<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/NCT04477512</url>
  </required_header>
  <id_info>
    <org_study_id>202009082</org_study_id>
    <nct_id>NCT04477512</nct_id>
  </id_info>
  <brief_title>Cabozantinib and Abiraterone With Checkpoint Inhibitor Immunotherapy in Metastatic Hormone Sensitive Prostate Cancer (CABIOS Trial)</brief_title>
  <official_title>A Phase 1b Clinical Trial of Cabozantinib and Abiraterone With Checkpoint Inhibitor Immunotherapy in Metastatic Hormone Sensitive Prostate Cancer (CABIOS Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Exelixis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to determine the recommended phase 2 dose of the multi-drug&#xD;
      combination of abiraterone, cabozantinib, and nivolumab in conjunction with ongoing androgen&#xD;
      deprivation therapy in previously untreated metastatic hormone-sensitive prostate cancer&#xD;
      patients. The investigators hypothesize that the combination of cabozantinib and abiraterone&#xD;
      acetate/prednisone in conjunction with nivolumab will have an acceptable safety profile and&#xD;
      will be feasible to administer in patients with hormone-sensitive metastatic prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 19, 2021</start_date>
  <completion_date type="Anticipated">March 31, 2026</completion_date>
  <primary_completion_date type="Actual">September 9, 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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of dose-limiting toxicities (DLTs)</measure>
    <time_frame>Completion of 1st cycle of treatment for patients in dose level 1 &amp; dose level 2 (estimated to be 11 months)</time_frame>
    <description>Protocol defined hematologic DLTs that occur during the first cycle that are attributed as possibly, probably, or definitely related to study treatment&#xD;
Protocol defined non-hematologic DLTs possibly, probably, or definitely related grade 3 or 4 non-hematologic toxicity that occurs during the first cycle of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PSA response rate</measure>
    <time_frame>Through end of treatment (estimated to be 24 months)</time_frame>
    <description>-PSA response rate will be defined as the proportion of subjects who have PSA response as defined by at least 50% decline in PSA level from baseline measured twice at least 3 weeks apart. Based on the PCWG3 criteria, a favorable effect on PSA may be delayed for ≥ 12 weeks. Therefore, early rises in PSA before 12 weeks will not be considered when determining PSA response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>Through end of treatment (estimated to be 24 months)</time_frame>
    <description>-The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From start of treatment through 1 year of follow-up (estimated to be 36 months)</time_frame>
    <description>-Defined as time of enrollment to time of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>From start of treatment through 1 year of follow-up (estimated to be 36 months)</time_frame>
    <description>Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of first PCWG3 defined progression or death, the event that occurs first. Patients who have not experienced either event at the time of analysis will be censored at the date of their last progression assessment.&#xD;
For rising PSA after an initial decline from baseline, the PSA is recorded from the start of therapy to first PSA increase that is ≥ 25% and ≥ 2ng/mL above the nadir, which is confirmed by a second value 4 or more weeks later, confirming a rising trend. If there is no initial decline from baseline, PSA progression is defined as ≥ 25% increase and ≥ 2 ng/mL increase from baseline beyond 12 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease specific survival (DSS)</measure>
    <time_frame>From start of treatment through 1 year of follow-up (estimated to be 36 months)</time_frame>
    <description>-Defined as time of enrollment to time of prostate-cancer related death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events as measured per CTCAE v 5.0</measure>
    <time_frame>From time of consent through 100 days after last dose of nivolumab (estimated to be 28 months)</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Metastatic Hormone Refractory Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Level 1: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be 20 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Level 2: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be 40 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expansion: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be dependent on recommended dose found in first part of study</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabozantinib</intervention_name>
    <description>Supplied by Exelixis</description>
    <arm_group_label>Expansion: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 1: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 2: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Supplied by Bristol-Myers Squibb</description>
