<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/NCT03773666</url>
  </required_header>
  <id_info>
    <org_study_id>18-507</org_study_id>
    <nct_id>NCT03773666</nct_id>
  </id_info>
  <brief_title>A Feasibility Study of Durvalumab +/- Oleclumab as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)</brief_title>
  <official_title>A Feasibility Study of Durvalumab (MEDI4736) Alone or in Combination With Oleclumab (MEDI9447) as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</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>
      This research study is studying a new anti-cancer drug durvalumab (MEDI4736) with or without&#xD;
      another new anti-cancer drug Oleclumab (MEDI9447) before surgery for bladder cancer.&#xD;
&#xD;
      The drugs involved in this study are:&#xD;
&#xD;
        -  Durvalumab (MEDI4736)&#xD;
&#xD;
        -  Oleclumab (MEDI9447)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Feasibility Study, which is the first time investigators are&#xD;
      examining these drugs, Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in patients with&#xD;
      muscle-invasive bladder cancer (MIBC) cancer prior to surgery. Cisplatin-containing&#xD;
      chemotherapy given before surgery is the standard of care in patients with MIBC because it&#xD;
      increases the rate of cure after surgery. Participants may still be eligible for this study&#xD;
      if their doctor determines that participants are able to receive cisplatin-containing&#xD;
      chemotherapy, but the participants elect not to undergo chemotherapy before surgery,&#xD;
      understanding the potential benefits of chemotherapy. The FDA (the U.S. Food and Drug&#xD;
      Administration) has not approved Durvalumab (MEDI4736) for localized bladder cancer prior to&#xD;
      surgery, but it has been approved for other uses, including for locally advanced or&#xD;
      metastatic bladder cancer after progression on platinum-containing chemotherapy. The FDA (the&#xD;
      U.S. Food and Drug Administration) has not approved Oleclumab (MEDI9447) as a treatment for&#xD;
      any disease. Durvalumab is a monoclonal antibody (an antibody is a protein produced by the&#xD;
      body's immune system) that works by blocking the Programmed Cell Death Ligand 1 (PD-L1), a&#xD;
      protein on cancer cells that stops the body's immune system from killing cancer cells, to&#xD;
      increase the body's immune response to prevent or slow down cancer growth. Oleclumab is a&#xD;
      monoclonal antibody that works by reducing the amount of adenosine, a small molecule called a&#xD;
      metabolite that binds to adenosine receptors on immune cells to regulate the immune system&#xD;
      and suppress the immune response. Reducing the amount of immunosuppressive adenosine can&#xD;
      increase the body's immune response to kill cancer cells. It is hoped that by combining&#xD;
      Oleclumab with Durvalumab, an even greater immune response against the tumor will be&#xD;
      generated. This research study is designed to see if the new anti-cancer drug Durvalumab&#xD;
      (MEDI4736) with or without another new anti-cancer drug Oleclumab (MEDI9447) can be safely&#xD;
      administered before surgery for bladder cancer&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 20, 2019</start_date>
  <completion_date type="Actual">August 2, 2021</completion_date>
  <primary_completion_date type="Actual">February 4, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Receiving at least One Dose of Study Therapy Followed by Surgery without Dose-Limiting Toxicity (DLT) up to Twelve Weeks Post-Radical Cystectomy (RC)</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Receiving at least One Cycle of Study Therapy and Undergone RC Having &lt;pT2N0 Disease at Time of RC</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Time of RC to Time of Documented Disease Relapse or Recurrence after RC</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic Progression by RECIST 1.1 Criteria from Time of Baseline Screening Imaging to the End of Treatment Imaging Pre-RC</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Muscle Invasive Bladder Cancer</condition>
  <arm_group>
    <arm_group_label>Durvalumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>-Durvalumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Durvalumab + Oleclumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle&#xD;
Oleclumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab is a monoclonal antibody (an antibody is a protein produced by the body's immune system) that works by blocking the Programmed Cell Death Ligand 1 (PD-L1), a protein on cancer cells that stops the body's immune system from killing cancer cells.</description>
    <arm_group_label>Durvalumab</arm_group_label>
    <arm_group_label>Durvalumab + Oleclumab</arm_group_label>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oleclumab</intervention_name>
    <description>Oleclumab is a monoclonal antibody that works by reducing the amount of adenosine, a small molecule called a metabolite that binds to adenosine receptors on immune cells to regulate the immune system and suppress the immune response. Reducing the amount of immunosuppressive adenosine can increase the body's immune response to kill cancer cells.</description>
    <arm_group_label>Durvalumab + Oleclumab</arm_group_label>
    <other_name>MEDI9447</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For inclusion in the study patients must fulfil all of the following criteria: Written&#xD;
             informed consent and any locally-required authorization (e.g. HIPAA) obtained from the&#xD;
             patient prior to performing any protocol-related procedures, including screening&#xD;
