<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/NCT03784677</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0680</org_study_id>
    <secondary_id>NCI-2018-02835</secondary_id>
    <secondary_id>2018-0680</secondary_id>
    <nct_id>NCT03784677</nct_id>
  </id_info>
  <brief_title>A Phase I Study of SOR-C13 in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase I Study of SOR-C13 in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</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>
      This phase I trial studies the side effects and best dose of SOR-C13 in treating patients&#xD;
      with solid tumors that have spread to other places in the body (advanced) and does not&#xD;
      respond to treatment. Drugs used in chemotherapy, such as SOR-C13, work in different ways to&#xD;
      stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,&#xD;
      or by stopping them from spreading.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To define the maximum tolerated doses (MTD) of TRPV6 calcium channel inhibitor SOR-C13&#xD;
      (SOR-C13) in subjects with advanced solid tumor cancers of epithelial origin.&#xD;
&#xD;
      II. To define the safety profiles of the treatment.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate clinical response signals to the treatment. II. To assess predictive&#xD;
      biomarkers (baseline molecular mutation status) and/or resistant pathways by comparing&#xD;
      molecular signatures at baseline versus at time of relapse in patients who have achieved&#xD;
      objective responses.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study.&#xD;
&#xD;
      Patients receive TRPV6 calcium channel inhibitor SOR-C13 intravenously (IV) over 2 hours on&#xD;
      days 1, 2, 8, 9, 15, 16, 22, and 23. Cycles repeat every 28 days in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 29, 2019</start_date>
  <completion_date type="Actual">June 20, 2023</completion_date>
  <primary_completion_date type="Actual">June 20, 2023</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>Incidence of adverse events and serious adverse events</measure>
    <time_frame>Up to 30 days after last dose</time_frame>
    <description>Will assess clinical symptoms and laboratory values, evaluate vital signs and perform physical exams, with a special attention to treatment- related fatigue, gastrointestinal (GI) symptoms, cardiovascular events, myelosuppression, and neurotoxicity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of &gt;= grade 2 adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</measure>
    <time_frame>Up to 30 days after last dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose-limiting toxicities</measure>
    <time_frame>Up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Withdrawals from the study due to treatment-related adverse events will be documented</measure>
    <time_frame>Up to 30 days after last dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of the treatment regimen such as dose delay and dose reduction over time by dose level due to treatment-related adverse events</measure>
    <time_frame>Up to 30 days after last dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective responses</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Defined as complete response(CR)s and partial response (PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Defined as stable disease (SD)/CR/PR according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive biomarkers</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Fisher exact test is used to associate potential biomarkers with SD &gt;= 6 months/CR/PR. Next generation sequencing for targeted exome panel and NanoString arrays are used to reveal potential biomarkers of acquired resistance.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Advanced Malignant Solid Neoplasm</condition>
  <condition>Refractory Malignant Solid Neoplasm</condition>
  <condition>Refractory Ovarian Carcinoma</condition>
  <condition>Refractory Pancreatic Carcinoma</condition>
  <condition>Stage II Pancreatic Cancer AJCC v8</condition>
  <condition>Stage IIA Pancreatic Cancer AJCC v8</condition>
  <condition>Stage IIB Pancreatic Cancer AJCC v8</condition>
  <condition>Stage III Ovarian Cancer AJCC v8</condition>
  <condition>Stage III Pancreatic Cancer AJCC v8</condition>
  <condition>Stage III Prostate Cancer AJCC v8</condition>
  <condition>Stage IIIA Ovarian Cancer AJCC v8</condition>
  <condition>Stage IIIA Prostate Cancer AJCC v8</condition>
  <condition>Stage IIIB Ovarian Cancer AJCC v8</condition>
  <condition>Stage IIIB Prostate Cancer AJCC v8</condition>
  <condition>Stage IIIC Ovarian Cancer AJCC v8</condition>
  <condition>Stage IIIC Prostate Cancer AJCC v8</condition>
  <condition>Stage IV Ovarian Cancer AJCC v8</condition>
  <condition>Stage IV Pancreatic Cancer AJCC v8</condition>
  <condition>Stage IV Prostate Cancer AJCC v8</condition>
  <condition>Stage IVA Ovarian Cancer AJCC v8</condition>
  <condition>Stage IVA Prostate Cancer AJCC v8</condition>
  <condition>Stage IVB Ovarian Cancer AJCC v8</condition>
  <condition>Stage IVB Prostate Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Treatment (TRPV6 calcium channel inhibitor SOR-C13)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive TRPV6 calcium channel inhibitor SOR-C13 IV over 2 hours on days 1, 2, 8, 9, 15, 16, 22, and 23. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TRPV6 Calcium Channel Inhibitor SOR-C13</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (TRPV6 calcium channel inhibitor SOR-C13)</arm_group_label>
    <other_name>SOR-C13</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        To be eligible for this trial, patients must meet all of the following eligibility&#xD;
        criteria.&#xD;
&#xD;
          1. Subjects with a histologic diagnosis of solid tumor cancers of epithelial origin&#xD;
             (metastatic epithelial ovarian, pancreatic and prostate cancers are preferred since&#xD;
             these tumor types have TRPV6 overexpression).&#xD;
&#xD;
          2. Subjects with advanced refractory cancer for which standard curative or palliative&#xD;
             measures do not exist or are no longer effective. There is no limitation on the number&#xD;
             or types of prior therapy.&#xD;
&#xD;
          3. Patients must have measurable or evaluable disease, as defined by Response Evaluation&#xD;
             Criteria in Solid Tumors 1.1 (RECIST1.1).&#xD;
&#xD;
          4. Men or women aged ≥ 18 years.&#xD;
&#xD;
          5. Women of child-bearing potential (who are not postmenopausal for at least one year or&#xD;
             are not surgically sterile) and men must agree to use adequate contraception (e.g.,&#xD;
             hormonal, barrier device, or abstinence) prior to study entry, for the duration of&#xD;
             study participation, and for 30 days after the last dose the study agents.&#xD;
&#xD;
          6. Patients must have an ECOG performance status of 0 to 1.&#xD;
&#xD;
