Palbociclib Plus Fulvestrant in Women With Hormone Receptor Positive and Human Epidermal Growth Factor Receptor Type 2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination With Hormonal Therapy

NCT04318223 | Unknown Phase 2

• 1 other identifier: GIM24-PALBO-BP
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 19

Brief Summary

The aim of the present study is to evaluate the efficacy and safety of palbociclib plus fulvestrant after failure of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) plus a CDK4/6 inhibitor, in women with HR+ and HER2- LABC or MBC. Primary endpoint:

• For patients with measurable disease at baseline, progression will be determined according to the RECIST criteria v1.1.
• In the absence of measurable disease at baseline, patients with bone only lesions, lytic or mixed (lytic + sclerotic), will be allowed to enter the study and the following will be considered disease progression among these patients:
• The appearance of one or more new lytic lesions in bone,
• The appearance of one or more new lesions outside of bone,
• Unequivocal progression of existing bone lesions. Note: Pathologic fracture, new compression fracture, or complications of bone metastases will not be considered as evidence of disease progression, unless one of the above-mentioned criteria is fulfilled.
• To assess the Quality of Life (QoL) of patients receiving the combination treatment palbociclib plus fulvestrant at progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and a CDK4/6 inhibitor.
• To evaluate the efficacy of the combination of fulvestrant plus palbociclib at the progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and CDK4/6 inhibitors with respect to:
• Overall response rate (ORR)
• Progression Free Survival (PFS)
• Overall Survival (OS)
• Safety and tolerability
• To assess predictive biomarkers of response/resistance to fulvestrant plus palbociclib using metastatic tumor tissue samples and liquid biopsies.

Conditions

Metastatic Breast Cancer; Locally Advanced Breast Cancer

Keywords

hormone receptor positive; human epidermal growth factor receptor type 2 negative

Outcome Measures

Primary Outcomes (2)

• Clinical Benefit Response (CBR)

  To assess the clinical benefit rate (CBR) of the treatment, the Clinical Benefit Response (CBR) is defined as complete response (CR) or partial response (PR) or stable disease (SD) \>24 weeks according to the RECIST version 1.1 recorded in the time period between enrollment and disease progression or death of any cause. CBR with the corresponding 95% Confidence Interval (95% C.I.) will be estimated using the exact binomial method. A Simon optimal two-stage design will be used to exclude a clinical benefit rate (CBR) of 30% (p0 = 0.30) with a clinical relevant target of 40% (p1 = 0.40) using a one-sided alpha-level of 0.05 and a power of 0.80. Fifty-nine (59) subjects will be enrolled in the first phase. If nineteen (19) of fewer CR+PR+SD will be observed, the study will be terminated. Otherwise the treatment will be considered worthy of further investigation and 109 more subjects will be enrolled for a total sample size of 168 subjects.

  About 48 months

• Patient Reported Outcomes (PRO)

  Breast cancer-specific quality of life total scale scores and single item scale scores will be summarized by descriptive summary tables at baseline and over time. The mean changes from baseline will also be summarized using descriptive statistics. Longitudinal trajectories of total scale scores will be modelled using linear mixed models with random intercept to account for subject specific baseline assessment; time will be modeled continuously using days since baseline; potential non linear trend will be examined by adding quadratic terms to the model. Selection of the best model will be based on Akaike Information Criterion (AIC).

  About 48 months

Secondary Outcomes (4)

• Efficacy of the combination of fulvestrant plus palbociclib

  About 48 months

• Efficacy of the combination of fulvestrant plus palbociclib

  About 48 months

• Efficacy of the combination of fulvestrant plus palbociclib

  About 48 months

• Predictive biomarkers of response/resistance

  About 48 months

Study Arms (1)

single-arm study following a Simon's two-stage optimal design

EXPERIMENTAL

Single-arm study with the primary objective of assessing the efficacy and safety of palbociclib in combination with fulvestrant (Faslodex) in women with HR+, HER2-negative metastatic breast cancer, regardless of their menopausal status, whose disease has progressed after prior treatment with AI plus a CDK4/6 inhibitor.

Drug: Palbociclib

Interventions

Palbociclib DRUG

Patients will be enrolled into the study and assign to receive Palbociclib 125 mg/day orally for 3 weeks followed by 1 week off plus fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, every 28 days (+/- 7 days) thereafter starting from Day 1 of Cycle 1

