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

NCT ID: NCT02603679

Last Updated: 2021-08-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2031-12-31

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.

Detailed Description

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.

Conditions

Early-Stage Breast Carcinoma; Estrogen Receptor Positive Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Tamoxifen + Palbociclib

Intervention Type: DRUG

Any brand of tamoxifen may be used

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.

Group Type: EXPERIMENTAL

Aromatase Inhibitor + Palbociclib

Intervention Type: DRUG

Any brand of letrozole, anastrozole or exemestane may be used

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.

Group Type: EXPERIMENTAL

Goserelin + Aromatase Inhibitor + Palbociclib

Intervention Type: DRUG

Any brand of letrozole, anastrozole or exemestane may be used

Interventions

Paclitaxel

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

Intervention Type: DRUG

Tamoxifen + Palbociclib

Any brand of tamoxifen may be used

Intervention Type: DRUG

Aromatase Inhibitor + Palbociclib

Any brand of letrozole, anastrozole or exemestane may be used

Intervention Type: DRUG

Goserelin + Aromatase Inhibitor + Palbociclib

Any brand of letrozole, anastrozole or exemestane may be used

Intervention Type: DRUG

Other Intervention Names

Tamoxifen; Ibrance; Letrozole; Anastrozole; Exemestane; Ibrance; Zoladex; Letrozole; Anastrozole; Exemestane; Ibrance

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thomas Hatschek

OTHER

Sponsor Role: lead

Responsible Party

Thomas Hatschek

Sen. Consultant, MD, PhD, Assoc. professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Thomas Hatschek, Assoc Prof

Role: STUDY_CHAIR

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

Jonas Bergh, Professor

Role: STUDY_DIRECTOR

Dept. of Oncology-Pathology, Karolinska Institutet

Locations

Södersjukhuset

Stockholm, , Sweden

Karolinska University Hospital

Stockholm, , Sweden

Capio S:t Göran Hospital

Stockholm, , Sweden

Countries

Sweden

Other Identifiers

PREDIX LumB

Identifier Type: -

Identifier Source: org_study_id