<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/NCT03308396</url>
  </required_header>
  <id_info>
    <org_study_id>BTCRC-GU16-043</org_study_id>
    <nct_id>NCT03308396</nct_id>
  </id_info>
  <brief_title>Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer</brief_title>
  <official_title>Single Arm Phase Ib/II Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer: Big Ten Cancer Research Consortium BTCRC-GU16-043</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ajjai Alva, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Big Ten Cancer Research Consortium</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Big Ten Cancer Research Consortium</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 is a single arm, multi-centre (via Big Ten Cancer Research Consortium) phase Ib/II study&#xD;
      of patients treated with durvalumab 1500 mg IV q 4 weeks in combination with guadecitabine at&#xD;
      the recommended phase 2 dose subcutaneously for 5 consecutive days. Eligible patients will&#xD;
      have metastatic RCC with a clear cell component, ECOG performance status of 0-1, have&#xD;
      received 0-1 prior therapy but no prior anti-PD-1/PD-L1/CTLA4 (Cohort 1, 36 subjects). Study&#xD;
      treatment could potentially continue for up to 13 cycles (52 weeks).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of up to 58 subjects will be enrolled on both phases.&#xD;
&#xD;
      Phase Ib: 6-12 subjects; enrolled into either Cohort 1 or 2. Phase II: 46 subjects; enrolled&#xD;
      into either Cohort 1 or 2.&#xD;
&#xD;
      Cohort 1 (36 subjects): received 0-1 prior therapy and no prior anti-PD-1/PD-L1/CTLA4.&#xD;
&#xD;
      Cohort 2 (16 subjects): received up to 2 prior therapies, one of which must include an&#xD;
      anti-PD-1/PD-L1 therapy to which they did not respond. Only one prior anti-PD-1/PD-L1 therapy&#xD;
      is allowed.&#xD;
&#xD;
      Patients from Phase Ib treated at the eventual phase II dose will be combined with patients&#xD;
      in Phase II in the efficacy analysis.&#xD;
&#xD;
        -  Therapy will start with guadecitabine on days 1-5 of a 28-day cycle. Guadecitabine will&#xD;
           be dosed subcutaneously on days 1-5 at either dose level 0 (60 mg/m2) or dose level -1&#xD;
           (45 mg/m2), based on the recommended phase II dose.&#xD;
&#xD;
        -  Durvalumab will be started on day 8 of the 28-day cycle. Durvalumab will be administered&#xD;
           intravenously at a flat dose of 1500mg every 28 days.&#xD;
&#xD;
        -  Study treatment may continue for up to 13 cycles (52 weeks) in the absence of confirmed&#xD;
           progression, intolerable toxicity, or withdrawal of consent.&#xD;
&#xD;
      Phase Ib Treatment Plan&#xD;
&#xD;
        -  Dose limiting toxicities (DLTs) will be evaluated within the first cycle (i.e., within&#xD;
           the first 28 days).&#xD;
&#xD;
        -  Six patients will be enrolled at dose level 0. If 2 or fewer patients experience a dose&#xD;
           limiting toxicity, the study will continue to the phase II portion at dose level 0.&#xD;
&#xD;
        -  Alternately, if 3 or more patients have a dose limiting toxicity at dose level 0, 6&#xD;
           patients will be accrued at the lower dose (dose -1). If 2 or fewer patients experience&#xD;
           a dose limiting toxicity, the study will continue to phase II at dose level -1.&#xD;
&#xD;
        -  If 3 or more subjects experience a dose limiting toxicity at dose level -1, the&#xD;
           treatment will be considered unsafe and the trial will be stopped. In this case,&#xD;
           durvalumab and guadecitabine will be permanently discontinued and the subjects followed&#xD;
           per protocol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 19, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</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>
    <intervention_model_description>Phase Ib/II</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open-label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Phase Ib: Dose limiting toxicities will be assessed to determine if the trial is stopped before the Phase II portion.</measure>
    <time_frame>28 days/First cycle</time_frame>
    <description>Number of patients with dose-limiting toxicity (DLT) of the combination of durvalumab and guadecitabine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>1 year</time_frame>
    <description>Objective response rate (complete response (CR) + partial response (PR)) by RECIST 1.1 in Cohort 1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase II: Overall Survival (OS)</measure>
    <time_frame>2 years</time_frame>
    <description>will be reported with 95% confidence intervals from the Kaplan-Meier estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Duration of Response (DoR)</measure>
    <time_frame>2 years</time_frame>
    <description>will be assessed using Kaplan-Meier estimates including the 95% confidence band separately for cohort 1 and for cohort 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Progression-free survival (PFS)</measure>
