Clinical Trials /

PALbociclib Rechallenge in horMone Receptor-posItive/HER2- Negative Advanced Breast Cancer (PALMIRA)

NCT03809988

Description:

Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer (ABC)

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PALbociclib Rechallenge in horMone Receptor-posItive/HER2- Negative Advanced Breast Cancer (PALMIRA)
  • Official Title: International, Multicenter, Randomized, Open-label, Phase II to Evaluate the Efficacy and Safety of Continuation of Palbociclib+2L Endocrine Therapy in HR+/HER2- ABC Patients Who Have Achieved Clinical Benefit During 1L Palbociclib.

Clinical Trial IDs

  • ORG STUDY ID: MedOPP068
  • NCT ID: NCT03809988

Conditions

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

Interventions

DrugSynonymsArms
PalbociclibIBRANCEInterventional Arm (Arm A)
Endocrine therapyletrozol, fulvestrantInterventional Arm (Arm A)

Purpose

Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer (ABC)

Detailed Description

      Pre- and post-menopausal women age ≥ 18 years with HR-positive and HER2-negative with ABC
      that had previously received first-line endocrine therapy in combination with palbociclib and
      had achieved clinical benefit during palbociclib-based treatment. Patients relapsing on a
      palbociclib-based regimen in the adjuvant setting are also eligible. Patients are not
      eligible if they are candidates for a local treatment with a curative intention. Evidence of
      either measurable and biopsable metastatic disease (as for Response Evaluation Criteria In
      Solid Tumors (RECIST v.1.1)) or non-measurable disease with bone lesion is required.
      Pre-menopausal women must be under treatment with luteinizing hormone-releasing hormone
      (LHRH) analogues.
    

Trial Arms

NameTypeDescriptionInterventions
Interventional Arm (Arm A)ExperimentalPatients will receive palbociclib capsules orally once daily (QD) (at 100mg or 125mg depending on previous treatment dose) for 21 days every four weeks in combination with endocrine therapy (letrozole or fulvestrant).
  • Palbociclib
  • Endocrine therapy
Control Arm (Arm B)Active ComparatorPatients will receive endocrine therapy alone (letrozole or fulvestrant).
  • Endocrine therapy

Eligibility Criteria

        Inclusion Criteria:

          1. Female patients over 18 years of age.

          2. Pre-menopausal women provided they are being treated with a LHRH analogue for at least
             28 days (if shorter, post-menopausal levels of serum estradiol/Follicle-stimulating
             hormone (FSH) must be confirmed analytically) prior to study entry or post- menopausal
             women as defined by any of the following criteria:

               1. Age ≥60 years;

               2. Age <60 years and cessation of regular menses for at least 12 consecutive months
                  with no alternative pathological or physiological cause; and serum estradiol
                  and/or FSH level within the laboratory's reference range for postmenopausal
                  females;

               3. Documented bilateral oophorectomy.

          3. Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 1.

          4. Life expectancy greater or equal to 12 weeks.

          5. Histologically proven diagnosed of ABC not amenable to curative treatment.

          6. Documented recurrent ER-positive and/or progesterone receptor (PgR)-positive (with ≥1%
             positive stained cells (according to NCCN and ASCO guidelines) and HER2-negative (0-1+
             by immunohistochemistry (IHC) or 2+ and negative by in situ hybridization (ISH) test)
             breast cancer in the advanced setting.

          7. Radiological or clinical evidence of disease progression on first- line combination of
             palbociclib plus endocrine therapy (aromatase inhibitor (AI) or fulvestrant). Patients
             previously treated with the combination of palbociclib and tamoxifen will be excluded.

          8. Patients have achieved clinical benefit criteria to a first-line palbociclib-based
             endocrine regimen (defined as at least stable disease ≥ 24 weeks or partial or
             complete response confirmed or unconfirmed).

          9. Patients must have been treated with a stable minimum dose of 100 mg palbociclib
             during the last 2 cycles of the prior palbociclib-based regimen.

         10. Last dose of palbociclib administered not later than 8 weeks and not earlier than 7
             days from study entry, with the exception of patients relapsing on a palbociclib-based
             regimen in the adjuvant setting.

         11. Patients should not have been treated in the advanced setting with at least one of
             these endocrine therapy options: either fulvestrant or AI.

         12. Patients must have measurable disease or evaluable disease according to RECIST
             criteria v.1.1. Patients with only bone lesions are eligible.

         13. Willingness and ability to provide tumor biopsy (if feasible) both at the time of the
             inclusion and after disease progression in order to perform exploratory studies. If
             not feasible, patient eligibility should be evaluated by a Sponsor's qualified
             designee.

         14. Patients agree to collection of blood samples (liquid biopsy) at the time of
             inclusion, after 2 weeks of treatment, and upon progression or study termination.

         15. Adequate organ function: (Hematological, hepatic and renal)

         16. Patients who are willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

         17. Patients have been informed about the nature of study, and have agreed to participate
             in the study, and signed the informed consent form prior to participation in any
             study-related activities.

