Clinical Trials /

Study in Women With Advanced Breast Cancer Receiving Palbociclib With AI or Fulvestrant

NCT02894398

Description:

The purpose of this study is to evaluate the efficacy and quality of life in women with advanced breast cancer (locally advance inoperable or metastatic adenocarcinoma of the breast), HR+ / HER2-, who are treated with an aromatase inhibitor or fulvestrant as baseline therapy in combination with palbociclib (Ibrance)

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study in Women With Advanced Breast Cancer Receiving Palbociclib With AI or Fulvestrant
  • Official Title: Open-label, Multi-center, sINGlE Arm Clinical Study to Evaluate Efficacy/QoL in Women With HR+, HER2-, Regionally Recurrent or Metastatic Breast Cancer Receiving Palbociclib With an AI or Fulvestrant After Prior Endocrine Therapy

Clinical Trial IDs

  • ORG STUDY ID: iOM-04318
  • NCT ID: NCT02894398

Conditions

  • Breast Cancer
  • Hormone Receptor Positive Tumor
  • Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Interventions

DrugSynonymsArms
PalbociclibIbrancePalbociclib+AI or Fulvestrant
LetrozolePalbociclib+AI or Fulvestrant
AnastrozolePalbociclib+AI or Fulvestrant
ExemestanePalbociclib+AI or Fulvestrant
FulvestrantPalbociclib+AI or Fulvestrant

Purpose

The purpose of this study is to evaluate the efficacy and quality of life in women with advanced breast cancer (locally advance inoperable or metastatic adenocarcinoma of the breast), HR+ / HER2-, who are treated with an aromatase inhibitor or fulvestrant as baseline therapy in combination with palbociclib (Ibrance)

Detailed Description

      This is a prospective, open-label, multi-center, single arm, non-comparative phase II study
      in women with HR+/HER2- advanced breast cancer receiving palbociclib in addition to an
      aromatase inhibitor or fulvestrant. The study will take place in Germany (85 study centers).

      In total, 360 patients will be enrolled in this study. 6 treatment groups are planned. The
      study seeks to recruit 60 (58-62) patients per recruitment group. For first-line treatment
      with palbociclib - and letrozole (Enrollment Group 1), anastrozole (Enrollment Group 2),
      exemestane (Enrollment Group 3) or fulvestrant (Enrollment Group 4) and 60 (58-62) patients
      for second- or later-line treatment with palbociclib -and letrozole (Enrollment Group 5) or
      fulvestrant (Enrollment Group 6). Recruitment will be centrally monitored to allow closure of
      a respective group as soon as 60 (58-62) patients have been enrolled.

      Treatment will be continued until disease progression, intolerable toxicity, death or any
      other reason. In case a combination partner is discontinued, palbociclib has to be
      discontinued. In case treatment with palbociclib is stopped, combination partner can be
      continued according to investigator's discretion. Irrespectively of the combination partner,
      the discontinuation of palbociclib is defined as end of treatment (EOT) in this study. After
      EOT the patient enters the follow-up period.

      Primary end point is clinical benefit rate 24 weeks after the first study treatment of the
      patient.

      A study independent, decentral, "virtual" biobank will be established. All patients will be
      asked to give consent for their tumor samples to be used for future investigational research.
      Study sites will inform the local pathologists about the patient's consent and ask for the
      tissue sample to be reserved for future analyses. The site is requested to collect contact
      details of the pathologist storing the tumor sample, the sample's identification number(s),
      and to document these in the eCRF.

      The decision to perform subsequent investigational research studies on collected samples will
      be based on outcome data from this study or from new scientific findings related to the drug
      class or disease, as well as reagent and assay availability.
    

Trial Arms

NameTypeDescriptionInterventions
Palbociclib+AI or FulvestrantExperimentalLetrozole as first-line or later line, Anastrozole as first-line, Exemestane as first-line, Fulvestrant as first-line or later line after prior endocrine therapy.
  • Palbociclib
  • Letrozole
  • Anastrozole
  • Exemestane
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          1. Personally signed written informed consent prior to beginning protocol specific
             procedures, including expected cooperation of the patient for the treatment and
             follow-up, must be obtained and documented according to the local regulatory
             requirements

          2. Women with proven diagnosis of advanced, defined as locally advanced inoperable or
             metastatic, adenocarcinoma of the breast

          3. Hormone-receptor-positive (HR+) disease, defined as estrogen-receptor-positive (ER+)
             and/or progesterone-receptor-positive (PgR+)

          4. Human epidermal growth factor receptor 2-negative (HER2-) disease (HER2 neg/+ or
             HER2++ with CISH/FISH neg.)