    <time_frame>2 years</time_frame>
    <description>will be assessed using Kaplan-Meier estimates including the 95% confidence band separately for cohort 1 and for cohort 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Clinical benefit rate (CBR)</measure>
    <time_frame>2 years</time_frame>
    <description>reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Complete response (CR) proportion</measure>
    <time_frame>2 years</time_frame>
    <description>reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Objective Response Rate (ORR)</measure>
    <time_frame>2 years</time_frame>
    <description>reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Assess Adverse Events</measure>
    <time_frame>2 years</time_frame>
    <description>by CTCAE ver 4 including events of special interest such as immune mediated toxicities</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Advanced Kidney Cancer</condition>
  <condition>Kidney Cancer</condition>
  <condition>Clear Cell Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is a non-randomized, single arm, open label Phase Ib/II study.&#xD;
Phase Ib:&#xD;
Days 1-5&#xD;
Guadecitabine:&#xD;
Dose 0: 60 mg/m^2&#xD;
Dose -1: 45 mg/m^2&#xD;
Phase II:&#xD;
Days 1-5 Guadecitabine (at Ph II dose)&#xD;
Day 8 Durvalumab (1500 mg IV) Day 8 Durvalumab (1500 mg IV)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Guadecitabine</intervention_name>
    <description>Days 1-5 Dose 0: 60 mg/m^2 Dose -1: 45 mg/m^2</description>
    <arm_group_label>Single Arm</arm_group_label>
    <other_name>SGI-110</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Day 8 Durvalumab (1500 mg IV)</description>
    <arm_group_label>Single Arm</arm_group_label>
    <other_name>MEDI4736</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subject must meet all of the following applicable inclusion criteria to participate in this&#xD;
        study:&#xD;
&#xD;
          -  Written informed consent and HIPAA authorization for release of personal health&#xD;
             information.&#xD;
&#xD;
          -  ECOG Performance Status 0-1 within 28 days prior to registration.&#xD;
&#xD;
          -  Histological diagnosis of clear cell renal cell carcinoma (pure or mixed) with&#xD;
             radiologic or histologic evidence of metastatic disease.&#xD;
&#xD;
          -  At least 1 lesion, not previously irradiated that can be accurately measured at&#xD;
             baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have a&#xD;
             short axis ≥ 15mm) with a computed tomography (CT) or magnetic resonance imaging (MRI)&#xD;
             and that is suitable for accurate repeated measurements as per Response Evaluation&#xD;
             Criteria in Solid Tumors, version 1.1 (RECIST 1.1) guidelines.&#xD;
&#xD;
          -  For cohort 1, subjects may have received up to 1 and no more than 1 prior line of&#xD;
             systemic therapy (not counting any neoadjuvant/adjuvant therapy) including anti-VEGF,&#xD;
             VEGFR inhibitor, MET inhibitor or mTOR inhibitor for metastatic disease. They cannot&#xD;
             have received any prior anti-PD-1/PD-L1/CTLA4 therapy including durvalumab.&#xD;
&#xD;
          -  For cohort 2, subjects may have received up to 2 prior systemic therapies which should&#xD;
             include 1 (and only 1) prior anti-PD-1/PD-L1 therapy but did not have an objective&#xD;
             response to the prior anti-PD-1/Pd-L1 therapy. The treating investigator must document&#xD;
             that the patient did not have an objective response to prior anti-PD-1/PD-L1 therapy.&#xD;
             They may have received prior anti-CTLA4 therapy.&#xD;
&#xD;
          -  Subjects may not have had radiotherapy treatment to more than 30% of the bone marrow&#xD;
             or with a wide field of radiation within 4 weeks of the first dose of study drug.&#xD;
&#xD;
          -  Prior cancer treatment must be completed at least 14 days prior to study registration&#xD;
             and the subject must have recovered from all reversible acute toxic effects of the&#xD;
             regimen (other than alopecia) to ≤Grade 1 or baseline.&#xD;
&#xD;
          -  Demonstrate adequate organ function as defined in the table below; all screening labs&#xD;
             to be obtained within 28 days prior to registration:&#xD;
&#xD;
        Hematological:&#xD;
&#xD;
          -  White blood cell (WBC) ≥ 3 K/mm^3&#xD;
&#xD;
          -  Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm^3&#xD;
&#xD;
          -  Hemoglobin (Hgb) ≥ 9 g/dL&#xD;
&#xD;
          -  Platelets (Plt) ≥ 100,000/mm^3&#xD;
&#xD;
        Renal:&#xD;
&#xD;
          -  Calculated creatinine clearance ≥ 40 cc/min using the Cockcroft-Gault formula&#xD;
&#xD;
        Hepatic:&#xD;
&#xD;
          -  Total Bilirubin ≤ 1.5 × upper limit of normal (ULN), except in cases of Gilbert's&#xD;
             syndrome where the criteria will be ≤ 5 x ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) ≤ 2.5 × ULN&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) ≤ 2.5 × ULN&#xD;