         18. Resolution of all acute toxic effects of prior anti-cancer therapy to grade 1

        Exclusion Criteria:

          1. HR or HER2 unknown disease.

          2. HER2-positive disease based on local laboratory results (performed by IHC / ISH test).

          3. Locally ABC candidate for curative treatment.

          4. Formal contraindication to endocrine therapy defined as visceral crisis and rapidly or
             symptomatic progressive visceral disease.

          5. Prior therapy with any other CDK4/6 inhibitor different from palbociclib.

          6. Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases,
             carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms,
             cerebral edema, and/or progressive growth. Patients with a history of CNS metastases
             or cord compression are eligible if they have been definitively treated and are
             clinically stable off anticonvulsants and steroids for at least 4 weeks before
             randomization.

          7. Patients are currently receiving food or drugs known to be strong inducers or
             inhibitors of CYP3A4.

          8. Current or prior malignancy which could affect compliance with the protocol or
             interpretation of results. Patients with curatively- treated non-melanoma skin cancer,
             non-muscle-invasive bladder cancer, or carcinoma in situ, among others, are generally
             eligible.

          9. No other systemic therapy for metastatic disease including chemotherapy,
             immunotherapy, targeted therapy (small molecules/ monoclonal antibodies), or endocrine
             therapy excluding first-line palbociclib-based regimen.

         10. Major surgery (defined as requiring general anesthesia) or significant traumatic
             injury within 2 weeks of start of study drug, or patients who have not recovered from
             the side effects of any major surgery, or patients who may require major surgery
             during the study.

         11. Radiotherapy or limited-field palliative radiotherapy within 7 days prior to study
             enrolment, or patients who have not recovered from radiotherapy-related toxicities to
             baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously
             irradiated.

         12. Use of concurrent investigational agents or other concomitant anticancer therapies.

         13. Active bleeding diathesis, previous history of bleeding diathesis, or chronic
             anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon
             as it is used as prophylaxis intention).

         14. Serious concomitant systemic disorder (e.g., active infection including HIV, or
             cardiac disease) incompatible with the study (at the discretion of investigator).

         15. Unable to swallow capsules or tablets.

         16. History of malabsorption syndrome or other condition that would interfere with enteral
             absorption.

         17. Any of the following within 6 months of randomization:

             myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of
             NCI-CTCAE v.5.0 grade ≥2, coronary/peripheral artery bypass graft, symptomatic
             congestive heart failure, cerebrovascular accident including transient ischemic
             attack, or symptomatic pulmonary embolism.

         18. Uncontrolled electrolyte disorders of NCI-CTCAE v.5.0 grade ≥ 2.

         19. Known hypersensitivity to palbociclib or any of its excipients.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS
Time Frame:Baseline up to 29 months
Safety Issue:
Description:From a clinical point of view, the primary endpoint for this study is the PFS - defined as the period of time from randomization until objective tumor progression or death - assessed by RECIST criteria v.1.1, of continuation of palbociclib treatment combined with second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy in pre- and post- menopausal women with HR-positive/HER2-negative ABC.

Secondary Outcome Measures

Measure:Safety AEs
Time Frame:Baseline up to 29 months
Safety Issue:
Description:Patient safety and adverse events (AEs) will be evaluated using the NCI-CTCAE v.5.0. Grade 3 and 4 AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the different treatment arms.
Measure:Efficacy (ORR)
Time Frame:Baseline up to 29 months
Safety Issue:
Description:To compare the objective response rate (ORR), the duration of response (DoR), the time to response (TTR), the clinical benefit rate (CBR), the time to progression (TTP), and the overall survival (OS) of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone
Measure:Efficacy (Quality of Life)
Time Frame:Baseline up to 42 months
Safety Issue:
Description:To compare the patient reported global Quality of Life (QOL), functioning and symptoms of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone.
Measure:Efficacy of subgroup analysis
Time Frame:Baseline up to 42 months
Safety Issue:
Description:To perform subgroup analysis for primary and secondary endpoints in stratified groups of patients.
Measure:Compare efficacy
Time Frame:Baseline up to 42 months
Safety Issue:
Description:To compare the time to first chemotherapy of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone.
Measure:Exploratory objectives (molecular markers)
Time Frame:Baseline up to 42 months
Safety Issue:
Description:To explore potential molecular markers of sensitivity and/or resistance for the combination and endocrine therapy alone, according to, but not limited to, the results obtained from the BioPER trial (NCT03184090).
Measure:Exploratory objectives (intrinsic molecular subtypes)
Time Frame:Baseline up to 42 months
Safety Issue:
Description:To explore correlations between the intrinsic molecular subtypes and efficacy/safety findings in patients with HR-positive/HER2- negative ABC.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:MedSIR

Trial Keywords

  • HR
  • breast cancer
  • ABC
  • PR
  • HER2
  • advanced

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