Clinical Trials /

Locoregional Treatment and Palbociclib in de Novo, Treatment Naive, Stage IV ER+, HER2- Breast Cancer Patients

NCT03870919

Description:

Approximately 3.5% to 6% of newly diagnosed breast cancer patients are stage IV metastatic. De novo metastatic breast cancer accounts for 20% to 25% of these cases. Despite a decrease in mortality in Europe and North America due to early detection and access to treatment, breast cancer remains the 2nd leading cause of cancer deaths in developed countries after lung cancer and the world's leading cause. In the ESME French national retrospective cohort (NCT03275311), the newly diagnosed estrogen receptor (ER)-positive and HER2-negative (luminal) metastatic patients had a 59.1 month overall survival (OS) for pre-menopausal women and 44.7 months for postmenopausal women. In the same cohort, the median OS was 47.4 months for de novo metastatic patients with hormone receptor (HR)-positive / HER2-negative breast cancer. The most important current treatment for metastatic breast cancer remains systemic therapy. Surgery and radiation are mainly used to treat symptoms. However, more than 15 retrospective studies have assessed the impact of locoregional treatment on relapse and OS. These studies suggested an improvement of the OS in patients with de novo metastatic breast cancer thanks to the addition of locoregional treatment to systemic therapy. Recent data from the ESME cohort suggest that patients with de novo luminal or HER2-positive metastatic breast cancer may benefit from local treatment of the primary tumor. Several prospective trials have attempted to demonstrate the benefit of locoregional treatment with mixed results. This can be explained by a limited power of statistical analysis, on the recruitment of patients with breast cancer of all types, and on a limited access to effective systemic therapies in some cases and all before the area of anti CD4/6 which is the current standard treatment in patients with HR-positive / HER2-negative luminal metastatic disease. However, guidelines indicate that a "multimodal approach, including curative locoregional treatments, should be considered". As a result, many clinicians offer locoregional treatment of the primary tumor, especially if there is a good response to the first line of systematic treatment. Taken together, these data underscore the need for an evaluation of the value of combined therapy - endocrine therapy - CDK4/6 inhibitor and locoregional treatment - in this population of patients with newly diagnosed HR-positive / HER2-negative breast cancer.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Locoregional Treatment and Palbociclib in de Novo, Treatment Naive, Stage IV ER+, HER2- Breast Cancer Patients
  • Official Title: PALbociclib in Advanced Breast Cancer: Therapy INtegrating locorEgional Treatment and Palbociclib in de Novo, Treatment Naive, Stage IV ER+, HER2- Breast Cancer Patients

Clinical Trial IDs

  • ORG STUDY ID: UC 0140-1814
  • SECONDARY ID: 2019-A00570-57
  • NCT ID: NCT03870919

Conditions

  • Breast Cancer Stage IV
  • Radiotherapy
  • Surgery

Interventions

DrugSynonymsArms
PalbociclibPalbociclib + locoregional treatment

Purpose

Approximately 3.5% to 6% of newly diagnosed breast cancer patients are stage IV metastatic. De novo metastatic breast cancer accounts for 20% to 25% of these cases. Despite a decrease in mortality in Europe and North America due to early detection and access to treatment, breast cancer remains the 2nd leading cause of cancer deaths in developed countries after lung cancer and the world's leading cause. In the ESME French national retrospective cohort (NCT03275311), the newly diagnosed estrogen receptor (ER)-positive and HER2-negative (luminal) metastatic patients had a 59.1 month overall survival (OS) for pre-menopausal women and 44.7 months for postmenopausal women. In the same cohort, the median OS was 47.4 months for de novo metastatic patients with hormone receptor (HR)-positive / HER2-negative breast cancer. The most important current treatment for metastatic breast cancer remains systemic therapy. Surgery and radiation are mainly used to treat symptoms. However, more than 15 retrospective studies have assessed the impact of locoregional treatment on relapse and OS. These studies suggested an improvement of the OS in patients with de novo metastatic breast cancer thanks to the addition of locoregional treatment to systemic therapy. Recent data from the ESME cohort suggest that patients with de novo luminal or HER2-positive metastatic breast cancer may benefit from local treatment of the primary tumor. Several prospective trials have attempted to demonstrate the benefit of locoregional treatment with mixed results. This can be explained by a limited power of statistical analysis, on the recruitment of patients with breast cancer of all types, and on a limited access to effective systemic therapies in some cases and all before the area of anti CD4/6 which is the current standard treatment in patients with HR-positive / HER2-negative luminal metastatic disease. However, guidelines indicate that a "multimodal approach, including curative locoregional treatments, should be considered". As a result, many clinicians offer locoregional treatment of the primary tumor, especially if there is a good response to the first line of systematic treatment. Taken together, these data underscore the need for an evaluation of the value of combined therapy - endocrine therapy - CDK4/6 inhibitor and locoregional treatment - in this population of patients with newly diagnosed HR-positive / HER2-negative breast cancer.