             evaluations&#xD;
&#xD;
          -  Age &gt; 18 years at time of study entry&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix&#xD;
             A).&#xD;
&#xD;
          -  Histologically confirmed bladder transitional cell carcinoma (TCC)&#xD;
&#xD;
             ---Patients with mixed histology are required to have a component of TCC, and no&#xD;
             component of small cell histology&#xD;
&#xD;
          -  T2-T4a N0 M0 disease, considered appropriate and planned for radical cystectomy&#xD;
&#xD;
          -  Ineligible for cisplatin-based chemotherapy, defined by any of the following:&#xD;
&#xD;
               -  Creatinine clearance (CL) &lt;60 mL/min. GFR should be calculated from serum/plasma&#xD;
                  creatinine using the Cockcroft-gault formula.&#xD;
&#xD;
               -  CTCAE v5.0 Grade &gt; 1 hearing loss&#xD;
&#xD;
               -  CTCAE v5.0 Grade &gt; 1 neuropathy&#xD;
&#xD;
               -  NYHA Class &gt; II cardiac dysfunction&#xD;
&#xD;
          -  Patients not meeting the above criteria are eligible if she/he declines perioperative&#xD;
             cisplatin-based chemotherapy after specific informed consent describing the known&#xD;
             benefits of cisplatin-based chemotherapy.&#xD;
&#xD;
          -  Adequate organ function laboratory values as defined below:&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) 1.5 x (&gt; 1500 per mm3)&#xD;
&#xD;
               -  Platelet count ≥100 x 109/L (&gt;75,000 per mm3)&#xD;
&#xD;
               -  Albumin &gt; 2.5 g/dL&#xD;
&#xD;
               -  International Normalized Ratio (INR) or activated partial thromboplastin time&#xD;
                  (aPTT) &lt; 1.5 x ULN, unless the patient is receiving anticoagulation therapy&#xD;
                  provided INR or PTT is within the therapeutic range of the intended anticoagulant&#xD;
                  therapy.&#xD;
&#xD;
               -  Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)&#xD;
&#xD;
                  ---This will not apply to patients with confirmed Gilbert's syndrome (persistent&#xD;
                  or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence&#xD;
                  of hemolysis or hepatic pathology), who will be allowed only in consultation with&#xD;
                  their physician.&#xD;
&#xD;
               -  AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal&#xD;
&#xD;
               -  Measured creatinine CL &gt;30 mL/min or Calculated creatinine CL&gt;30 mL/min by the&#xD;
                  Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection&#xD;
                  for determination of creatinine clearance:&#xD;
&#xD;
                    -  Males:&#xD;
&#xD;
                    -  Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine&#xD;
                       (mg/dL)&#xD;
&#xD;
                    -  Females:&#xD;
&#xD;
                    -  Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum&#xD;
                       creatinine (mg/dL)&#xD;
&#xD;
          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients. Women will be considered post-menopausal if they have&#xD;
             been amenorrheic for 12 months without an alternative medical cause. The following&#xD;
             age-specific requirements apply:&#xD;
&#xD;
               -  Women &lt;50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone&#xD;
                  levels in the postmenopausal range for the institution or underwent surgical&#xD;
                  sterilization (bilateral oophorectomy or hysterectomy).&#xD;
&#xD;
               -  Women ≥50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal&#xD;
                  treatments, had radiationinduced menopause with last menses &gt;1 year ago, had&#xD;
                  chemotherapy-induced menopause with last menses &gt;1 year ago, or underwent&#xD;
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or&#xD;
                  hysterectomy).&#xD;
&#xD;
          -  Patient is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations including follow&#xD;
             up.&#xD;
&#xD;
          -  Availability of baseline archival tumor tissue obtained for correlative studies dated&#xD;
             within 8 weeks of study registration.&#xD;
&#xD;
               -  Either FFPE tumor tissue block or a minimum of fifteen 5μm unstained FFPE slides&#xD;
                  and fifteen 10μm unstained FFPE slides with an associated pathology report is&#xD;
                  required.&#xD;
&#xD;
               -  Patients without adequate baseline tumor tissue or have archival tumor tissue &gt;8&#xD;
                  weeks from registration must undergo cystoscopic tumor biopsy, meeting the above&#xD;
                  tissue criteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with primary TCC of the ureter, urethra, or renal pelvis without TCC of the&#xD;
             bladder&#xD;
&#xD;
          -  Inoperable tumor(s) with fixation to the pelvic wall on clinical exam&#xD;
&#xD;
          -  Any previous systemic chemotherapy or radiotherapy for TCC of bladder&#xD;
&#xD;
          -  Participation in another clinical study with an investigational product during the&#xD;
             last 6 months&#xD;
&#xD;
          -  Concurrent enrolment 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 previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab&#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 study drug 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 (e.g. cervical&#xD;
                  cancer in situ)&#xD;
&#xD;
          -  Receipt of the last dose of intravesical chemotherapy or biologic therapy&#xD;
&#xD;
