To Reverse ENDocrine Resistance Trial - PD 0332991 Monotherapy vs PD 0332991 in Combination With the Endocrine Therapy

NCT02549430 | Completed Phase 2

• 2 other identifiers: TREnd2011-005637-38
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 6

Brief Summary

This study aims to assess the activity of PD0332991 in monotherapy and in combination with the endocrine therapy (anastrozole, letrozole, exemestane or fulvestrant) on which the patient has progressed in the previous line for advanced breast cancer in order to reverse endocrine resistance.

Conditions

Breast Cancer

Keywords

Advanced breast cancer; Postmenopausal; ER positive; Her2 negative

Outcome Measures

Primary Outcomes (1)

• Incidence of complete response (CR), partial response (PR) or stable disease (SD) ≥24 weeks (clinical benefit)

  All randomized patients with adequate baseline disease assessment with measurable disease, the disease under study and who start treatment on the assigned arm will be considered evaluable for clinical benefit (CB). The probability of CB on each randomized treatment arm will be estimated by dividing the number of patients with CB by the number of evaluable patients randomized to the treatment arm.

  Baseline up to 3 years

Secondary Outcomes (5)

• Progression free survival (PFS)

  Baseline up to 3 years

• Objective Response (OR)

  Baseline up to 3 years

• Overall Survival (OS)

  Baseline up to 6 years

• Time to Progression (TTP)

  Baseline up to 3 years

• Duration of Response (DR)

  Baseline up to 3 years

Other Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Baseline up to 3 years

Study Arms (2)

Arm A

EXPERIMENTAL

Palbociclib monoterapy

Drug: Palbociclib

Arm B

EXPERIMENTAL

Palbociclib + HT (Anastrozole, Letrozole, Exemestane, Fulvestrant)

Drug: Palbociclib; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Fulvestrant

Interventions

Palbociclib DRUG

Palbociclib 125 mg/day orally in an ongoing 3:1 schedule (3 weeks on/1 week off)

Also known as: PD0332991

Arm A; Arm B

Anastrozole DRUG

Continuation of prior anastrozole 1mg/day orally in a continuous regimen

Arm B

Letrozole DRUG

Continuation of prior letrozole 2.5mg/day orally in a continuous regimen

Arm B

Exemestane DRUG

Continuation of prior exemestane 25mg/day orally in a continuous regimen

Arm B

Fulvestrant DRUG

Continuation of prior fulvestrant 500mg intramuscular injection every 4 weeks in a continuous regimen

Arm B

Eligibility Criteria

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

You may qualify if:

• Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease
• ER positive tumor ≥ 10%
• HER2 negative breast cancer by FISH or IHC
• Progression of advanced breast cancer on first or second line endocrine therapy for advanced breast cancer
• Paraffin-embedded tumor available for centralized assessment of biomarkers
• Measurable disease according to RECIST 1.1 (bone only disease is allowed only if measurable).
• Postmenopausal status
• Eastern Cooperative Oncology Group (ECOG) Performance status 0 -2
• Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade \>1
• Adequate organ function

You may not qualify if:

• Unstable brain metastases
• Prior treatment with more than one line of CT or more than two lines of HT advanced breast cancer or any CDK inhibitor
• Current treatment with therapeutic doses of anticoagulant
• Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors / inducers, drugs that are predominantly metabolized by CYP3A with narrow therapeutic indices, drugs with the potential of prolonging QT interval
• Diagnosis of any secondary malignancy within the last 3 years
• Active inflammatory bowel disease or chronic diarrhea
• Known human immunodeficiency virus infection; active hepatitis C, active hepatitis B

Sponsors & Collaborators

• Fondazione Sandro Pitigliani: lead

Study Sites (6)

Azienda Ospedaliera Papa Giovanni Xxiii

Bergamo, 24127, Italy

Location

Ospedale Antonio Perrino

Brindisi, 72100, Italy

Location

Istituto Europeo Oncologia

Milan, 20141, Italy

Location

A.O.U. Federico Ii Di Napoli

Napoli, 80131, Italy

Location

Fondazione Maugeri

Pavia, 27100, Italy

Location

A.O.U. S. Maria Della Misericordia Di Udine

Udine, 33100, Italy

Location

Related Publications (2)

• Galardi F, De Luca F, Biagioni C, Migliaccio I, Curigliano G, Minisini AM, Bonechi M, Moretti E, Risi E, McCartney A, Benelli M, Romagnoli D, Cappadona S, Gabellini S, Guarducci C, Conti V, Biganzoli L, Di Leo A, Malorni L. Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial. Breast Cancer Res. 2021 Mar 24;23(1):38. doi: 10.1186/s13058-021-01415-w.

  PMID: 33761970 DERIVED

• Malorni L, Curigliano G, Minisini AM, Cinieri S, Tondini CA, D'Hollander K, Arpino G, Bernardo A, Martignetti A, Criscitiello C, Puglisi F, Pestrin M, Sanna G, Moretti E, Risi E, Biagioni C, McCartney A, Boni L, Buyse M, Migliaccio I, Biganzoli L, Di Leo A. Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial. Ann Oncol. 2018 Aug 1;29(8):1748-1754. doi: 10.1093/annonc/mdy214.

  PMID: 29893790 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Anastrozole; Letrozole; exemestane; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• LUCA MALORNI, MD

  Azienda USL 4 Prato

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: September 15, 2015
• Study Start: October 1, 2012
• Primary Completion: February 9, 2017
• Study Completion: February 9, 2017
• Last Updated: August 1, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)