xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05996107</url>
    </required_header>
    <id_info>
      <org_study_id>UMCC 2022.071</org_study_id>
      <secondary_id>HUM00231659</secondary_id>
      <nct_id>NCT05996107</nct_id>
    </id_info>
    <brief_title>Study of Ribociclib Administered Concurrently With Postoperative Radiation Therapy in Patients With High-Risk, Node Positive, HR+/HER2- Breast Cancer</brief_title>
    <official_title>A Phase 1B Study of Ribociclib Administered Concurrently With Postoperative Radiation Therapy in Patients With High-Risk, Node Positive, HR+/HER2- Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Michigan Rogel Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Michigan Rogel Cancer Center</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this research study is to determine the safety, tolerability and dose of&#xD;
        Ribociclib when combined with adjuvant radiation in women with high-risk ER+ breast cancer.&#xD;
  &#xD;
        Once enrolled on study, patients will begin treatment with Ribociclib 400 mg daily at the&#xD;
        same time as they initiate standard of care adjuvant radiation therapy- 50 Gy in 25 fractions&#xD;
        or 42.56 Gy in 16 fractions +/- 10 Gy boost including comprehensive nodal. Paitents will&#xD;
        continue treatment with Ribociclib for up to 6 weeks.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">October 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">October 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Dose limiting toxicity (DLT) of ribociclib administered concurrently with adjuvant RT 1 month post last RT dose</measure>
      <time_frame>up through 30 days after the last dose of study drug or radiotherapy</time_frame>
      <description>Safety evaluations will be based on the incidence, intensity, and type of adverse events, and clinically significant changes in the patient's physical examination, vital signs, and clinical laboratory results. Safety variables will be tabulated and presented for all patients in the study. Exposure to study drug and reasons for discontinuation of study treatment will be tabulated.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of local failure (i.e. local recurrence events)</measure>
      <time_frame>up through 2 years after completion of protocol therapy</time_frame>
      <description>Calculation of follow-up time for all endpoints for patients will begin from the date of diagnosis until documentation of local or regional recurrence for local control, any failure (local, regional, or distant) or death for recurrence-free survival, and death for overall survival.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Local failure-free survival</measure>
      <time_frame>up through 2 years after completion of protocol therapy</time_frame>
      <description>The time from diagnosis date to the first of local or regional recurrence or death. Patients who are alive and free of local regional recurrence at lat follow up will be cencored at that date.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Recurrence-free survival</measure>
      <time_frame>up through 2 years after completion of protocol therapy</time_frame>
      <description>Date of diagnosis until documentation of death. Time-dependent and will be summarized using the Kaplan-Meier method or cumulative incidence method when competing events.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>up through 2 years after completion of protocol therapy</time_frame>
      <description>Overall survival as determined by the date of diagnosis until documentation of death. Time-dependent and will be summarized using the Kaplan-Meier method or cumulative incidence method when competing events.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease free survival</measure>
      <time_frame>up through 2 years after completion of protocol therapy</time_frame>
      <description>Defined as the time to the first of local, regional, or distant recurrence or death</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>RT + Ribociclib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>All patients will be treated with Ribociclib and standard of care radiation therapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ribociclib</intervention_name>
      <description>400 mg daily with a possibly dose reduction to 200 mg daily if required</description>
      <arm_group_label>RT + Ribociclib</arm_group_label>
      <other_name>Kisqali</other_name>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Postoperative Radiation Therapy</intervention_name>
      <description>50 Gy in 25 fractions or 42.56 Gy in 16 fraction +/- 10 Gy boost including comprehensive nodal</description>
      <arm_group_label>RT + Ribociclib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  ER and/or PR-positive (≥ 1% positivity as determined by local pathology laboratory),&#xD;
               HER2-negative breast cancer with &gt; 3 lymph nodes involved on sentinel lymph node&#xD;
               biopsy (SLNB) or axillary lymph node dissection (ALND) OR have between 1-3 lymph nodes&#xD;