             ≤ 42 days (6 weeks) prior to the first dose of study drug for patients who have&#xD;
             received prior intravesical chemotherapy or biologic therapy (e.g. BCG)&#xD;
&#xD;
          -  Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)&#xD;
&#xD;
             ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) for durvalumab +&#xD;
             oleclumab cohorts only. Patient safety and the cardiac EKG should be consulted as&#xD;
             needed.&#xD;
&#xD;
          -  Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer&#xD;
             therapy with the exception of alopecia, vitiligo, and the laboratory values defined in&#xD;
             the inclusion criteria&#xD;
&#xD;
               -  Patients with Grade ≥2 neuropathy will be evaluated on a case-bycase basis after&#xD;
                  consultation with the Study Physician.&#xD;
&#xD;
               -  Patients with irreversible toxicity not reasonably expected to be exacerbated by&#xD;
                  treatment with durvalumab and/or oleclumab may be included only after&#xD;
                  consultation with the Study Physician.&#xD;
&#xD;
          -  Any concurrent chemotherapy, IP, 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.&#xD;
&#xD;
          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of IP. Note: Local surgery of isolated lesions for palliative intent is&#xD;
             acceptable.&#xD;
&#xD;
          -  History of allogenic organ transplantation&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g. colitis or Crohn's disease], diverticulitis [with the&#xD;
             exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or&#xD;
             Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid&#xD;
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this&#xD;
             criterion:&#xD;
&#xD;
               -  Patients with vitiligo or alopecia&#xD;
&#xD;
               -  Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on&#xD;
                  hormone replacement&#xD;
&#xD;
               -  Any chronic skin condition that does not require systemic therapy&#xD;
&#xD;
               -  Patients without active disease in the last 5 years may be included but only&#xD;
                  after consultation with the study physician&#xD;
&#xD;
               -  Patients with celiac disease controlled by diet alone&#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, serious chronic&#xD;
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirement, substantially increase&#xD;
             risk of incurring AEs or compromise the ability of the patient to give written&#xD;
             informed consent&#xD;
&#xD;
          -  History of leptomeningeal carcinomatosis&#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.&#xD;
&#xD;
          -  History of active primary immunodeficiency&#xD;
&#xD;
          -  Active infection including tuberculosis (clinical evaluation that includes clinical&#xD;
             history, physical examination and radiographic findings, and TB testing in line with&#xD;
             local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),&#xD;
             hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients&#xD;
             with a past or resolved HBV infection (defined as the presence of hepatitis B core&#xD;
             antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for&#xD;
             hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative&#xD;
             for HCV RNA.&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 14 days before the first&#xD;
             dose of study drug. The following are exceptions to this criterion:&#xD;
&#xD;
               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g. 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 (e.g. CT scan&#xD;
                  premedication)&#xD;
&#xD;
          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:&#xD;
             Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to&#xD;
             30 days after the last dose of IP.&#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 180 days after the last dose of durvalumab&#xD;
&#xD;
             + oleclumab or 90 days after the last dose of durvalumab monotherapy, whichever is the&#xD;
             longer time period&#xD;
&#xD;
          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
             excipients&#xD;
&#xD;
          -  Prior randomization or treatment in a previous durvalumab and/or oleclumab clinical&#xD;
             study regardless of treatment arm assignment&#xD;
&#xD;
          -  Judgment by the investigator that the patient is unsuitable to participate in the&#xD;
             study and the patient is unlikely to comply with study procedures, restrictions and&#xD;
             requirements&#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>Xiao X Wei, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 8, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>September 8, 2022</last_update_submitted>
  <last_update_submitted_qc>September 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Xiao X. Wei</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Bladder Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor-Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
    <ipd_access_criteria>Requests may be directed to: [contact information for Sponsor-Investigator or designee].</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT03773666
org study id: 18-507
nct id: NCT03773666
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study is studying a new anti-cancer drug durvalumab (MEDI4736) with or without
      another new anti-cancer drug Oleclumab (MEDI9447) before surgery for bladder cancer.