          7. Patients must have adequate organ functions as defined below:&#xD;
&#xD;
               -  Neutrophils ≥ 1,500 /L&#xD;
&#xD;
               -  Platelets ≥ 100,000 /L&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x ULN (upper limit of normal) (except patients with&#xD;
                  Gilbert's syndrome, who must have a total bilirubin ≤ 3.0 mg/dL)&#xD;
&#xD;
               -  ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases persist&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 45 mL/minute by&#xD;
                  the Cockcroft-Gault method&#xD;
&#xD;
               -  Albumin ≥ 3.0 g/dL (≥30 g/L)&#xD;
&#xD;
               -  INR (international normalized ratio) ≤1.4&#xD;
&#xD;
          8. Patients should be able to read and fully understand the requirements of the trial, be&#xD;
             willing to comply with all trial visits and assessments, and be willing and able to&#xD;
             sign an IRB-approved written informed consent document.&#xD;
&#xD;
          9. Subjects must have recovered from major infections and/or surgical procedures and, in&#xD;
             the opinion of the investigator, not have a significant active concurrent medical&#xD;
             illness precluding protocol treatment.&#xD;
&#xD;
         10. Patients agree to provide archival tissue block or 10 formalin-fixed paraffin-embedded&#xD;
             (FFPE) slides paraffin for use in pharmacodynamics correlative studies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients who meet any of the following criteria will be not eligible for the study.&#xD;
&#xD;
          1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection requiring intravenous antibiotics, symptomatic congestive heart failure&#xD;
             (NYHA Class III or IV), or history of myocardial infarction, unstable angina, stroke&#xD;
             or transient ischemic attack within 6 months prior to study enrollment.&#xD;
&#xD;
          2. History of clinically significant allergic reactions to the study drugs or their&#xD;
             analogs, or any component of the products.&#xD;
&#xD;
          3. Any treatment specific for systemic tumor control within 3 weeks prior to the&#xD;
             initiation of the study drugs; or within 2 weeks if cytotoxic agents were given weekly&#xD;
             (within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targeted&#xD;
             agents with half-lives and pharmacodynamic effects lasting less than 4 days, or&#xD;
             failure to recover from toxic effects of any therapy prior to the study drug&#xD;
             treatment.&#xD;
&#xD;
          4. Patients who have not recovered from major surgical procedure, or significant&#xD;
             traumatic injury (i.e., still need additional medical care for these issues).&#xD;
&#xD;
          5. History of any of the following cardiovascular events or conditions within the past 6&#xD;
             months prior to enrolment: myocardial infarction, unstable angina, cerebrovascular&#xD;
             accident or transient ischemic attack, New York Heart Association Class ≥ II chronic&#xD;
             heart failure, significant arrhythmia*; QTcF interval &gt;430 msec or use of drugs that&#xD;
             prolong the QT interval at screening; family history of long QT syndrome.&#xD;
&#xD;
             *Significant arrhythmias are defined as symptoms of syncope or severe palpitations&#xD;
             (palpitations requiring referral to cardiac monitoring), or ECG findings of&#xD;
             supraventricular tachycardia (including atrial fibrillation or atrial flutter) or&#xD;
             ventricular tachycardia (including ventricular fibrillation) or ventricular ectopy&#xD;
             (ventricular premature depolarization)&#xD;
&#xD;
          6. Clinically significant and uncontrolled major medical condition(s) that places the&#xD;
             subject at an unacceptably high risk for toxicities. These include, but are not&#xD;
             limited to: active infections, symptomatic pulmonary disease, inadequate pulmonary&#xD;
             function, seizure disorder, or psychiatric illness.&#xD;
&#xD;
          7. Current use of more than one antihypertensive medication.&#xD;
&#xD;
          8. For patients receiving antihypertensive medication: systolic blood pressure &lt;120 mm Hg&#xD;
             and/or diastolic blood pressure &lt;70 mm Hg at screening.&#xD;
&#xD;
          9. Major surgical procedure within 4 weeks prior to enrolment.&#xD;
&#xD;
         10. Lactating or pregnant female.&#xD;
&#xD;
         11. Females of childbearing potential and males not using adequate birth control.&#xD;
&#xD;
         12. Current treatment or treatment within 4 weeks of screening with bisphosphonates.&#xD;
&#xD;
         13. Hypocalcemia at screening.&#xD;
&#xD;
         14. History of acute pancreatitis within 6 months prior to screening.&#xD;
&#xD;
         15. Known hypoparathyroidism, pseudohypoparathyroidism, or vitamin D deficiency, or&#xD;
             clinical evidence of other conditions known to associated with hypocalcemia, including&#xD;
             hypoalbuminemia, hyperphosphatemia, hypomagnesemia.&#xD;
&#xD;
         16. Current treatment or treatment within 4 weeks of screening with drugs known to reduce&#xD;
             serum calcium levels, including: bisphosphonates, antiepileptic drugs, cinacalcet,&#xD;
             macrolide antibiotics (such as erythromycin, azithromycin), large doses of&#xD;
             corticosteroids (&gt;20 mg/day of prednisone or equivalent), or any IV use of&#xD;
             corticosteroids. In addition, long-term use (defined as ongoing use for ≥4 weeks) of&#xD;
             corticosteroids within 8 weeks of screening is prohibited.&#xD;
&#xD;
         17. Symptomatic and uncontrolled metastasis to the central nervous system or&#xD;
             leptomeningeal or lymphangitic carcinomatosis.&#xD;
&#xD;
         18. Grade 2 or higher peripheral neuropathy.&#xD;
&#xD;
         19. Human immunodeficiency virus requiring HAART treatment due to unknown drug-drug&#xD;
             interactions or known active hepatitis B or C.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Siqing Fu</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>M D Anderson Cancer Center</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>June 22, 2023</last_update_submitted>
  <last_update_submitted_qc>June 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>SOR-C13</mesh_term>
    <mesh_term>Calcium</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03784677
org study id: 2018-0680
secondary id: NCI-2018-02835
secondary id: 2018-0680
nct id: NCT03784677
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of SOR-C13 in treating patients
      with solid tumors that have spread to other places in the body (advanced) and does not
      respond to treatment. Drugs used in chemotherapy, such as SOR-C13, work in different ways to
      stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,
      or by stopping them from spreading.
PRIMARY OBJECTIVES:

