociclib

Goserelin + Aromatase Inhibitor + Palbociclib DRUG

Any brand of letrozole, anastrozole or exemestane may be used

Also known as: Zoladex, Letrozole, Anastrozole, Exemestane, Ibrance

B: Goserelin + Aromatase Inhibitor + Palbociclib

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Female or male patients with breast cancer confirmed by histology
• 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
• Age 18 years or older. Elderly patients in condition adequate for planned therapy
• Primary breast cancer \>20mm in diameter and/or verified regional lymph node metastases
• Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders
• LVEF \>55%
• ECOG performance status 0-1
• 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

You may not qualify if:

• Distant metastases, including node metastases in the contralateral thoracic region or in the mediastinum
• 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
• Patients in child-bearing age without adequate contraception
• Pregnancy or lactation
• Uncontrolled hypertension, heart, liver, kidney related or other medical or psychiatric disorders

Sponsors & Collaborators

• Thomas Hatschek: lead

Study Sites (3)

Södersjukhuset

Stockholm, 11883, Sweden

Location

Karolinska University Hospital

Stockholm, 17176, Sweden

Location

Capio S:t Göran Hospital

Stockholm, Sweden

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Tamoxifen; palbociclib; Aromatase Inhibitors; Letrozole; Anastrozole; exemestane; Goserelin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Thomas Hatschek, Assoc Prof

  Breast-Sarcoma Unit, Dept. of Oncology, Karolinska University Hospital

  STUDY CHAIR

• Jonas Bergh, Professor

  Dept. of Oncology-Pathology, Karolinska Institutet

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sen. Consultant, MD, PhD, Assoc. professor

Study Record Dates

• First Submitted: November 4, 2015
• First Posted: November 13, 2015
• Study Start: February 1, 2015
• Primary Completion: July 30, 2021
• Study Completion (Estimated): December 31, 2031
• Last Updated: August 3, 2021

Record last verified: 2021-07

Locations

SE (3)