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Trial record 1 of 1 for:    DXCARTES
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Neoadjuvant Letrozole and Palbociclib in Patients With Stage II-IIIB Breast Cancer, HR+, HER2 - (DxCARTES)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03819010
Recruitment Status : Completed
First Posted : January 28, 2019
Last Update Posted : February 7, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
MedSIR

Brief Summary:
This is an international, multicenter, open-label, non-comparative, Simon´s two-stage design, phase II clinical trial.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Pre treatment Recurrence Score:18-25 Letrozole + Palbociclib Drug: Pre treatment Recurrence Score:26-100 Letrozole + Palbociclib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is an international, multicenter, open-label, non-comparative, Simon´s two-stage design, phase II clinical trial.
Masking: None (Open Label)
Masking Description: Two arms of patients (according to Recurrence Score results), but both arms will be treated with the same treatment
Primary Purpose: Treatment
Official Title: Neoadjuvant Letrozole + Palbociclib in Patients With II-IIIB BC,HR+, HER2-, Phenotype and Pretreatment Recurrence Score(RS):18-25 or 26-100 by Oncotype DX Breast RS Assay.Analysis of RS and Pathological Changes at Surgery
Actual Study Start Date : May 7, 2019
Actual Primary Completion Date : July 30, 2019
Actual Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: Pre treatment Recurrence Score:18-25 Letrozole + Palbociclib
Letrozole (2,5 mg/day during 28 days of each Cycle) + Palbociclib (125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer interventions: Letrozol (2,5 mg/day during 28 days of each Cycle)+ Palbociclib(125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer
Drug: Pre treatment Recurrence Score:18-25 Letrozole + Palbociclib
Letrozole(2,5 mg/day during 28 days of each Cycle) + Palbociclib(125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer for patients with pre-treatment recurrence Score of 18-25
Other Name: None othe intervention name

Active Comparator: Pre treatment Recurrence Score:26-100 Letrozole + Palbociclib
Letrozole (2,5 mg/day during 28 days of each Cycle) + Palbociclib (125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer interventions: Letrozol (2,5 mg/day during 28 days of each Cycle)+ Palbociclib(125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer
Drug: Pre treatment Recurrence Score:26-100 Letrozole + Palbociclib
Letrozole(2,5 mg/day during 28 days of each Cycle) + Palbociclib(125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer for patients with pre-treatment recurrence Score of 26-100
Other Name: None othe intervention name




Primary Outcome Measures :
  1. Difference on Recurrence Score between pre and post-treatment (molecular results) [ Time Frame: 6 months ]
    To explore after 6 months of treatment the ability of palbociclib in combination with letro-zole to induce global molecular changes measured by either the Oncotype DX Breast Recurrence Score® (the "Assay") test result at surgery (post-treatment Recurrence Score® (RS) result), or pathological Complete Response (pCR) in patients with aggres-sive luminal tumors (pre-treatment RS result 18-25 or 26-100, and Ki67>20).


Secondary Outcome Measures :
  1. Molecular changes [ Time Frame: 6 months ]
    Concordance rate among post-treatment RS result and residual cancer burden (RCB), Ki67, and preoperative endocrine prognostic index (PEPI) score

  2. Molecular induction [ Time Frame: 6 months of treatment ]
    To explore the ability of palbociclib in combination with letrozole to induce global mo-lecular reduction measured by either the post-treatment RS result, and/or Residual Cancer Burden (RCB), and/or Ki67 in patients with aggressive luminal tumors (pre-treatment RS result 18-25 or 26-100 and Ki67>20) after 6 months of treatment.