&#xD;
               -  Females of childbearing potential must have a negative serum pregnancy test&#xD;
                  within 28 days prior to registration.&#xD;
&#xD;
               -  Females of childbearing potential and males must be willing to abstain from&#xD;
                  heterosexual activity or to use at least 1 highly effective methods of&#xD;
                  contraception from the time of informed consent until 30 days after treatment&#xD;
                  discontinuation. The two contraception methods can be comprised of two barrier&#xD;
                  methods, or a barrier method plus a hormonal method.&#xD;
&#xD;
               -  Life expectancy ≥ 12 weeks (in the opinion of the Investigator)&#xD;
&#xD;
               -  Body weight &gt;30kg&#xD;
&#xD;
               -  Subject is willing and able to comply with the protocol for the duration of the&#xD;
                  study including undergoing treatment and scheduled visits and examinations&#xD;
                  including follow up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects meeting any of the criteria below may not participate in the study:&#xD;
&#xD;
          -  Active infection requiring systemic therapy.&#xD;
&#xD;
          -  Brain metastases or spinal cord compression. Patients with suspected brain metastases&#xD;
             at screening should have an MRI (preferred) or CT each preferably with IV contrast of&#xD;
             the brain prior to study entry. Patients whose brain metastases have been treated may&#xD;
             be considered if they have completed their treatment for brain metastasis at least 4&#xD;
             weeks prior to study registration provided they show radiographic stability (defined&#xD;
             as 1 brain image, obtained after treatment to the brain metastases). In addition, any&#xD;
             neurologic symptoms that developed either as a result of the brain metastases or their&#xD;
             treatment must have resolved or be stable without the use of steroids for at least 14&#xD;
             days prior to the start of treatment.&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  History of another primary malignancy except for:&#xD;
&#xD;
               -  Malignancy treated with curative intent and with no known active disease ≥5 years&#xD;
                  before the first dose of IP and of low potential risk for recurrence.&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease.&#xD;
&#xD;
               -  Adequately treated carcinoma in situ without evidence of disease.&#xD;
&#xD;
          -  Treatment with any investigational drug within 14 days prior to study registration.&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with&#xD;
             the exception of diverticulosis], celiac disease, irritable bowel disease, or other&#xD;
             serious gastrointestinal chronic conditions associated with diarrhea, systemic lupus&#xD;
             erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with&#xD;
             polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc])&#xD;
             within the last 3 years prior to study registration. The following are exceptions to&#xD;
             this criterion: The following are exceptions to this criterion:&#xD;
&#xD;
               -  Subjects with vitiligo or alopecia.&#xD;
&#xD;
               -  Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone&#xD;
                  replacement.&#xD;
&#xD;
               -  Any chronic skin condition that does not require systemic therapy.&#xD;
&#xD;
               -  Subjects without active disease in the last 5 years may be included but only&#xD;
                  after consultation with the study physician.&#xD;
&#xD;
               -  Subjects with celiac disease controlled by diet alone.&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or&#xD;
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of&#xD;
             prednisone, or an equivalent corticosteroid. The following are exceptions to this&#xD;
             criterion:&#xD;
&#xD;
               -  Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra&#xD;
                  articular injection).&#xD;
&#xD;
               -  Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of&#xD;
                  prednisone or its equivalent.&#xD;
&#xD;
               -  Steroids as premedication for hypersensitivity reactions (eg, CT scan&#xD;
                  premedication).&#xD;
&#xD;
          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca/&#xD;
             MedImmune staff and/or staff at the study site).&#xD;
&#xD;
          -  Concurrent enrollment in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study or during the follow-up period of an&#xD;
             interventional study.&#xD;
&#xD;
          -  Any concurrent chemotherapy, biologic or hormonal therapy for cancer treatment.&#xD;
             Concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone&#xD;
             replacement therapy) is acceptable. Note: Local treatment of isolated lesions,&#xD;