               involved AND have T3 disease OR have between 1-3 lymph nodes involved and grade 3&#xD;
               breast cancer.&#xD;
  &#xD;
            -  Age ≥ 18&#xD;
  &#xD;
            -  Patients must have undergone gross total excision of all locoregional disease with&#xD;
               negative margins (i.e. no tumor on ink). At least 21 days must elapse between surgical&#xD;
               treatment for breast cancer and initiation of study treatment.&#xD;
  &#xD;
            -  Patients must have completed chemotherapy (either in neoadjuvant or adjuvant setting).&#xD;
               If received adjuvant chemotherapy, chemotherapy must have completed at least 21 days&#xD;
               prior to initiation of study treatment.&#xD;
  &#xD;
            -  Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and&#xD;
               surgical side effects following definitive breast surgery except for neuropathy and&#xD;
               alopecia&#xD;
  &#xD;
            -  Adequate baseline hematologic, hepatic and renal function as indicated below:&#xD;
  &#xD;
                 -  Patient has adequate bone marrow and organ function as defined by the following&#xD;
                    laboratory values (as assessed by central laboratory for eligibility):&#xD;
  &#xD;
                 -  Absolute neutrophil count ≥ 1.5 × 109/L&#xD;
  &#xD;
                 -  Platelets ≥ 100 × 109/L&#xD;
  &#xD;
                 -  Hemoglobin ≥ 9.0 g/dL&#xD;
  &#xD;
                 -  INR ≤1.5 (unless the patient is receiving anticoagulants and the INR is within&#xD;
                    the therapeutic range of intended use for that anticoagulant within 7 days prior&#xD;
                    to the first dose of study drug)&#xD;
  &#xD;
                 -  Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 according to the&#xD;
                    Modification of Diet in Renal Disease (MDRD) formula&#xD;
  &#xD;
                 -  Total bilirubin &lt; ULN except for patients with Gilbert's syndrome who may only be&#xD;
                    included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN.&#xD;
  &#xD;
                 -  Aspartate transaminase (AST) &lt; 2.5 × ULN, except for patients with liver&#xD;
                    metastasis, who are only included if the AST is &lt; 5 × ULN&#xD;
  &#xD;
                 -  Alanine transaminase (ALT) &lt; 2.5 × ULN, except for patients with liver&#xD;
                    metastasis, who are only included if the ALT is &lt; 5 × ULN&#xD;
  &#xD;
                 -  Patient must have the following laboratory values within normal limits or&#xD;
                    corrected to within normal limits with supplements before the first dose of study&#xD;
                    medication:&#xD;
  &#xD;
                 -  Potassium&#xD;
  &#xD;
                 -  Magnesium&#xD;
  &#xD;
                 -  Total Calcium (corrected for serum albumin)&#xD;
  &#xD;
            -  QTcF interval at screening EKG ≤ 450ms (QT interval using Fridericia's correction).&#xD;
  &#xD;
            -  Mean resting heart rate 50-90 bpm (determined from the EKG).&#xD;
  &#xD;
            -  Ability to swallow study drug (Ribociclib).&#xD;
  &#xD;
            -  ECOG Performance Status 0-1 (Karnofsky &gt; 60%).&#xD;
  &#xD;
            -  Availability of archival tumor tissue from surgical specimen.&#xD;
  &#xD;
            -  Ability to understand and willingness to sign informed consent.&#xD;
  &#xD;
            -  Women of childbearing potential must have confirmed negative pregnancy test (urine or&#xD;
               serum) within 14 days of initiation of study treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior history of radiation therapy to the chest wall and/or regional nodes is not&#xD;
               allowed (but prior radiation therapy to other sites is permissible).&#xD;
  &#xD;
            -  Prior history of CDK4/6 inhibitor therapy.&#xD;
  &#xD;
            -  Patients who are pregnant or breastfeeding.&#xD;
  &#xD;
               • Because radiation is known to be teratogenic, women of childbearing potential must&#xD;
               have a documented negative pregnancy test performed prior to the start of study&#xD;
               therapy (as above) and agree to use adequate contraception (hormonal or double barrier&#xD;
               method of birth control; vasectomized partner; abstinence) prior to study entry and&#xD;
               for the duration of study participation. Should a woman become pregnant or suspect she&#xD;
               is pregnant while participating in this study, she should inform her treating&#xD;
               physician immediately.&#xD;
  &#xD;
            -  Patient with distant metastases of breast cancer beyond regional lymph nodes and/or&#xD;
               evidence of breast cancer recurrence prior to study enrollment.&#xD;
  &#xD;
            -  Clinically significant, uncontrolled heart disease and/or cardiac repolarization&#xD;
               abnormality, including any of the following:&#xD;
  &#xD;
                 -  History of documented myocardial infarction (MI), angina pectoris, symptomatic&#xD;