Trial Arms

NameTypeDescriptionInterventions
Palbociclib + locoregional treatmentOtherAll patients will receive the standard of care treatment ie Palbociclib + letrozole for 24-26 weeks. After this period, patient will have the most adapted locoregional treatment ie surgery (conservative or mastectomy) with or without radiotherapy, or radiotherapy. The palbociclib will be continued until progression
  • Palbociclib

Eligibility Criteria

        Inclusion Criteria:

          1. Women with newly diagnosed and histologically proven de novo adenocarcinoma of the
             breast, Any T, any N, with at least one metastatic site measurable and/or
             non-measurable according to RECIST (Response Evaluation Criteria In Solid Tumours)
             v1.1 and/or PERCIST (PET Response Criteria in Solid Tumours) v1.0. For patients with
             only bone metastases, at least one lytic and non-irradiated lesion must be present

          2. Estrogen Receptor (ER)-positive and HER2-negative breast cancer. To be considered as
             ER-positive, the biopsy of the primary tumour must display at least 10% of cancer
             cells with positive ER staining. HER2-positive is defined as IHC3+ or FISH/CISH
             amplified according to 2018 criteria

          3. Age ≥18 years

          4. Eastern Cooperative Oncology Group (ECOG) ≤2

          5. Indication for treatment with palbociclib and letrozole (with or without ovarian
             suppression)

          6. Frozen primary breast tumour sample available

          7. Women of childbearing potential must have a negative serum or urine pregnancy test
             done within 14 days before inclusion

          8. Patients must agree to use adequate contraception methods for the duration of the
             study and for within 21 days after completing treatment

          9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and any protocol-related procedures including absence of co-morbidities
             preventing surgery and or radiotherapy and any psychological, familial, sociological
             or geographical condition potentially hampering compliance with the study protocol and
             follow-up schedule. Those conditions should be discussed with the patient before
             registration in the trial

         10. Patient affiliated to a social security system

         11. Written informed consent obtained prior to performing any protocol-related procedures
             including screening evaluations

        Exclusion Criteria:

          1. Patients with advanced, symptomatic, visceral spread at a risk for short-term,
             life-threatening complications according to investigator judgement and at risk for
             visceral crisis as defined by ABC4

          2. Women with previously diagnosed and treated ipsilateral adenocarcinoma of the breast

          3. Women with previously treated or concomitant contralateral breast cancer except for
             Ductal carcinoma in situ (DCIS) treated with curative intent

          4. Patients with another concomitant cancer

          5. Concurrent enrolment in another clinical trial in which investigational therapies are
             administered or administration of an investigational drug within 30 days before
             inclusion

          6. Pregnant women or women who are breast-feeding

          7. Inability or willingness to swallow oral medication

          8. Known prior severe hypersensitivity to palbociclib or any component in its formulation
             including known severe hypersensitivity reactions to study drug (NCI-CTCAE v5.0 Grade
             ≥3)

          9. Patients using drugs that could have pharmacokinetics interaction with investigational
             drugs

         10. HIV, hepatitis (B and C)

         11. Active infection

         12. Prior therapy for metastatic breast cancer (systemic or local)

         13. Persons deprived of their freedom or under guardianship or incapable of giving consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival rate in patients receiving the letrozole plus palbociclib combination plus locoregional treatment
Time Frame:24 months
Safety Issue:
Description:Overall survival

Secondary Outcome Measures

Measure:Clinical response rate on both primary tumour and metastasis disease
Time Frame:24 months
Safety Issue:
Description:Follow-up of the disease status by imaging exams until surgery
Measure:Pathological response rate in primary tumour
Time Frame:26 weeks
Safety Issue:
Description:Pathological response (tumour size, cellularity... ) evaluated at the surgery or at the biopsy
Measure:Conversion rate of breast surgery (conservative-radical)
Time Frame:26 weeks
Safety Issue:
Description:Rate of modification of indication of mastectomy
Measure:Locoregional control rate
Time Frame:60 months
Safety Issue:
Description:Rate of locoregional recurrence after surgery and/or radiotherapy
Measure:Progression-free survival (PFS)
Time Frame:60 months
Safety Issue:
Description:Follow-up of the disease status by imaging exams
Measure:Overall survival
Time Frame:60 months
Safety Issue:
Description:
Measure:Incidence of combined therapies in terms of adverse events
Time Frame:60 months
Safety Issue:
Description:Will be evaluated using the National Cancer Institute - common terminology criteria for adverse events (NCI-CTCAE) v5.0
Measure:Registration of post letrozole-CDKi therapies
Time Frame:60 months
Safety Issue:
Description:Records of cancer treatments prescribed to patients after disease progression
Measure:Evolution of quality of life during treatment
Time Frame:60 months
Safety Issue:
Description:QLQ-C30
Measure:Evolution of quality of life during treatment
Time Frame:60 months
Safety Issue:
Description:QLQ-BR23
Measure:Evolution of quality of life during treatment
Time Frame:60 months
Safety Issue:
Description:EQ-5D-5L

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:UNICANCER

Trial Keywords

  • therapies combination

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