      I. To define the maximum tolerated doses (MTD) of TRPV6 calcium channel inhibitor SOR-C13
      (SOR-C13) in subjects with advanced solid tumor cancers of epithelial origin.

      II. To define the safety profiles of the treatment.

      SECONDARY OBJECTIVES:

      I. To evaluate clinical response signals to the treatment. II. To assess predictive
      biomarkers (baseline molecular mutation status) and/or resistant pathways by comparing
      molecular signatures at baseline versus at time of relapse in patients who have achieved
      objective responses.

      OUTLINE: This is a dose-escalation study.

      Patients receive TRPV6 calcium channel inhibitor SOR-C13 intravenously (IV) over 2 hours on
      days 1, 2, 8, 9, 15, 16, 22, and 23. Cycles repeat every 28 days in the absence of disease
      progression or unacceptable toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events and serious adverse events
time frame: Up to 30 days after last dose
description: Will assess clinical symptoms and laboratory values, evaluate vital signs and perform physical exams, with a special attention to treatment- related fatigue, gastrointestinal (GI) symptoms, cardiovascular events, myelosuppression, and neurotoxicity.
measure: Incidence of >= grade 2 adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
time frame: Up to 30 days after last dose
measure: Dose-limiting toxicities
time frame: Up to 28 days
measure: Withdrawals from the study due to treatment-related adverse events will be documented
time frame: Up to 30 days after last dose
measure: Change of the treatment regimen such as dose delay and dose reduction over time by dose level due to treatment-related adverse events
time frame: Up to 30 days after last dose
measure: Objective responses
time frame: Up to 6 months
description: Defined as complete response(CR)s and partial response (PR).
measure: Clinical benefit
time frame: Up to 6 months
description: Defined as stable disease (SD)/CR/PR according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
measure: Predictive biomarkers
time frame: Up to 6 months
description: Fisher exact test is used to associate potential biomarkers with SD >= 6 months/CR/PR. Next generation sequencing for targeted exome panel and NanoString arrays are used to reveal potential biomarkers of acquired resistance.
arm group label: Treatment (TRPV6 calcium channel inhibitor SOR-C13)
arm group type: Experimental
description: Patients receive TRPV6 calcium channel inhibitor SOR-C13 IV over 2 hours on days 1, 2, 8, 9, 15, 16, 22, and 23. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: TRPV6 Calcium Channel Inhibitor SOR-C13
description: Given IV
arm group label: Treatment (TRPV6 calcium channel inhibitor SOR-C13)
other name: SOR-C13
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Siqing Fu
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: M D Anderson Cancer Center
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Prostatic Neoplasms
mesh term: Neoplasms
mesh term: Pancreatic Neoplasms
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: SOR-C13
mesh term: Calcium