single-arm study following a Simon's two-stage optimal design

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult (≥ 18 years of age) pre or post-menopausal women with LABC or MBC not amenable to curative treatment by surgery or radiotherapy, progressing to a CDK4/6 inhibitor in combination with aromatase inhibitor or tamoxifen in the adjuvant or metastatic setting. To be enrolled in the present trial patients must have relapsed at least after 12 months from the last CDK4/6 dosage in the adjuvant setting or at progression from a first line combined hormonal treatment for metastatic disease with a CDK4/6 inhibitor plus AI or Tam with duration of, at least, 6 months. For metastatic disease, patients must have achieved, at least a stable disease while the first line hormonal treatment with a CDK4/6 inhibitor plus AI or Tam to be enrolled in the trial.
• Patients receiving up to one line of chemotherapy before the first line hormonal treatment with a CDK4/6 inhibitor for metastatic disease may be enrolled in the study.
• Histological confirmation of ER and/or PgR ≥ 1% and HER2 negative breast cancer (IHC status 0, 1+, 2+ and FISH not amplified).
• Premenopausal women: in order to be eligible must have achieved surgical menopause with bilateral oophorectomy or ovarian radiation or medical menopause by treatment with a luteinizing hormone-releasing hormone (LHRH) agonist (LHRHa) for induction of ovarian suppression.
• Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment.
• Patients who received ≤ 28 days of fulvestrant for second line advanced breast cancer treatment prior to study enrollment are eligible.
• Patients must have:
• At least one lesion that can be accurately measured in at least one dimension ≥ 20 mm with conventional imaging techniques or ≥ 10 mm with spiral CT or MRI
• Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
• Adequate bone marrow and coagulation and adequate organ function defined as follows:
• ANC \> 1,000/mm3 (1.0 x 109/L);
• Platelets \> 75,000/mm3 (75 x 109/L);
• Hemoglobin≥ 9 g/dL (90 g/L);
• Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 60 ml/min as calculated using the method standard for the institution;
• Total serum bilirubin≤1.5 x ULN (\<2.5 ULN if Gilbert's disease);

You may not qualify if:

• HER2-overexpressing patients by local laboratory testing (IHC3+ staining or in situ hybridization positive).
• Patients who received \> 1 line of chemotherapy as treatment for MBC.
• Patients who received \> 1 line of a CDK4/6 inhibitor in combination with hormonal treatment for LABC or MBC or who have relapsed at less than 12 months from the end of adjuvant treatment with a CDK4/6 inhibitor. For metastatic disease, patients with a progressive disease within the first 6 months of treatment while on first line therapy with a CDK4/6 inhibitor, will be excluded.
• Patients receiving chemotherapy or any type of hormonal therapy after treatment with a CDK4/6 inhibitor for metastatic disease.
• Patients interrupting the previous treatment with CDK4/6 inhibitor for cardiac and/or hepatic toxicity and not for disease progression.
• Pregnant, lactating women.
• Known hypersensitivity to CDK4/6 inhibitors, fulvestrant, or to any of the excipients.
• Radiotherapy within four weeks prior to enrollment (baseline/treatment start) except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment (baseline/treatment start). Patients must have recovered from radiotherapy toxicities prior to enrollment.
• Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
• short duration (\<2 weeks) of systemic corticosteroids is allowed (e.g., chronic obstructive pulmonary disease, anti-emetic);
• low doses of corticosteroids for brain metastasis treatment is allowed.
• Patients with symptomatic visceral disease in need of urgent disease control (e.g., significant dyspnea related to pulmonary lymphangitic carcinomatosis and lung metastases or clinically meaningful symptomatic liver metastasis at the judgement of treating investigator).
• Symptomatic brain metastases.
• Patients with a known history of HIV seropositivity.

Sponsors & Collaborators

• Consorzio Oncotech: lead

Study Sites (19)

Nuovo ospedale di Prato - S. Stefano

Prato, Firenze, 59100, Italy

NOT YET RECRUITING

Ospedale Civile S. Giovanni di Dio

Frattamaggiore, Napoli, 80027, Italy

NOT YET RECRUITING

Centro di Riferimento oncologico

Aviano, Pordenone, 33081, Italy

NOT YET RECRUITING

Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, 10060, Italy

NOT YET RECRUITING

Ospedale Sacro Cuore di Gesù Fatebenefratelli

Benevento, 82100, Italy

NOT YET RECRUITING

A.O. Osp. Riuniti - ASST PAPA GIOVANNI 23

Bergamo, 24127, Italy

NOT YET RECRUITING

Ospedale di Brindisi "Perrino"

Brindisi, 72100, Italy

NOT YET RECRUITING

Ospedale Policnico San Martino

Genova, 16132, Italy

NOT YET RECRUITING

Ospedale Vito Fazzi

Lecce, 73100, Italy

NOT YET RECRUITING

Azienda Ospedaliera Papardo

Messina, 98158, Italy

RECRUITING

Azienda Ospedaliero - Universitaria di Modena

Modena, 41125, Italy

NOT YET RECRUITING

A.O.U. Seconda Universita' degli Studi di Napoli

Napoli, 80131, Italy

RECRUITING

Azienda Ospedaliera 'A. CARDARELLI'

Napoli, 80131, Italy

NOT YET RECRUITING

Azienda Ospedaliera dei Colli - P.Monaldi

Napoli, 80131, Italy

RECRUITING

Istituto Nazionale Tumori IRCCS Pascale

Napoli, 80131, Italy

NOT YET RECRUITING

Università degli Studi di Napoli "Federico II"

Napoli, 80131, Italy

RECRUITING

A.O.U. Pisana

Pisa, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori Regina Elena (IRE

Roma, 00144, Italy

RECRUITING

Ospedale Sandro Pertini

Roma, 00157, Italy

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib

Condition Hierarchy (Ancestors)

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

Study Officials

• Carmine De Angelis, MD

  Federico II University

  STUDY DIRECTOR

Central Study Contacts

Grazia Arpino, MD

CONTACT

+390817463772; grazia.arpino@unina.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase II, multicentre, single-arm study following a Simon's two-stage optimal design

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: March 23, 2020
• Study Start: July 16, 2019
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: March 23, 2020

Record last verified: 2020-03

Locations

IT (19)