Clinical Trials /

CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer

NCT04220476

Description:

Women with Hormone Receptor (HR)+ Human Epidermal growth factor Receptor (HER)2- metastatic breast cancer are eligible to a randomized trial. Patients receiving standard first line therapy for metastatic HR+ Breast cancer(BC) (letrozole+palbociclib) are randomly assigned to also receive Stereotactic Body Radiation Therapy(SBRT) to each metastatic lesion.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer
  • Official Title: CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-09020752
  • NCT ID: NCT04220476

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Letrozole 2.5Mg TabARM 1 - Letrozole and Palbociclib
Palbociclib 125mgARM 1 - Letrozole and Palbociclib

Purpose

Women with Hormone Receptor (HR)+ Human Epidermal growth factor Receptor (HER)2- metastatic breast cancer are eligible to a randomized trial. Patients receiving standard first line therapy for metastatic HR+ Breast cancer(BC) (letrozole+palbociclib) are randomly assigned to also receive Stereotactic Body Radiation Therapy(SBRT) to each metastatic lesion.

Trial Arms

NameTypeDescriptionInterventions
ARM 1 - Letrozole and PalbociclibActive ComparatorPatients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21.
  • Letrozole 2.5Mg Tab
  • Palbociclib 125mg
ARM 2 - Letrozole and Palbociclib + I-SBRTActive ComparatorPatients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT. Treatment may be given daily (to keep the total I-SBRT treatment time to ≤ 12 days) and lesions targeted with I-SBRT will thus be alternated each day to accommodate for the 48 hour interval between fractions.
  • Letrozole 2.5Mg Tab
  • Palbociclib 125mg

Eligibility Criteria

        Inclusion Criteria:

          -  Female ≥ 18 years of age pre and post-menopausal

          -  Oligometastatic disease (≤ 5 sites of disease)

          -  Premenopausal status is defined as either:

          -  Patient had last menstrual period within the last 12 months, OR

          -  If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must
             be in the premenopausal range per local normal range, OR

          -  In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the
             premenopausal range per local normal range.

          -  Patients who have undergone bilateral oophorectomy are eligible.

          -  Post-menopausal status defined as either 1) at least 2 years without menstrual period
             or 2) patients older than 50 with serological evidence of post-menopausal status or 3)
             hysterectomized patients of any age with FSH confirmation of post-menopausal status.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Biopsy proven diagnosis of HR+HER2- metastatic breast cancer. ER expression is >10%

          -  Patient needs to be able to understand and demonstrate willingness to sign a written
             informed consent document

          -  Hematological WBC ≥ 2000/uL

          -  Absolute neutrophil count (ANC) ≥1500/µL

          -  Platelets ≥100 000/µL

          -  Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Renal Creatinine OR Measured or calculated
             creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN
             OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN

        Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
        bilirubin levels >1.5 × ULN

          -  AST (SGOT) and ALT (SGPT) ≤2.5 × ULN

          -  Coagulation International normalized ratio (INR) OR prothrombin time (PT)

          -  Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is
             receiving anticoagulant therapy if PT or aPTT is within therapeutic range of intended
             use of anticoagulants

        Exclusion Criteria:

          -  Active connective tissue disorders, such as lupus or scleroderma requiring flare
             therapy

          -  Current use of systemic chemotherapy, endocrine therapy or HER2-neu targeted therapy

          -  Male breast cancer patients

          -  Any lesion >5 cm in greatest diameter.

          -  Inability to obtain histologic proof of metastatic breast cancer

          -  Has received previous endocrine or chemotherapy for metastatic breast cancer.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

          -  Has a known additional malignancy (second primary) that is progressing or has required
             active treatment within the past 3 years. Note: - - - Participants with basal cell
             carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g.
             cervical cancer in situ) that have undergone potentially curative therapy are not
             excluded.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has an active infection requiring systemic therapy. Has a known history of Human
             Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by
             local health authority.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Patients with uncontrolled brain metastases
      
Maximum Eligible Age:90 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects achieving Objective response rate (ORR) will be assessed.
Time Frame:End of study, up to 36 months.
Safety Issue:
Description:ORR is defined as the percentage of subjects with either a confirmed complete response (CR) or partial response (PR).

Secondary Outcome Measures

Measure:Serial levels of Circulating tumor DNA (ctDNA)
Time Frame:End of study, up to 36 months.
Safety Issue:
Description:serial levels ctDNA can be an early indication of progression
Measure:Circulating tumor DNA (ctDNA) levels
Time Frame:End of study, up to 36 months.
Safety Issue:
Description:Circulating tumor DNA (ctDNA) levels will be measured to determine baseline cancer heterogeneity and its response to treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Weill Medical College of Cornell University

Trial Keywords

  • metastatic Breast cancer
  • HR+HER2-
  • HR + BC
  • SBRT

Last Updated

January 3, 2020