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

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ClinicalTrials.gov Identifier: NCT02549430
Recruitment Status : Completed
First Posted : September 15, 2015
Last Update Posted : August 1, 2017
Sponsor:
Information provided by (Responsible Party):
Fondazione Sandro Pitigliani

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Palbociclib Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: Fulvestrant Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 115 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2012
Actual Primary Completion Date : February 9, 2017
Actual Study Completion Date : February 9, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Palbociclib

Arm Intervention/treatment
Experimental: Arm A
Palbociclib monoterapy
Drug: Palbociclib
Palbociclib 125 mg/day orally in an ongoing 3:1 schedule (3 weeks on/1 week off)
Other Name: PD0332991

Experimental: Arm B
Palbociclib + HT (Anastrozole, Letrozole, Exemestane, Fulvestrant)
Drug: Palbociclib
Palbociclib 125 mg/day orally in an ongoing 3:1 schedule (3 weeks on/1 week off)
Other Name: PD0332991

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

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

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

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




Primary Outcome Measures :
  1. Incidence of complete response (CR), partial response (PR) or stable disease (SD) ≥24 weeks (clinical benefit) [ Time Frame: Baseline up to 3 years ]
    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.


Secondary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Baseline up to 3 years ]
    PFS is the time from randomization date to date of first documentation of progression or death due to any cause, whichever occurs first. Documentation of progression must be by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. All patients randomized will be considered evaluable for PFS.

  2. Objective Response (OR) [ Time Frame: Baseline up to 3 years ]
    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 objective response (CR or PR). The probability of OR on each randomized treatment arm will be estimated by dividing the number of patients with OR by the number of evaluable patients randomized to the respective treatment arm ("response rate").

  3. Overall Survival (OS) [ Time Frame: Baseline up to 6 years ]
    OS is the time from randomization date to date of death due to any cause. All patients randomized will be considered evaluable for OS.

  4. Time to Progression (TTP) [ Time Frame: Baseline up to 3 years ]
    TTP is the time from randomization date to date of first documentation of objective progression. All patients randomized will be considered evaluable for TTP.

  5. Duration of Response (DR) [ Time Frame: Baseline up to 3 years ]
    For patients with an objective response (CR or PR), duration of response is the time from first documentation of CR or PR to date of first documentation of objective progression or death. Date of first documentation of progression and date of first documentation of CR or PR will be based on investigator assessment of response.


Other Outcome Measures:
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Baseline up to 3 years ]
    All patients treated with at least one dose of trial treatment will be included in safety analyses. Adverse events will be summarized by treatment and by the frequency of patients experiencing treatment emergent adverse events corresponding to body systems and MedDRA preferred term. Adverse events will be graded by worst NCI CTCAE v4.0 grade.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02549430


Locations
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Italy
Azienda Ospedaliera Papa Giovanni Xxiii
Bergamo, Italy, 24127
Ospedale Antonio Perrino
Brindisi, Italy, 72100
Istituto Europeo Oncologia
Milano, Italy, 20141
A.O.U. Federico Ii Di Napoli
Napoli, Italy, 80131
Fondazione Maugeri
Pavia, Italy, 27100
A.O.U. S. Maria Della Misericordia Di Udine
Udine, Italy, 33100
Sponsors and Collaborators
Fondazione Sandro Pitigliani
Investigators
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Principal Investigator: LUCA MALORNI, MD Azienda USL 4 Prato
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Fondazione Sandro Pitigliani
ClinicalTrials.gov Identifier: NCT02549430    
Other Study ID Numbers: TREnd
2011-005637-38 ( EudraCT Number )
First Posted: September 15, 2015    Key Record Dates
Last Update Posted: August 1, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Fondazione Sandro Pitigliani:
Advanced breast cancer
Postmenopausal
ER positive
Her2 negative
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Fulvestrant
Palbociclib
Anastrozole
Exemestane
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Protein Kinase Inhibitors