             excluding target lesions, for palliative intent is acceptable (e.g., local surgery or&#xD;
             radiotherapy).&#xD;
&#xD;
          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to&#xD;
             study registration. Note: local surgery of isolated lesions for palliative intent is&#xD;
             acceptable.&#xD;
&#xD;
          -  History of allogenic organ transplantation that requires use of immunosuppressive&#xD;
             agents.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirement,&#xD;
             substantially increase risk of incurring AEs or compromise the ability of the patient&#xD;
             to give written informed consent.&#xD;
&#xD;
          -  History of leptomeningeal carcinomatosis.&#xD;
&#xD;
          -  Active infection including tuberculosis (clinical evaluation that includes clinical&#xD;
             history, physical examination and radiographic findings), hepatitis B (known positive&#xD;
             HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus&#xD;
             (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined&#xD;
             as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are&#xD;
             eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if&#xD;
             polymerase chain reaction is negative for HCV RNA.&#xD;
&#xD;
          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of study&#xD;
             drug. Note: patients, if enrolled, should not receive live vaccine during the study&#xD;
             and up to 30 days after the last dose of study drug.&#xD;
&#xD;
          -  Female patients who are pregnant or breastfeeding or male or female patients of&#xD;
             reproductive potential who are not willing to employ effective birth control from&#xD;
             screening to 90 days after the last dose of study drug.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to study drugs or other humanized monoclonal&#xD;
             antibodies.&#xD;
&#xD;
          -  Patient ≤30kg in weight.&#xD;
&#xD;
          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3&#xD;
             electrocardiograms (ECGs) using Fridericia's Correction.&#xD;
&#xD;
          -  Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the&#xD;
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion&#xD;
             criteria:&#xD;
&#xD;
               -  Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after&#xD;
                  consultation with the Study Physician.&#xD;
&#xD;
               -  Subjects with irreversible toxicity not reasonably expected to be exacerbated by&#xD;
                  treatment with durvalumab may be included only after consultation with the Study&#xD;
                  Physician.&#xD;
&#xD;
          -  Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required&#xD;
             steroid treatment, or any evidence of clinically active interstitial lung disease.&#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>Ajjai Alva, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Univerisity of Illinois Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hosptials and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Cancer Institute</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.bigtencrc.org</url>
    <description>Big Ten Cancer Research Consortium Website</description>
  </link>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>October 9, 2017</study_first_submitted>
  <study_first_submitted_qc>October 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <last_update_submitted>February 16, 2022</last_update_submitted>
  <last_update_submitted_qc>February 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Big Ten Cancer Research Consortium</investigator_affiliation>
    <investigator_full_name>Ajjai Alva, MD</investigator_full_name>
    <investigator_title>Sponsor-Investigator</investigator_title>
  </responsible_party>
  <keyword>Durvalumab</keyword>
  <keyword>Guadecitabine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
    <mesh_term>Kidney Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Guadecitabine</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>August 3, 2022</submitted>
    <returned>August 26, 2022</returned>
  </pending_results>
  <!-- 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/NCT03308396
org study id: BTCRC-GU16-043
nct id: NCT03308396
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a single arm, multi-centre (via Big Ten Cancer Research Consortium) phase Ib/II study
      of patients treated with durvalumab 1500 mg IV q 4 weeks in combination with guadecitabine at
      the recommended phase 2 dose subcutaneously for 5 consecutive days. Eligible patients will
      have metastatic RCC with a clear cell component, ECOG performance status of 0-1, have
      received 0-1 prior therapy but no prior anti-PD-1/PD-L1/CTLA4 (Cohort 1, 36 subjects). Study
      treatment could potentially continue for up to 13 cycles (52 weeks).
A total of up to 58 subjects will be enrolled on both phases.