    <arm_group_label>Expansion: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 1: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 2: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abiraterone acetate</intervention_name>
    <description>Commercially available</description>
    <arm_group_label>Expansion: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 1: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 2: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Commercially available</description>
    <arm_group_label>Expansion: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 1: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 2: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral blood collection</intervention_name>
    <description>Prior to start of treatment, after 8 weeks of combination therapy, with every subsequent imaging (every 12 weeks), end of treatment</description>
    <arm_group_label>Expansion: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 1: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
    <arm_group_label>Level 2: Cabozantinib+Abiraterone acetate +Nivolumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed hormone-sensitive prostate adenocarcinoma.&#xD;
&#xD;
          -  Must have evidence of metastatic disease on CT or MRI of the chest, abdomen, and&#xD;
             pelvis, or technetium bone scan. May have any type or location of metastases (bone,&#xD;
             lymph node, visceral). May have relapsed metastatic disease after initial primary&#xD;
             therapy or de novo metastatic disease. Metastatic disease does not have to be&#xD;
             confirmed by biopsy.&#xD;
&#xD;
          -  May have been on androgen deprivation therapy (ADT) for metastatic hormone-sensitive&#xD;
             prostate cancer for ≤ 12 weeks prior to study enrollment (GnRHR agonist such as&#xD;
             leuprolide, goserelin, triptorelin, buserelin, histrelin; GnRHR antagonists such as&#xD;
             degarelix, or relugolix). Prior ADT for localized prostate cancer is allowed.&#xD;
&#xD;
          -  Prior palliative radiation therapy for bone metastasis (must be complete ≥14 days&#xD;
             prior to enrollment) or any other radiation therapy (must be complete ≥28 days prior&#xD;
             to enrollment) is allowed. Prior definitive radiation therapy for localized prostate&#xD;
             cancer is allowed.&#xD;
&#xD;
          -  If the patient has undergone bilateral orchiectomy, it must have occurred no more than&#xD;
             12 weeks before study enrollment.&#xD;
&#xD;
          -  Recovery to baseline or ≤ grade 1 from toxicities related to any prior treatments,&#xD;
             unless AEs are clinically nonsignificant and/or stable on supportive therapy.&#xD;
&#xD;
          -  At least 18 years of age.&#xD;
&#xD;
          -  ECOG performance status ≤ 1&#xD;
&#xD;
          -  Normal bone marrow and organ function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1,500 K/cumm without granulocyte colony-stimulating&#xD;
                  factor support&#xD;
&#xD;
               -  White blood cell count ≥ 2,500 K/cumm&#xD;
&#xD;
               -  Platelets ≥ 100,000 K/cumm without transfusion&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/DL&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3.0 x IULN)&#xD;
&#xD;
               -  AST(SGOT), ALT(SGPT), and alkaline phosphatase (ALP) ≤ 3.0 x IULN; ALP ≤ 5.0 x&#xD;
                  IULN with documented bone metastases&#xD;
&#xD;
               -  Serum creatinine ≤ 2.0 x IULN or calculated creatinine clearance ≥ 30 mL/min by&#xD;
                  Cockcroft-Gault&#xD;
&#xD;
               -  Serum albumin ≥ 2.8 g/dL&#xD;
&#xD;
               -  Urine protein/creatinine ration (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol)), or 24h urine&#xD;
                  protein ≤1g&#xD;
&#xD;
               -  PT/INR or PTT &lt; 1.3 x IULN&#xD;
&#xD;
          -  Castrate testosterone levels with serum testosterone ≤ 50 ng/mL at time of study drug&#xD;
             start, with ongoing ADT throughout the study unless prior bilateral orchiectomy.&#xD;
&#xD;
          -  Corrected QT interval calculated by the Fridericia formula (QTcF) ≤ 500 ms (by ECG)&#xD;
&#xD;
          -  Ability to understand and willingness to sign an IRB approved written informed consent&#xD;
             document (or that of the legally authorized representative, if applicable).&#xD;
&#xD;
          -  Sexually active fertile subjects and their partners must agree to use medically&#xD;
             accepted methods of contraception (e.g., barrier methods, including male condom,&#xD;
             female condom, or diaphragm with spermicidal gel) during the course of the study and&#xD;
             for 4 months after the last dose of study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any evidence of neuroendocrine/small cell prostate cancer, or castrate resistant&#xD;
             prostate cancer, as defined by defined by disease progression despite androgen&#xD;
             depletion therapy (ADT), either by continuous rise in serum PSA levels as measured&#xD;
             over at least 2 consecutive values, or the clinical or radiographic progression of&#xD;
             disease, as assessed by the investigator.&#xD;
