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Completed

NCT Number: NCT02549430

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Azienda Ospedaliera Papa Giovanni Xxiii, Bergamo, Italy

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Palbociclib

Drug

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

Other names: PD0332991

Anastrozole

Drug

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

letrozole

Drug

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

Exemestane

Drug

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

Fulvestrant

Drug

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

Primary outcomes

  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 outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Fondazione Sandro Pitigliani

Other

Registry information

Official study 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

Acronym: TREnd

Important dates

Study start
2012
Primary completion
2017
Study completion
2017
First posted
Sep 15, 2015
Registry last updated
Aug 1, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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