          5. Pre-/perimenopausal women receiving concomitant therapy with an luteinizing
             hormone-releasing hormone (LHRH) agonist / ovarian ablation or postmenopausal status

          6. Age ≥18 years

          7. Measurable disease as per Response Evaluation Criteria in Solid Tumors [RECIST] or
             bone-only disease

          8. Patients scheduled for palliative treatment with an combination partner for first- or
             later-line

          9. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

         10. Adequate organ and marrow function

         11. Resolution of all acute toxic effects of prior therapy, including radiotherapy Grade
             <1 (except toxicities not considered a safety risk for the patient) and recovery from
             surgical procedures

         12. Fluent in spoken and written German

        Exclusion Criteria:

          1. Prior treatment with any CDK4/6 inhibitor

          2. Prior adjuvant therapy with the respective endocrine combination partner if last
             intake <12 months prior to entering the study

          3. Prior palliative therapy with the respective endocrine combination partner

          4. More than one prior palliative chemotherapy

          5. 5. Known hypersensitivity to letrozole, anastrozole, exemestane, fulvestrant or any of
             their excipients

          6. Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4
             (refer to Appendix 15.4)

          7. Current use of preparations containing St. John's Wort

          8. Participation in other studies involving investigational drug(s) (Phases I-IV) within
             2 weeks before the current study treatment begins

          9. QTc > 480 msec on the screening ECG (using the QTcF formula and/or the QTcB (Bazett)
             formula); history of QT syndrome, Brugada syndrome or known history of QTc
             prolongation, or Torsade de Pointes

         10. High cardiovascular risk, including, but not limited to recent myocardial infarction,
             severe/unstable angina and severe cardiac dysrhythmias in the past 6 months prior to
             enrollment

         11. Patients with advanced symptomatic, visceral spread, that were at risk of
             life-threatening complications in the short term (including patients with massive
             uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and
             over 50% liver involvement)

         12. Diagnosis of any second malignancy within the last 3 years prior to enrollment, except
             for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
             of the cervix

         13. Known, not-irradiated CNS metastases
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Benefit Rate (CBR)
Time Frame:24 weeks after first administration of Palbociclib in combination with AI / fulvestrant
Safety Issue:
Description:CBR is defined as complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.

Secondary Outcome Measures

Measure:Number of participants with Adverse Events as assessed by CTCAE V4.0
Time Frame:From Date of Signed informed consent until PD, assessed up to 60 months.
Safety Issue:
Description:Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v.4.03), and seriousness
Measure:Clinical Benefit Rate (CBR)
Time Frame:48 weeks after first administration of Palbociclib in combination with AI / fulvestrant
Safety Issue:
Description:CBR is defined as complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.
Measure:Progression-free Survival rate
Time Frame:At 48 weeks (all patients) and 2 years (first-line patients only) after first administration of Palbociclib in combination with AI / fulvestrant
Safety Issue:
Description:
Measure:Overall Survival rate
Time Frame:At 48 weeks after first administration of Palbociclib in combination with AI / fulvestrant and yearly until EOS, assessed up to 60 months.
Safety Issue:
Description:
Measure:Time on treatment
Time Frame:From day of first treatment until permanent discontinuation (EOT), assessed up to 60 months.
Safety Issue:
Description:
Measure:Dosage
Time Frame:From day of first treatment until EOT, assessed up to 60 months.
Safety Issue:
Description:starting dose (mg) adjusted doses (mg)
Measure:Adminstration schedule
Time Frame:From day of first treatment until EOT, assessed up to 60 months.
Safety Issue:
Description:- dates of administration
Measure:Health-related quality of life (QoL)
Time Frame:From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.
Safety Issue:
Description:Health-related QoL will be assessed with the FACT-B (Functional Assessment of Cancer Therapy-Breast) questionnaire
Measure:Health-related fatigue
Time Frame:From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.
Safety Issue:
Description:Fatigue will be assessed with the BFI (Brief Fatigue Inventory) questionnaire
Measure:Health-related anxiety and depression
Time Frame:From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.
Safety Issue:
Description:Depression and anxiety will be assessed with the HADS-D (Hospital Anxiety and Depression Scale) questionnaire
Measure:Physician's assessment of patient's overall health status and change in health status compared to previous visit
Time Frame:From Screening until disease progression or start of next anti-cancer therapy, assessed up to 60 months.
Safety Issue:
Description:Assessed by 2 items at each cycle/at scheduled patient visit

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:iOMEDICO AG

Trial Keywords

  • HR+
  • HER2-
  • Locally advanced (inoperable or metastatic) Breast Cancer
  • Palbociclib
  • Aromatase inhibitor or fulvestrant
  • Pre-/perimenopausal receiving LHRH agonist / ovarian ablation
  • Postmenopausal

Last Updated

October 17, 2017