&#xD;
          -  Prior exposure to second-generation androgen receptor inhibitors (e.g., enzalutamide,&#xD;
             apalutamide, darolutamide).&#xD;
&#xD;
          -  Prior exposure to CYP17 inhibitors (e.g. abiraterone)&#xD;
&#xD;
          -  No chronic concomitant treatment with strong cytochrome P450 (CYP) 3A4 inducers or&#xD;
             inhibitors. If patients are on such agents and these can be safely discontinued, may&#xD;
             not have received a strong CYP3A4 inducer/inhibitor within 5 half-lives.&#xD;
&#xD;
          -  Prior systemic chemotherapy for prostate cancer (either for localized or metastatic&#xD;
             disease). Patients may have received androgen deprivation therapy (ADT) for &lt; 12 weeks&#xD;
             prior to start of study drug; no other cytotoxic, biologic, or other systemic&#xD;
             anticancer therapy (including investigational) within 4 weeks before first dose of&#xD;
             study treatment.&#xD;
&#xD;
          -  Prior treatment with checkpoint inhibitor or other immunotherapy (e.g., anti-PD-1,&#xD;
             anti-PD-L1, anti-CTLA4).&#xD;
&#xD;
          -  Prior treatment with cabozantinib.&#xD;
&#xD;
          -  Receipt of any type of small molecule kinase inhibitor (including investigational&#xD;
             kinase inhibitor) within 2 weeks before first dose of study treatment.&#xD;
&#xD;
          -  Inability to swallow pills.&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g., colitis or Crohns 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;
          -  Presence of a condition requiring systemic treatment with either corticosteroids (&gt; 10&#xD;
             mg daily prednisone equivalent) or other immunosuppressive medications within 14&#xD;
             calendar days of start of study treatment. Inhaled or topical steroids and adrenal&#xD;
             replacement steroid doses &lt; 10 mg daily prednisone equivalent are permitted in the&#xD;
             absence of active autoimmune disease.&#xD;
&#xD;
          -  Any other active malignancy at time of first dose of study treatment or diagnosis of&#xD;
             another malignancy within 3 years prior to first dose of study treatment that requires&#xD;
             active treatment, except for locally curable cancers that have been apparently cured,&#xD;
             such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma&#xD;
             in situ of the prostate, cervix, or breast.&#xD;
&#xD;
          -  Currently receiving any other investigational agents.&#xD;
&#xD;
          -  Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin&#xD;
             inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet&#xD;
             inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:&#xD;
&#xD;
               -  Prophylactic use of low-dose aspirin for cardioprotection (per applicable local&#xD;
                  guidelines) and low-dose low molecular weight heparins (LMWH)&#xD;
&#xD;
               -  Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors&#xD;
                  rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who&#xD;
                  are on a stable dose of the anticoagulant for at least one week before the first&#xD;
                  dose of study treatment without clinically significant hemorrhagic complications&#xD;
                  from the anticoagulation regimen or the tumor.&#xD;
&#xD;
          -  Patients with known brain metastases or cranial epidural disease unless adequately&#xD;
             treated with radiotherapy and/or surgery (including radiosurgery) and stable for at&#xD;
             least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4&#xD;
             weeks prior to first dose of study treatment after major surgery (e.g., removal or&#xD;
             biopsy of brain metastasis). Subjects must have complete wound healing from major&#xD;
             surgery or minor surgery before first dose of study treatment. Eligible subjects must&#xD;
             be neurologically asymptomatic and without corticosteroid treatment at the time of&#xD;
             first dose of study treatment.&#xD;
&#xD;
          -  A history of allergic reactions attributed to compounds of similar chemical or&#xD;
             biologic composition to cabozantinib, nivolumab, or abiraterone or other agents used&#xD;
             in the study.&#xD;
&#xD;
          -  Uncontrolled, significant intercurrent illness including, but not limited to, the&#xD;
             following conditions:&#xD;
&#xD;
               -  Cardiovascular disorders:&#xD;
&#xD;
                    -  Congestive heart failure New York Heart Association Class 3 or 4, unstable&#xD;
                       angina pectoris, serious cardiac arrhythmias.&#xD;
&#xD;
                    -  Uncontrolled hypertension defined as sustained blood pressure (BP) &gt; 140 mm&#xD;
                       Hg systolic or &gt; 90 mm Hg diastolic despite optimal antihypertensive&#xD;
                       treatment.&#xD;
&#xD;
                    -  Stroke (including transient ischemic attack [TIA]), myocardial infarction&#xD;
                       (MI), or other ischemic events, or thromboembolic event (e.g., deep venous&#xD;