      The drugs involved in this study are:

        -  Durvalumab (MEDI4736)

        -  Oleclumab (MEDI9447)
This research study is a Feasibility Study, which is the first time investigators are
      examining these drugs, Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in patients with
      muscle-invasive bladder cancer (MIBC) cancer prior to surgery. Cisplatin-containing
      chemotherapy given before surgery is the standard of care in patients with MIBC because it
      increases the rate of cure after surgery. Participants may still be eligible for this study
      if their doctor determines that participants are able to receive cisplatin-containing
      chemotherapy, but the participants elect not to undergo chemotherapy before surgery,
      understanding the potential benefits of chemotherapy. The FDA (the U.S. Food and Drug
      Administration) has not approved Durvalumab (MEDI4736) for localized bladder cancer prior to
      surgery, but it has been approved for other uses, including for locally advanced or
      metastatic bladder cancer after progression on platinum-containing chemotherapy. The FDA (the
      U.S. Food and Drug Administration) has not approved Oleclumab (MEDI9447) as a treatment for
      any disease. Durvalumab is a monoclonal antibody (an antibody is a protein produced by the
      body's immune system) that works by blocking the Programmed Cell Death Ligand 1 (PD-L1), a
      protein on cancer cells that stops the body's immune system from killing cancer cells, to
      increase the body's immune response to prevent or slow down cancer growth. Oleclumab is a
      monoclonal antibody that works by reducing the amount of adenosine, a small molecule called a
      metabolite that binds to adenosine receptors on immune cells to regulate the immune system
      and suppress the immune response. Reducing the amount of immunosuppressive adenosine can
      increase the body's immune response to kill cancer cells. It is hoped that by combining
      Oleclumab with Durvalumab, an even greater immune response against the tumor will be
      generated. This research study is designed to see if the new anti-cancer drug Durvalumab
      (MEDI4736) with or without another new anti-cancer drug Oleclumab (MEDI9447) can be safely
      administered before surgery for bladder cancer
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants Receiving at least One Dose of Study Therapy Followed by Surgery without Dose-Limiting Toxicity (DLT) up to Twelve Weeks Post-Radical Cystectomy (RC)
time frame: 2 years
measure: Number of Participants Receiving at least One Cycle of Study Therapy and Undergone RC Having <pT2N0 Disease at Time of RC
time frame: 2 years
measure: Duration of Time of RC to Time of Documented Disease Relapse or Recurrence after RC
time frame: 2 years
measure: Radiographic Progression by RECIST 1.1 Criteria from Time of Baseline Screening Imaging to the End of Treatment Imaging Pre-RC
time frame: 2 years
arm group label: Durvalumab
arm group type: Experimental
description: -Durvalumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle
arm group label: Durvalumab + Oleclumab
arm group type: Experimental
description: Durvalumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle
Oleclumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab is a monoclonal antibody (an antibody is a protein produced by the body's immune system) that works by blocking the Programmed Cell Death Ligand 1 (PD-L1), a protein on cancer cells that stops the body's immune system from killing cancer cells.
arm group label: Durvalumab
arm group label: Durvalumab + Oleclumab
other name: MEDI4736
intervention type: Drug
intervention name: Oleclumab
description: Oleclumab is a monoclonal antibody that works by reducing the amount of adenosine, a small molecule called a metabolite that binds to adenosine receptors on immune cells to regulate the immune system and suppress the immune response. Reducing the amount of immunosuppressive adenosine can increase the body's immune response to kill cancer cells.
arm group label: Durvalumab + Oleclumab
other name: MEDI9447
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Xiao X Wei, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Xiao X. Wei
investigator title: Principal Investigator
mesh term: Urinary Bladder Neoplasms
mesh term: Durvalumab
sharing ipd: Yes
ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor-Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication
ipd access criteria: Requests may be directed to: [contact information for Sponsor-Investigator or designee].