      Phase Ib: 6-12 subjects; enrolled into either Cohort 1 or 2. Phase II: 46 subjects; enrolled
      into either Cohort 1 or 2.

      Cohort 1 (36 subjects): received 0-1 prior therapy and no prior anti-PD-1/PD-L1/CTLA4.

      Cohort 2 (16 subjects): received up to 2 prior therapies, one of which must include an
      anti-PD-1/PD-L1 therapy to which they did not respond. Only one prior anti-PD-1/PD-L1 therapy
      is allowed.

      Patients from Phase Ib treated at the eventual phase II dose will be combined with patients
      in Phase II in the efficacy analysis.

        -  Therapy will start with guadecitabine on days 1-5 of a 28-day cycle. Guadecitabine will
           be dosed subcutaneously on days 1-5 at either dose level 0 (60 mg/m2) or dose level -1
           (45 mg/m2), based on the recommended phase II dose.

        -  Durvalumab will be started on day 8 of the 28-day cycle. Durvalumab will be administered
           intravenously at a flat dose of 1500mg every 28 days.

        -  Study treatment may continue for up to 13 cycles (52 weeks) in the absence of confirmed
           progression, intolerable toxicity, or withdrawal of consent.

      Phase Ib Treatment Plan

        -  Dose limiting toxicities (DLTs) will be evaluated within the first cycle (i.e., within
           the first 28 days).

        -  Six patients will be enrolled at dose level 0. If 2 or fewer patients experience a dose
           limiting toxicity, the study will continue to the phase II portion at dose level 0.

        -  Alternately, if 3 or more patients have a dose limiting toxicity at dose level 0, 6
           patients will be accrued at the lower dose (dose -1). If 2 or fewer patients experience
           a dose limiting toxicity, the study will continue to phase II at dose level -1.

        -  If 3 or more subjects experience a dose limiting toxicity at dose level -1, the
           treatment will be considered unsafe and the trial will be stopped. In this case,
           durvalumab and guadecitabine will be permanently discontinued and the subjects followed
           per protocol.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Phase Ib/II
primary purpose: Treatment
masking: None (Open Label)
masking description: Open-label
measure: Phase Ib: Dose limiting toxicities will be assessed to determine if the trial is stopped before the Phase II portion.
time frame: 28 days/First cycle
description: Number of patients with dose-limiting toxicity (DLT) of the combination of durvalumab and guadecitabine
measure: Objective response rate
time frame: 1 year
description: Objective response rate (complete response (CR) + partial response (PR)) by RECIST 1.1 in Cohort 1
measure: Phase II: Overall Survival (OS)
time frame: 2 years
description: will be reported with 95% confidence intervals from the Kaplan-Meier estimates.
measure: Phase II: Duration of Response (DoR)
time frame: 2 years
description: will be assessed using Kaplan-Meier estimates including the 95% confidence band separately for cohort 1 and for cohort 2.
measure: Phase II: Progression-free survival (PFS)
time frame: 2 years
description: will be assessed using Kaplan-Meier estimates including the 95% confidence band separately for cohort 1 and for cohort 2.
measure: Phase II: Clinical benefit rate (CBR)
time frame: 2 years
description: reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2
measure: Phase II: Complete response (CR) proportion
time frame: 2 years
description: reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2
measure: Phase II: Objective Response Rate (ORR)
time frame: 2 years
description: reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2
measure: Phase II: Assess Adverse Events
time frame: 2 years
description: by CTCAE ver 4 including events of special interest such as immune mediated toxicities
arm group label: Single Arm
arm group type: Experimental
description: This is a non-randomized, single arm, open label Phase Ib/II study.
Phase Ib:
Days 1-5
Guadecitabine:
Dose 0: 60 mg/m^2
Dose -1: 45 mg/m^2
Phase II:
Days 1-5 Guadecitabine (at Ph II dose)
Day 8 Durvalumab (1500 mg IV) Day 8 Durvalumab (1500 mg IV)
intervention type: Drug
intervention name: Guadecitabine
description: Days 1-5 Dose 0: 60 mg/m^2 Dose -1: 45 mg/m^2
arm group label: Single Arm
other name: SGI-110
intervention type: Drug
intervention name: Durvalumab
description: Day 8 Durvalumab (1500 mg IV)
arm group label: Single Arm
other name: MEDI4736
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ajjai Alva, M.D.
role: Principal Investigator
affiliation: University of Michigan
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.bigtencrc.org
description: Big Ten Cancer Research Consortium Website
responsible party type: Sponsor-Investigator
investigator affiliation: Big Ten Cancer Research Consortium
investigator full name: Ajjai Alva, MD
investigator title: Sponsor-Investigator
mesh term: Carcinoma, Renal Cell
mesh term: Kidney Neoplasms
mesh term: Durvalumab
mesh term: Guadecitabine
submitted: August 3, 2022
returned: August 26, 2022