Neoadjuvant Response-guided Treatment of Slowly Proliferating Hormone Receptor Positive Tumors

NCT02592083 | Active Not Recruiting Phase 2

• 1 other identifier: PREDIX LumA
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this neoadjuvant trial is to evaluate efficacy and toxicity of the cdk 4/6 inhibitor palbociclib when added to standard endocrine treatment. Initially, patients receive endocrine treatment for 4 weeks. In case of decrease of proliferation (Ki67) patients are then randomized between either continuous endocrine therapy (arm A) or the same treatment with addition of palbociclib (arm B). Patients with no change of proliferation are allocated to endocrine treatment + palbociclib without randomization (arm C). During the 12-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.

Conditions

Early-Stage Breast Carcinoma; Hormone Receptor Positive Tumor

Keywords

Neoadjuvant Therapy; Cyclin-Dependent Kinase Inhibitor p16

Outcome Measures

Primary Outcomes (1)

• Clinical and Radiological Response

  Clinical evaluations by use of calliper, radiological evaluations with mammography and ultrasound after 4, 10 and 16 weeks, PET-CT after 10 weeks of treatment, compared with baseline measurements

  After 16 weeks of preoperative treatment

Secondary Outcomes (10)

• Pathological Evaluation of Tumor Response

  From date of surgery up to 4 weeks

• Disease-free Survival

  From date of surgery until 60 months past surgery

• Breast Cancer-specific Survival

  From date of surgery until 60 months past surgery

• Overall Survival

  From date of surgery until 60 months past surgery

• Incidence of treatment-emergent adverse events [Safety and Tolerability]

  From start of treatment until 28 days after termination of treatment. Delayed toxicity is reported until 60 months follow-up

Study Arms (3)

A: Endocrine treatment

ACTIVE COMPARATOR

Pre- or perimenopausal women are treated with tamoxifen, alternatively with an LHRH analogue in combination with an aromatase inhibitor (only women); postmenopausal women receive an aromatase inhibitor. The preoperative treatment is continued for further 12 weeks, provided that re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option

Drug: Tamoxifen or Aromatase Inhibitor or Aromatase Inhibitor + goserelin

B: Endocrine treatment + palbociclib

EXPERIMENTAL

Patients receive the same endocrine treatment as in arm A together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period. The combined treatment is continued for further 12 weeks, provided that re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option

Drug: Tamoxifen or Aromatase Inhibitor or Aromatase Inhibitor + goserelin; Drug: Palbociclib

C: Endocrine treatment + palbociclib

EXPERIMENTAL

Patients receive the same endocrine treatment as in arm A together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period. The combined treatment is continued for further 12 weeks, if re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option

Drug: Tamoxifen or Aromatase Inhibitor or Aromatase Inhibitor + goserelin; Drug: Palbociclib

Interventions

Tamoxifen or Aromatase Inhibitor or Aromatase Inhibitor + goserelin DRUG

Also known as: Tamoxifen, Letrozol or Anastrozol or Exemestane, Zoladex

A: Endocrine treatment; B: Endocrine treatment + palbociclib; C: Endocrine treatment + palbociclib

Palbociclib DRUG

Also known as: Ibrance

B: Endocrine treatment + palbociclib; C: Endocrine treatment + palbociclib

Eligibility Criteria

• Age: 41 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Female patients with non-lobular breast cancer confirmed by histology
• Tumor and blood samples available. Luminal A type confirmed by immunohistochemistry with ER and PR positive ≥50% and the proliferation marker Ki 67 \<20% and not HER2 amplified
• Age older than 40 years
• Primary breast cancer \>20mm without lymph node metastases
• Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders
• LVEF \>50%
• ECOG performance status 0-1

You may not qualify if:

• Metastases, including node metastases in the ipsilateral and/or 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
• Age ≤40 years
• Lobular carcinoma
• Patients in child-bearing age without adequate contraception
• Pregnancy or lactation
• Severe medical or psychiatric disorders where the study treatment or study procedures carry increased risk of deterioration of health status

Sponsors & Collaborators

• Thomas Hatschek: lead

Study Sites (1)

Department of Oncology, Karolinska University Hospital

Stockholm, 17176, Sweden

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; 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; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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: October 26, 2015
• First Posted: October 30, 2015
• Study Start: October 1, 2015
• Primary Completion: February 1, 2019
• Study Completion (Estimated): February 1, 2029
• Last Updated: July 7, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)