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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03809988
Recruitment Status : Not yet recruiting
First Posted : January 18, 2019
Last Update Posted : January 21, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
MedSIR

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

Condition or disease Intervention/treatment Phase
Breast Cancer Advanced Breast Cancer Hormone Receptor Positive Tumor Human Epidermal Growth Factor 2 Negative Carcinoma of Breast Drug: Palbociclib Drug: Endocrine therapy Phase 2

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 biopsiable 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 198 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: International,Multicenter,Randomized,Open-label, Phase II to Evaluate the Efficacy and Safety of Continuation of Palbociclib+2nd Line Endocrine Therapy in HR+/HER2- ABC Patients Who Had Clinical Benefit During 1st Line Palbociclib.
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Arm Intervention/treatment
Experimental: Interventional Arm (Arm A)
Patients 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).
Drug: Palbociclib
Palbociclib capsules orally once daily (QD) (at 100mg or 125mg depending on previous treatment dose) for 21 days every four weeks
Other Name: IBRANCE

Drug: Endocrine therapy
Endocrine therapy alone (letrozole or fulvestrant)
Other Names:
  • letrozole
  • fulvestrant

Active Comparator: Control Arm (Arm B)
Patients will receive endocrine therapy alone (letrozole or fulvestrant).
Drug: Endocrine therapy
Endocrine therapy alone (letrozole or fulvestrant)
Other Names:
  • letrozole
  • fulvestrant




Primary Outcome Measures :
  1. PFS (Progression-free survival) [ Time Frame: Baseline up to 29 months ]
    From a clinical point of view, the primary endpoint for this study is the PFS (progression-free survival) - 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 :
  1. Safety AEs [ Time Frame: Baseline up to 29 months ]
    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.

  2. Efficacy (ORR) [ Time Frame: Baseline up to 29 months ]
    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

  3. Efficacy (Quality of Life) [ Time Frame: Baseline up to 42 months ]
    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.

  4. Efficacy of subgroup analysis [ Time Frame: Baseline up to 42 months ]
    To perform subgroup analysis for primary and secondary endpoints in stratified groups of patients.

  5. Compare efficacy [ Time Frame: Baseline up to 42 months ]
    To compare the time to first chemotherapy of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone.

  6. Exploratory objectives (molecular markers) [ Time Frame: Baseline up to 42 months ]
    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).

  7. Exploratory objectives (intrinsic molecular subtypes) [ Time Frame: Baseline up to 42 months ]
    To explore correlations between the intrinsic molecular subtypes and efficacy/safety findings in patients with HR-positive/HER2- negative ABC.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. 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 National Comprehensive Cancer Network and ASCO American Society of Clinical Oncology 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.

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): NCT03809988


Contacts
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Contact: Pilar Bescós +34 635 064 603 pilar.bescos@medsir.org
Contact: Alicia García +34 611 261 467 alicia.garcia@medsir.org

Locations
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Spain
ICO Badalona
Badalona, Barcelona, Spain
Hospital Provincial de Castellón
Castello, Castelló, Spain
Consorci Sanitari de Terrassa Not yet recruiting
Terrassa, Terrasa, Spain, 08191
Contact: Angels Arcusa Lanza         
Principal Investigator: Angels Arcusa Lanza         
Centro Oncológico de Galicia Not yet recruiting
A Coruña, Spain, 15009
Contact: Manuel Ramos Vázquez         
Principal Investigator: Manuel Ramos Vázquez         
Institut Català d'Oncologia Bellvitge Not yet recruiting
Barcelona, Spain, 08908
Contact: Adela Fernández         
Principal Investigator: Adela Fernández         
H. Vall Hebrón
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital de Basurto Not yet recruiting
Bilbao, Spain, 48013
Contact: Purificación Martínez         
Principal Investigator: Purificación Martínez         
Hospital San Pedro de Alcantara Not yet recruiting
Cáceres, Spain, 10003
Contact: Santiago González         
Principal Investigator: Santiago González         
Institut Català d'Oncologia
Girona, Spain
Hospital Arnau de Vilanova
Lleida, Spain
Hospital Universitario Sanchinarro Not yet recruiting
Madrid, Spain, 28050
Contact: Estela Vega         
Principal Investigator: Estela Vega         
Hospital Clinico San Carlos
Madrid, Spain
Hospital La Paz
Madrid, Spain
Hospital Regional Universitario de Malaga Not yet recruiting
Málaga, Spain, 29010
Contact: Tamara Diaz Redondo         
Principal Investigator: Tamara Diaz Redondo         
Hospital Universitari Son Espases Not yet recruiting
Palma De Mallorca, Spain, 07120
Contact: Antonia Perello Martorell         
Principal Investigator: Antonia Perello Martorell         
Hospital Sant Joan
Reus, Spain
Hospital Universitario Virgen de la Macarena Not yet recruiting
Sevilla, Spain, 41009
Contact: Luis de la Cruz Merino         
Principal Investigator: Luis de la Cruz Merino         
Hospital Universitario Virgen del Rocío
Sevilla, Spain
Instituto Valenciano de Oncología IVO Not yet recruiting
Valencia, Spain, 46009
Contact: Kino Gávila         
Principal Investigator: Kino Gávila         
Hospital Arnau de Vilanova de Valencia
Valencia, Spain
Hospital General Universitari de Valencia
Valencia, Spain
Hospital Universitari i Politecnic La Fe
Valencia, Spain
Hospital Álvaro Cunqueiro Not yet recruiting
Vigo, Spain, 36312
Contact: Isaura Fernandez Perez         
Principal Investigator: Isaura Fernandez Perez         
Hospital Lozano Blesa
Zaragoza, Spain, 50009
Hospital Miguel Servet
Zaragoza, Spain
Sponsors and Collaborators
MedSIR
Pfizer
Investigators
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Principal Investigator: José Perez MedSIR

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Responsible Party: MedSIR
ClinicalTrials.gov Identifier: NCT03809988     History of Changes
Other Study ID Numbers: MedOPP068
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: January 21, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by MedSIR:
HR
breast cancer
ABC
progesterone receptor
HER2
advanced
estrogen receptor

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Fulvestrant
Palbociclib
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Protein Kinase Inhibitors