                       thrombosis, pulmonary embolism) within six months before the first dose of&#xD;
                       study treatment.&#xD;
&#xD;
                         -  Subjects with a diagnosis of incidental, subsegmental PE or DVT within&#xD;
                            six months are allowed if stable, asymptomatic, and treated with&#xD;
                            anticoagulation for at least 1 week before the first dose of study&#xD;
                            treatment.&#xD;
&#xD;
               -  Gastrointestinal (GI) disorders, including those associated with a high risk of&#xD;
                  perforation or fistula formation:&#xD;
&#xD;
                    -  The subject has evidence of tumor invading the GI tract, active peptic ulcer&#xD;
                       disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis,&#xD;
                       cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis,&#xD;
                       acute obstruction of the pancreatic duct or common bile duct, or gastric&#xD;
                       outlet obstruction.&#xD;
&#xD;
                    -  Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal&#xD;
                       abscess within six months before the first dose.&#xD;
&#xD;
        Note: Complete healing of an intra-abdominal abscess must be confirmed before the first&#xD;
        dose.&#xD;
&#xD;
          -  Clinically significant hematuria, hematemesis, or hemoptysis of &gt; 0.5 teaspoon (2.5&#xD;
             ml) of red blood, or other history of significant bleeding (e.g., pulmonary&#xD;
             hemorrhage) within 12 weeks before the first dose.&#xD;
&#xD;
          -  Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease&#xD;
             manifestation.&#xD;
&#xD;
          -  Lesions invading or encasing any major blood vessels.&#xD;
&#xD;
          -  Other clinically significant disorders that would preclude safe study participation.&#xD;
&#xD;
               -  Serious non-healing wound/ulcer/bone fracture.&#xD;
&#xD;
               -  Uncompensated/symptomatic hypothyroidism.&#xD;
&#xD;
               -  Moderate to severe hepatic impairment (Child-Pugh B or C).&#xD;
&#xD;
                    -  Active hepatitis B or C; active HIV. Patients with well-controlled HIV or&#xD;
                       hepatitis B or C, or who have had curative treatment for hepatitis C, may be&#xD;
                       considered if they meet all other criteria and after discussion with the PI&#xD;
                       and drug manufacturers (BMS and Exelixis) using the following criteria for&#xD;
                       guidance: https://www.fda.gov/media/121319/download&#xD;
&#xD;
                    -  History of organ allograft.&#xD;
&#xD;
                    -  Major surgery (e.g., laparoscopic nephrectomy, GI surgery removal or biopsy&#xD;
                       of brain metastasis) within 2 weeks before the first dose of study&#xD;
                       treatment. Minor surgeries within 10 days before dose of study treatment&#xD;
                       (with the exception of the baseline biopsy, which must have occurred no less&#xD;
                       than 6 days prior to the first dose). Subjects must have complete wound&#xD;
                       healing from major surgery or minor surgery before first dose of study&#xD;
                       treatment. Patients with clinically relevant ongoing complications from&#xD;
                       prior surgery are not eligible.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Russell K Pachynski, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>March 31, 2023</last_update_submitted>
  <last_update_submitted_qc>March 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 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>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Abiraterone Acetate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04477512
org study id: 202009082
nct id: NCT04477512
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The goal of this study is to determine the recommended phase 2 dose of the multi-drug
      combination of abiraterone, cabozantinib, and nivolumab in conjunction with ongoing androgen
      deprivation therapy in previously untreated metastatic hormone-sensitive prostate cancer
      patients. The investigators hypothesize that the combination of cabozantinib and abiraterone
      acetate/prednisone in conjunction with nivolumab will have an acceptable safety profile and
      will be feasible to administer in patients with hormone-sensitive metastatic prostate cancer.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency of dose-limiting toxicities (DLTs)
time frame: Completion of 1st cycle of treatment for patients in dose level 1 & dose level 2 (estimated to be 11 months)
description: Protocol defined hematologic DLTs that occur during the first cycle that are attributed as possibly, probably, or definitely related to study treatment
Protocol defined non-hematologic DLTs possibly, probably, or definitely related grade 3 or 4 non-hematologic toxicity that occurs during the first cycle of treatment.