  3. Global molecular reduction [ Time Frame: 6 months of treatment ]
    To verify the ability of palbociclib in combination with letrozole to induce global mo-lecular changes (measured as either post-treatment RS≤25 or RCB score of 0-I) in >35% of patients in cohort B with pre-treatment RS 26-100;

  4. increase RS result [ Time Frame: 6 months of treatment ]
    To verify the ability of palbociclib in combination with letrozole to induce changes in RS result (measured as post-treatment RS 26-100) in <3% of patients in cohort A with pre-treatment RS 18-25;

  5. Evaluate the concordance rate between the RCB score (0- I vs. II-III) and the post-treatment RS result in both cohorts of patients after treatment with palbociclib in com-bination with letrozole; [ Time Frame: 6 months of treatment ]
    To evaluate the concordance rate between the RCB score (0- I vs. II-III) and the post-treatment RS result in both cohorts of patients after treatment with palbociclib in com-bination with letrozole;

  6. Evaluate the concordance rate between the pCR and the post-treatment RS re-sult in both cohorts of patients after treatment with palbociclib in combination with letro-zole; [ Time Frame: 6 month of treatment ]
    To evaluate the concordance rate between the pCR and the post-treatment RS re-sult in both cohorts of patients after treatment with palbociclib in combination with letro-zole;

  7. Changes in RS [ Time Frame: 6 month of treatment ]
    To determine the change in RS result as measured by median absolute value or median percentage after 6 months of treatment: from pre-treatment RS 18-25 to post-treatment RS 0-17 for patients in cohort A and from pre-treatment RS 26-100 to post-treatment RS≤25 for patients in cohort B.


Other Outcome Measures:
  1. overall repsonse [ Time Frame: 6 month of treatment ]
    To determine the Overall Response Rate (ORR) of patients treated with palbociclib in combination with letrozole.

  2. duration of response [ Time Frame: 6 month of treatment ]
    To evaluate the Duration of Response (DoR) of palbociclib in combination with letrozole.

  3. Time to response [ Time Frame: 6 month of treatment ]
    To evaluate the Time to Response (TTR) of palbociclib in combination with letrozole.

  4. Clinical benefit [ Time Frame: 6 month of treatment ]
    To assess the Clinical Benefit Rate (CBR) of palbociclib in combination with letrozole.

  5. Evaluate the Maximum Tumor Shrinkage of palbociclib in combination with letrozole [ Time Frame: 6 month of treatment ]
    To evaluate the Maximum Tumor Shrinkage of palbociclib in combination with letrozole

  6. Safety and tolerability of the combination Letrozole plus Palbociclib [ Time Frame: 6 month of treatment ]
    To assess the safety and tolerability of palbociclib in combination with letrozole. "Number of participants with treatment-related adverse events as assessed by CTCAE v4.0".



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
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Pre and post menopausal females
Accepts Healthy Volunteers:   No
Criteria

IInclusion criteria

Patients must meet ALL of the following inclusion criteria to be eligible for enrolment into the study:

  1. Female patients over 18 years of age.
  2. Patients have been informed about the nature of study, have agreed to participate in the study, and have signed the informed consent form prior to participation in any study-related activities.
  3. Premenopausal and postmenopausal women. Premenopausal women must be treated with LHRH analogue since patient pre- registration. Premenopausal or postmenopausal status should have been established before starting study treatment with letrozole plus palbociclib based on the following classification:

    1. Postmenopausal status is defined as either:

      • Prior bilateral oophorectomy; Or
      • Age>60 years; Or
      • Age<60 years and amenorrhoeic for 12 months in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression, and follicle-stimulating hormone (FSH) and estradiol in postmenopausal range.
    2. Premenopausal status is defined as all those women who do not meet any of above criteria.
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  5. Histologically confirmed infiltrating breast cancer.
  6. HR-positive (estrogen receptor [ER]-positive and/or progesterone receptor [PgR]-positive) EBCs (breast cancers that have at least 10% of cells staging positive for ER and/or PgR). ER and/or PgR status will be centrally confirmed by using immunohistochemistry (IHC) testing for an Allred score of 6-8 in at least one of them.
  7. Patients with HER2-negative breast cancer through in situ hybridization test (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], or silver enhanced in situ hybridization [SISH]) or negative immunohistochemical status of 0, 1+, or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required.
  8. Ki67 levels ≥ 20% confirmed by IHC testing in a central laboratory.
  9. Tumor size > 2,0 cm (T2-4 according to TNM staging system, but always > 2,0 cm) by mammogram, breast ultrasound, or breast magnetic resonance imaging (MRI).
  10. Patients must have a measurable disease by mammogram and/or breast ultrasound.
  11. Patients with two significant lesions (both larger than 1 cm and with more than 1 cm distance between them) will require tumor sample from both lesions and proper preoperative marking of both. To be registered, both lesions should fulfil inclusion criteria 5 and 6 and both tumor samples will be submitted. Patient with more than 2 significant lesions will not be eligible.
  12. Limited node involvement (N0-2, according to TNM staging system), assessed by ultrasound. Sentinel lymph node biopsy or axillary dissection, are allowed.
  13. No metastatic disease (M0, according to TNM staging system).
  14. Available pre-treatment tissue sample (biopsy) material (formalin- fixed paraffin-embedded (FFPE) for central confirmation and RS evaluation by the Assay.
  15. Patients agree to collection of tissue biopsy from the primary breast cancer at the time of study inclusion (screening), at Cycle 1 Day 14 of treatment, and after 24 weeks (surgery), or if experience intolerable side effects, disease progression, or withdraw during 24 weeks of study treatment.
  16. No prior chemotherapy, endocrine, or radiation therapy for current disease.
  17. Adequate organ function:

    1. Hematological: White blood cell (WBC) count ≥ 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5x 109/L, platelet count ≥ 75.0 x109/L, and hemoglobin ≥ 10.0 g/dL (≥ 6.2 mmol/L).
    2. Hepatic: Bilirubin ≤ 1.5 times the upper limit of normal (x ULN) (or total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN in patients with well-documented Gilbert's syndrome); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times ULN.
    3. Renal: Serum creatinine ≤ 1.5 x ULN.
  18. Resolution of all acute toxic effects of prior surgical procedures to grade ≤1 as determined by the NCI CTCAE v.5.0.

Exclusion criteria

Patients will be excluded from the study if they meet ANY of the following criteria:

  1. Metastatic progression (M1, according to TNM staging system).
  2. Substantial nodal involvement (N>2, according to TNM staging system).
  3. Non-large tumor (T0-1, according to TNM staging system).
  4. Bilateral breast carcinoma.
  5. Inflammatory carcinoma (T4d, according to TNM staging system).
  6. Patient with multicentric or multifocal (more than 2 lesions) breast cancer.
  7. Excisional biopsy of the primary tumor.
  8. Known hypersensitivity to any palbociclib excipients.
  9. Known hypersensitivity to any letrozole excipients.
  10. Patients unable to swallow tablets.
  11. Patients have a concurrent malignancy or malignancy within five years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
  12. Previous radiotherapy on the ipsilateral chest wall for the treatment of any other malignancy.
  13. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within four weeks of start of study treatment, or patients who have not recovered from the side effects of any major surgery, or patients that may require major surgery during the course of the study.
  14. Have a serious concomitant systemic disorder (i.e., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator).
  15. Patients with an active bleeding diathesis, previous history of bleeding diathesis, or anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention).
  16. History of malabsorption syndrome or other condition that would interfere with enteral absorption.
  17. Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent (excluding inhaled steroids).
  18. QTc interval > 480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
  19. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (i.e., hypocalcemia, hypokalemia, or hypomagnesemia).
  20. Participation in the treatment phase of an interventional trial within 30 days prior to study treatment start.

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): NCT03819010


Locations
Show Show 18 study locations
Sponsors and Collaborators
MedSIR
Pfizer
Investigators
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Principal Investigator: Antonio Llombart, PdH MedSIR
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Responsible Party: MedSIR
ClinicalTrials.gov Identifier: NCT03819010    
Other Study ID Numbers: MedOPP199
First Posted: January 28, 2019    Key Record Dates
Last Update Posted: February 7, 2020
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 20 hospital will participate at this trial: 17 sites at Spain and 3 at Portugal
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: The trial separate 2 stage: Stage I it will be radomized 26 patients (20 Sites) from January 2019 to June2019 and Stage II: 40 patients (25 sites) from February 2020 to July 2020.
Access Criteria: patient should be randomized od Data base of hospitals

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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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
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
Protein Kinase Inhibitors