                    pericarditis, or coronary artery bypass graft within 6 months prior to trial&#xD;
                    entry.&#xD;
  &#xD;
                 -  Documented cardiomyopathy.&#xD;
  &#xD;
                 -  Left Ventricular Ejection Fraction (LVEF) &lt; 50% as determined by Multiple Gated&#xD;
                    acquisition (MUGA) scan or echocardiogram (ECHO) (testing not mandatory)&#xD;
  &#xD;
                 -  Long QT syndrome or family history of idiopathic sudden death or congenital long&#xD;
                    QT syndrome, or any of the following:&#xD;
  &#xD;
                 -  Risk factors for Torsades de Pointes (TdP) including uncorrected hypocalcemia,&#xD;
                    hypokalemia or hypomagnesemia, history of cardiac failure, or history of&#xD;
                    clinically significant/symptomatic bradycardia.&#xD;
  &#xD;
                 -  Concomitant medication(s) with a known risk to prolong the QT interval and/or&#xD;
                    known to cause TdP that cannot be discontinued or replaced by safe alternative&#xD;
                    medication (e.g. within 5 half-lives or 7 days prior to starting trial&#xD;
                    treatment).&#xD;
  &#xD;
                 -  Inability to determine the QTcF interval.&#xD;
  &#xD;
                 -  Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia),&#xD;
                    complete left bundle branch block, high-grade Atrioventricular (AV) block (e.g.&#xD;
                    bifascicular block, Mobitz type II and third degree AV block).&#xD;
  &#xD;
                 -  Uncontrolled arterial hypertension with systolic blood pressure &gt; 160 mmHg.&#xD;
  &#xD;
            -  Patient has any other concurrent severe and/or uncontrolled medical condition that&#xD;
               would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate&#xD;
               patient participation in the clinical trial or compromise compliance with the protocol&#xD;
               (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other&#xD;
               significant liver disease, active untreated or uncontrolled fungal, bacterial or viral&#xD;
               infections, active infection requiring systemic antibacterial therapy, etc.) or limit&#xD;
               life expectancy to ≤5 years. Questions regarding inclusion of individual subjects&#xD;
               should be directed to Drs. Cobain and Speers (ecobain@med.umich.edu and&#xD;
               cspeers@med.umich.edu).&#xD;
  &#xD;
            -  Patient has a concurrent invasive malignancy or a prior invasive malignancy whose&#xD;
               treatment was completed within 2 years before randomization. Note: Patients with&#xD;
               adequately treated, basal or squamous cell skin carcinoma or curatively resected&#xD;
               cervical cancer in situ are eligible.&#xD;
  &#xD;
            -  Patient has impairment of gastrointestinal (GI) function or GI disease that may&#xD;
               significantly alter the absorption of the oral trial treatments (e.g. uncontrolled&#xD;
               ulcerative diseases, uncontrolled nausea, vomiting or diarrhea, malabsorption&#xD;
               syndrome, or small bowel resection).&#xD;
  &#xD;
            -  Patients must not receive any additional anti-cancer therapy or investigational agents&#xD;
               during study therapy. Anti-cancer therapies include chemotherapy and endocrine&#xD;
               therapy.&#xD;
  &#xD;
            -  Patient is currently receiving any of the following substances within 7 days before&#xD;
               randomization:&#xD;
  &#xD;
                 -  Concomitant medications, herbal supplements, and/or fruits (e.g. grapefruit,&#xD;
                    pummellos, starfruit, Seville oranges) and their juices that are known as strong&#xD;
                    inhibitors or inducers of CYP3A4/5.&#xD;
  &#xD;
                 -  Medications that have a narrow therapeutic window and are predominantly&#xD;
                    metabolized through CYP3A4/5.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Erin Cobain, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Michigan Rogel Cancer Center</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Corey Speers, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Michigan Rogel Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Cancer AnswerLine</last_name>
      <phone>1-800-865-1125</phone>
      <email>CancerAnswerLine@med.umich.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of Michigan</name>
        <address>
          <city>Ann Arbor</city>
          <state>Michigan</state>
          <zip>48109</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HR+/HER2-</keyword>
    <keyword>Node positive</keyword>
    <keyword>High-Risk breast cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05996107
  org study id: UMCC 2022.071
  secondary id: HUM00231659
  nct id: NCT05996107
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this research study is to determine the safety, tolerability and dose of
        Ribociclib when combined with adjuvant radiation in women with high-risk ER+ breast cancer.