measure: PSA response rate
time frame: Through end of treatment (estimated to be 24 months)
description: -PSA response rate will be defined as the proportion of subjects who have PSA response as defined by at least 50% decline in PSA level from baseline measured twice at least 3 weeks apart. Based on the PCWG3 criteria, a favorable effect on PSA may be delayed for ≥ 12 weeks. Therefore, early rises in PSA before 12 weeks will not be considered when determining PSA response.
measure: Overall response rate (ORR)
time frame: Through end of treatment (estimated to be 24 months)
description: -The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
measure: Overall survival (OS)
time frame: From start of treatment through 1 year of follow-up (estimated to be 36 months)
description: -Defined as time of enrollment to time of death from any cause
measure: Progression-free survival (PFS)
time frame: From start of treatment through 1 year of follow-up (estimated to be 36 months)
description: Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of first PCWG3 defined progression or death, the event that occurs first. Patients who have not experienced either event at the time of analysis will be censored at the date of their last progression assessment.
For rising PSA after an initial decline from baseline, the PSA is recorded from the start of therapy to first PSA increase that is ≥ 25% and ≥ 2ng/mL above the nadir, which is confirmed by a second value 4 or more weeks later, confirming a rising trend. If there is no initial decline from baseline, PSA progression is defined as ≥ 25% increase and ≥ 2 ng/mL increase from baseline beyond 12 weeks.
measure: Disease specific survival (DSS)
time frame: From start of treatment through 1 year of follow-up (estimated to be 36 months)
description: -Defined as time of enrollment to time of prostate-cancer related death
measure: Incidence of adverse events as measured per CTCAE v 5.0
time frame: From time of consent through 100 days after last dose of nivolumab (estimated to be 28 months)
arm group label: Level 1: Cabozantinib+Abiraterone acetate +Nivolumab
arm group type: Experimental
description: -Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be 20 mg.
arm group label: Level 2: Cabozantinib+Abiraterone acetate +Nivolumab
arm group type: Experimental
description: -Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be 40 mg.
arm group label: Expansion: Cabozantinib+Abiraterone acetate +Nivolumab
arm group type: Experimental
description: -Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be dependent on recommended dose found in first part of study
intervention type: Drug
intervention name: Cabozantinib
description: Supplied by Exelixis
arm group label: Expansion: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 1: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 2: Cabozantinib+Abiraterone acetate +Nivolumab
intervention type: Drug
intervention name: Nivolumab
description: Supplied by Bristol-Myers Squibb
arm group label: Expansion: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 1: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 2: Cabozantinib+Abiraterone acetate +Nivolumab
intervention type: Drug
intervention name: Abiraterone acetate
description: Commercially available
arm group label: Expansion: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 1: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 2: Cabozantinib+Abiraterone acetate +Nivolumab
intervention type: Drug
intervention name: Prednisone
description: Commercially available
arm group label: Expansion: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 1: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 2: Cabozantinib+Abiraterone acetate +Nivolumab
intervention type: Procedure
intervention name: Peripheral blood collection
description: Prior to start of treatment, after 8 weeks of combination therapy, with every subsequent imaging (every 12 weeks), end of treatment
arm group label: Expansion: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 1: Cabozantinib+Abiraterone acetate +Nivolumab
arm group label: Level 2: Cabozantinib+Abiraterone acetate +Nivolumab
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Russell K Pachynski, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Nivolumab
mesh term: Abiraterone Acetate
sharing ipd: No