Clinical trial NCT02549430: To Reverse ENDocrine Resistance Trial - PD 0332991 Monotherapy vs PD 0332991 in Combination With the Endocrine Therapy
Official title: Phase 2,Open-label,Multicenter,Randomized Study of PD0332991 (Oral CDK4/6 Inhibitor) Monotherapy and in Combination With the HT to Which the pt Has Progressed in the Previous Line for ER+,Her2- Post-menopausal Advanced Breast Cancer Pts
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Advanced breast cancer
Postmenopausal
ER positive
Her2 negative
Lead sponsor: Fondazione Sandro Pitigliani
Sponsor class: OTHER
First posted: 2015-09-15
Enrollment: 115
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: In a clinical context, there is a lack of molecular compounds with demonstrated clinical activity in delaying/reversing resistance to endocrine agents. CDK 4/6 inhibitors may represent a biologically-driven option in this context.

With the present study investigators aim to complement the ongoing trial on PD0332991 by acquiring information on its clinical activity in post-menopausal patients with ER positive, Her2 negative advanced breast cancer patients already pretreated with a first-line or second line endocrine therapy.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Incidence of complete response (CR), partial response (PR) or stable disease (SD) ≥24 weeks (clinical benefit)
timeFrame: Baseline up to 3 years
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: Baseline up to 3 years
measure: Objective Response (OR)
timeFrame: Baseline up to 3 years
measure: Overall Survival (OS)
timeFrame: Baseline up to 6 years
measure: Time to Progression (TTP)
timeFrame: Baseline up to 3 years
measure: Duration of Response (DR)
timeFrame: Baseline up to 3 years
Other outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Baseline up to 3 years
Locations:
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni Xxiii
city: Brindisi
country: Italy
facility: Ospedale Antonio Perrino
city: Milano
country: Italy
facility: Istituto Europeo Oncologia
city: Napoli
country: Italy
facility: A.O.U. Federico Ii Di Napoli
city: Pavia
country: Italy
facility: Fondazione Maugeri
city: Udine
country: Italy
facility: A.O.U. S. Maria Della Misericordia Di Udine
Study officials:
affiliation: Azienda USL 4 Prato
name: LUCA MALORNI, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.