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

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ClinicalTrials.gov Identifier: NCT03870919
Recruitment Status : Recruiting
First Posted : March 12, 2019
Last Update Posted : September 16, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
UNICANCER

Study Description
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Brief Summary:

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 months 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.


Condition or disease Intervention/treatment Phase
Breast Cancer Stage IV Radiotherapy Surgery Drug: Palbociclib Other: locoregional treatment Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 23, 2019
Estimated Primary Completion Date : October 23, 2023
Estimated Study Completion Date : October 23, 2026

Resource links provided by the National Library of Medicine

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

Arms and Interventions
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Arm Intervention/treatment
Palbociclib + locoregional treatment
All 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
 Drug: Palbociclib

The included patients will first receive the following systemic treatment according standard of care:

  • Non-steroidal aromatase inhibitor (letrozole)
  • Palbociclib
  • Monthly Luteinizing hormone-releasing hormone (LHRH) analogue for non-menopausal patients only. Surgical bilateral oophorectomy is an acceptable option.

Other: locoregional treatment
After 6 courses of systemic treatment initiation, the loco-regional treatment of the primary tumour will be performed: surgery (conservative or mastectomy) with or without radiotherapy, or radiotherapy


Outcome Measures
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Primary Outcome Measures :
  1. Overall survival rate in patients receiving the letrozole plus palbociclib combination plus locoregional treatment [ Time Frame: 24 months ]
    Overall survival


Secondary Outcome Measures :
  1. Clinical response rate on both primary tumour and metastasis disease [ Time Frame: 24 months ]
    Follow-up of the disease status by imaging exams until surgery

  2. Pathological response rate in primary tumour [ Time Frame: 26 weeks ]
    Pathological response (tumour size, cellularity... ) evaluated at the surgery or at the biopsy

  3. Conversion rate of breast surgery (conservative-radical) [ Time Frame: 26 weeks ]
    Rate of modification of indication of mastectomy

  4. Locoregional control rate [ Time Frame: 60 months ]
    Rate of locoregional recurrence after surgery and/or radiotherapy

  5. Progression-free survival (PFS) [ Time Frame: 60 months ]
    Follow-up of the disease status by imaging exams

  6. Overall survival [ Time Frame: 60 months ]
  7. Incidence of combined therapies in terms of adverse events [ Time Frame: 60 months ]
    Will be evaluated using the National Cancer Institute - common terminology criteria for adverse events (NCI-CTCAE) v5.0

  8. Registration of post letrozole-CDKi therapies [ Time Frame: 60 months ]
    Records of cancer treatments prescribed to patients after disease progression

  9. Evolution of quality of life during treatment [ Time Frame: 60 months ]
    self-administered questionnaire of quality of life EORTC QLQ-C30 taking into account the patient's activity and his/her physical and psychological state

  10. Evolution of quality of life during treatment [ Time Frame: 60 months ]
    self-administered questionnaire of quality of life EORTC QLQ-BR23, complementary module to QLQ C30 questionnaire, is more specifically interested in patients with se cancer and the impact of treatment on their lives

  11. Evolution of quality of life during treatment [ Time Frame: 60 months ]
    self-administered questionnaire of quality of life Euroquol EQ-5D-5L consists of a descriptive system and a visual scale


Eligibility Criteria
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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:

  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 Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 and/or PET Response Criteria in Solid Tumours (PERCIST) 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
Contacts and Locations
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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): NCT03870919


Contacts
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Contact: Helene MANDUZIO, PhD +33 (0)1 71 93 63 63 palatine@unicancer.fr

Locations
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Sponsors and Collaborators
UNICANCER
Pfizer
Investigators
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Principal Investigator: Delphine Hequet, MD Institut Curie
More Information
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Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT03870919    
Other Study ID Numbers: UC-0140/1814
2019-A00570-57 ( Registry Identifier: ANSM )
First Posted: March 12, 2019    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNICANCER:
therapies combination
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
 Palbociclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action