  
        Once enrolled on study, patients will begin treatment with Ribociclib 400 mg daily at the
        same time as they initiate standard of care adjuvant radiation therapy- 50 Gy in 25 fractions
        or 42.56 Gy in 16 fractions +/- 10 Gy boost including comprehensive nodal. Paitents will
        continue treatment with Ribociclib for up to 6 weeks.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose limiting toxicity (DLT) of ribociclib administered concurrently with adjuvant RT 1 month post last RT dose
  time frame: up through 30 days after the last dose of study drug or radiotherapy
  description: Safety evaluations will be based on the incidence, intensity, and type of adverse events, and clinically significant changes in the patient's physical examination, vital signs, and clinical laboratory results. Safety variables will be tabulated and presented for all patients in the study. Exposure to study drug and reasons for discontinuation of study treatment will be tabulated.
  measure: Cumulative incidence of local failure (i.e. local recurrence events)
  time frame: up through 2 years after completion of protocol therapy
  description: Calculation of follow-up time for all endpoints for patients will begin from the date of diagnosis until documentation of local or regional recurrence for local control, any failure (local, regional, or distant) or death for recurrence-free survival, and death for overall survival.
  measure: Local failure-free survival
  time frame: up through 2 years after completion of protocol therapy
  description: The time from diagnosis date to the first of local or regional recurrence or death. Patients who are alive and free of local regional recurrence at lat follow up will be cencored at that date.
  measure: Recurrence-free survival
  time frame: up through 2 years after completion of protocol therapy
  description: Date of diagnosis until documentation of death. Time-dependent and will be summarized using the Kaplan-Meier method or cumulative incidence method when competing events.
  measure: Overall survival
  time frame: up through 2 years after completion of protocol therapy
  description: Overall survival as determined by the date of diagnosis until documentation of death. Time-dependent and will be summarized using the Kaplan-Meier method or cumulative incidence method when competing events.
  measure: Disease free survival
  time frame: up through 2 years after completion of protocol therapy
  description: Defined as the time to the first of local, regional, or distant recurrence or death
  arm group label: RT + Ribociclib
  arm group type: Experimental
  description: All patients will be treated with Ribociclib and standard of care radiation therapy
  intervention type: Drug
  intervention name: Ribociclib
  description: 400 mg daily with a possibly dose reduction to 200 mg daily if required
  arm group label: RT + Ribociclib
  other name: Kisqali
  intervention type: Radiation
  intervention name: Postoperative Radiation Therapy
  description: 50 Gy in 25 fractions or 42.56 Gy in 16 fraction +/- 10 Gy boost including comprehensive nodal
  arm group label: RT + Ribociclib
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Erin Cobain, MD
  role: Principal Investigator
  affiliation: University of Michigan Rogel Cancer Center
  last name: Corey Speers, MD, PhD
  role: Principal Investigator
  affiliation: University of Michigan Rogel Cancer Center
  last name: Cancer AnswerLine
  phone: 1-800-865-1125
  email: CancerAnswerLine@med.umich.edu
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  sharing ipd: No