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CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer (CIMER)

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: NCT04220476
Recruitment Status : Withdrawn (Initiating a new study with revised Statistics.)
First Posted : January 7, 2020
Last Update Posted : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Tracking Information
First Submitted Date  ICMJE January 3, 2020
First Posted Date  ICMJE January 7, 2020
Last Update Posted Date September 21, 2020
Actual Study Start Date  ICMJE March 4, 2020
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2020)
  • Number of subjects achieving Objective response rate (ORR) will be assessed. [ Time Frame: End of study, up to 36 months. ]
    ORR is defined as the percentage of subjects with either a confirmed complete response (CR) or partial response (PR).
  • Number of Subjects achieving Progression free survival (PFS) [ Time Frame: End of study, up to 36 months. ]
    Progression free survival (PFS) is defined as the time from the start of study treatment until the disease progression or death.
  • Number of subjects achieving Overall survival(OS) will be assessed. [ Time Frame: End of study, up to 36 months. ]
    OS is defined as the time from the start of treatment until death.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2020)
  • Serial levels of Circulating tumor DNA (ctDNA) [ Time Frame: End of study, up to 36 months. ]
    serial levels ctDNA can be an early indication of progression
  • Circulating tumor DNA (ctDNA) levels [ Time Frame: End of study, up to 36 months. ]
    Circulating tumor DNA (ctDNA) levels will be measured to determine baseline cancer heterogeneity and its response to treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer
Official Title  ICMJE CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Radiation: Stereotactic Body Radiation Therapy (SBRT) (50GY in 5 fractions)
    Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT. They will undergo tumor Immunogenic-SBRT(I-SBRT) days 1-12 (+/-2 days, to enable inclusion of holidays). During the week preceding day 1, they will undergo simulation and planning for radiotherapy. Each oligometastatic lesion will be treated with I-SBRT every 48 hours. 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
  • Drug: Letrozole 2.5Mg Tab
    All patients start standard therapy with oral letrozole (Femara), day 1 of the study.
  • Drug: Palbociclib 125mg
    Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT.
Study Arms  ICMJE
  • Active Comparator: ARM 1 - Letrozole and Palbociclib
    Patients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21.
    Interventions:
    • Drug: Letrozole 2.5Mg Tab
    • Drug: Palbociclib 125mg
  • Active Comparator: ARM 2 - Letrozole and Palbociclib + I-SBRT
    Patients 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.
    Interventions:
    • Radiation: Stereotactic Body Radiation Therapy (SBRT) (50GY in 5 fractions)
    • Drug: Letrozole 2.5Mg Tab
    • Drug: Palbociclib 125mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: September 16, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: January 3, 2020)
204
Estimated Study Completion Date  ICMJE December 31, 2028
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT04220476
Other Study ID Numbers  ICMJE 19-09020752
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Weill Medical College of Cornell University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Weill Medical College of Cornell University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Silvia Formenti, M.D. Weill Medical College of Cornell University
PRS Account Weill Medical College of Cornell University
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP