<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/NCT02986100</url>
  </required_header>
  <id_info>
    <org_study_id>CO-338-045</org_study_id>
    <secondary_id>2015-004394-32</secondary_id>
    <nct_id>NCT02986100</nct_id>
  </id_info>
  <brief_title>Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib</brief_title>
  <acronym>AME</acronym>
  <official_title>An Open-Label, Non-Randomized, Phase I Study to Assess the Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>pharmaand GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>pharmaand GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to characterize the mass balance, absorption, metabolism, and&#xD;
      elimination pathways of orally administered [14C] rucaparib followed by cycle by cycle&#xD;
      treatment with rucaparib continuing until disease progression or other reason for&#xD;
      discontinuation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1, open-label, non-randomized, mass balance study in patients with&#xD;
      histologically or cytologically confirmed advanced solid tumors. Approximately 6 patients&#xD;
      will be enrolled. The study will consist of 2 parts: a mass balance part (Part I) and a&#xD;
      rucaparib treatment part (Part II).&#xD;
&#xD;
      Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140&#xD;
      µCi) in the fasted state. Patients will be confined at the study site for the collection of&#xD;
      blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be&#xD;
      discharged sooner than Day 13, if the discharge criteria are met. If the cumulative recovery&#xD;
      of radioactivity exceeds 90% of the administered dose or if radioactivity in urine and feces&#xD;
      is &lt; 1% of the administered dose over a 24 hour period on two consecutive days, as determined&#xD;
      by quick counts.&#xD;
&#xD;
      In Part II, the treatment with rucaparib in 28-day cycles will continue until progression of&#xD;
      disease, unacceptable toxicity, or other reason for discontinuation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">September 2018</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled rucaparib (radioactivity in whole blood and plasma): tmax</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Time to peak concentration (tmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): Cmax</measure>
    <time_frame>Days 1-13</time_frame>
    <description>peak (maximum) concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): t1/2</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Elimination half-life (t1/2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): AUC</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Area under curve (AUC)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): CL/F</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Oral clearance (CL/F)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): V/F</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Apparent volume of distribution (V/F)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Excretion rate of 14C-labeled rucaparib(radioactivity in feces)</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Percent of dose excreted in feces</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Excretion rate of 14C-labeled rucaparib(radioactivity in urine)</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Percent of dose excreted in urine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of rucaparib (in urine): CLR</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Renal clearance (CLR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Excretion rate of 14C-labeled rucaparib(radioactivity in vomit, if applicable)</measure>
    <time_frame>Days 1-13</time_frame>
    <description>Percent of dose in vomit, if applicable</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolite identification of rucaparib in plasma, urine and feces</measure>
    <time_frame>Days 1-13</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative whole blood:plasma ratio calculated for Cmax</measure>
    <time_frame>Days 1-13</time_frame>
    <description>peak concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative whole blood:plasma ratio calculated for AUC0-tlast</measure>
    <time_frame>Day 1-13</time_frame>
    <description>AUC from time zero to the last time point with concentration above the lower limit of quantitation (AUC0-last)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative whole blood:plasma ratio calculated for AUCinf</measure>
    <time_frame>Day 1-13</time_frame>
    <description>AUC from time zero to infinity (AUCinf)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tolerability and safety of rucaparib assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications</measure>
    <time_frame>From cycle 1 Day 1 until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks</time_frame>
    <description>Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications</description>
  </secondary_outcome>
  <other_outcome>
    <measure>To evaluate the antitumor activity of rucaparib in BRCA mutated solid tumors based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</measure>
    <time_frame>Cycle 1 Day 1 until progression of disease, unacceptable toxicity, or discontinuation for other reasons</time_frame>
    <description>Response will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and tumor markers per applicable criteria for a given tumor type</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>C-14 labeled rucaparib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met.&#xD;
After completion of Part I, patients with a deleterious BRCA mutation will have the option to participate in Part II by receiving 600 mg BID rucaparib tablets orally in 28 day cycles until disease progression, unacceptable toxicity, death, or discontinuation for other reasons</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>C-14 labeled Rucaparib</intervention_name>
    <description>Each dosage unit consists of a hard gelatin capsule filled with cold rucaparib camsylate and [14C]-rucaparib camsylate salt. Each capsule contains approximately 150 mg rucaparib (free base weight) and approximately 35 µCi of [14C]-rucaparib. Each patient will ingest four capsules in the fasted state for a total dose of 600 mg rucaparib (free base weight) with approximately 140 µCi of [14C]-rucaparib</description>
    <arm_group_label>C-14 labeled rucaparib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rucaparib</intervention_name>
    <description>200 &amp; 300 mg tablet</description>
    <arm_group_label>C-14 labeled rucaparib</arm_group_label>
    <other_name>CO-338</other_name>
    <other_name>Rubraca</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed advanced solid tumor&#xD;
&#xD;
          -  Part II only: Have a known deleterious BRCA1/2 mutation (germline or somatic) as&#xD;
             determined by a local or central laboratory&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Adequate bone marrow, renal, and liver function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy,&#xD;
             gene therapy, vaccine therapy, or angiogenesis inhibitors within 14 days prior to Day&#xD;
             1&#xD;
&#xD;
          -  Participation in a trial involving administration of [14C]-labeled compound(s) within&#xD;
             the last 6 months prior to Day 1&#xD;
&#xD;
          -  Arterial or venous thrombi (including cerebrovascular accident), myocardial&#xD;
             infarction, admission for unstable angina, cardiac angioplasty, or stenting within the&#xD;
             last 3 months prior to Screening&#xD;
&#xD;
          -  Pre-existing duodenal stent, recent or existing bowel obstruction, and/or any&#xD;
             gastrointestinal disorder or defect that would, in the opinion of the Investigator,&#xD;
             interfere with absorption of rucaparib&#xD;
&#xD;
          -  Untreated or symptomatic central nervous system (CNS) metastases&#xD;
&#xD;
          -  Evidence or history of bleeding disorder&#xD;
&#xD;
          -  Participation in another investigational drug trial within 14 days prior to Day 1 (or&#xD;
             5 times the half-life of the drug, whichever is longer) or exposure to more than three&#xD;
             new investigational agents within 12 months prior to Day 1&#xD;
&#xD;
          -  Acute illness (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to Day 1,&#xD;
             unless mild in severity and approved by the Investigator and Sponsor's/designated&#xD;
             medical representative&#xD;
&#xD;
          -  Active second malignancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>PRA Magyarország Kft.</name>
      <address>
        <city>Budapest</city>
        <state>Rottenbiller Utca 13</state>
        <zip>1077</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hungary</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>June 7, 2023</last_update_submitted>
  <last_update_submitted_qc>June 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>rucaparib</keyword>
  <keyword>CO-338</keyword>
  <keyword>Clovis</keyword>
  <keyword>Clovis Oncology</keyword>
  <keyword>PARP inhibitor</keyword>
  <keyword>Absorption</keyword>
  <keyword>Metabolism</keyword>
  <keyword>Excretion</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rucaparib</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/NCT02986100
org study id: CO-338-045
secondary id: 2015-004394-32
nct id: NCT02986100
lead sponsor: 
has dmc: No
The purpose of this study is to characterize the mass balance, absorption, metabolism, and
      elimination pathways of orally administered [14C] rucaparib followed by cycle by cycle
      treatment with rucaparib continuing until disease progression or other reason for
      discontinuation
This is a Phase 1, open-label, non-randomized, mass balance study in patients with
      histologically or cytologically confirmed advanced solid tumors. Approximately 6 patients
      will be enrolled. The study will consist of 2 parts: a mass balance part (Part I) and a
      rucaparib treatment part (Part II).

      Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140
      µCi) in the fasted state. Patients will be confined at the study site for the collection of
      blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be
      discharged sooner than Day 13, if the discharge criteria are met. If the cumulative recovery
      of radioactivity exceeds 90% of the administered dose or if radioactivity in urine and feces
      is < 1% of the administered dose over a 24 hour period on two consecutive days, as determined
      by quick counts.

      In Part II, the treatment with rucaparib in 28-day cycles will continue until progression of
      disease, unacceptable toxicity, or other reason for discontinuation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
masking description: Open Label
measure: Pharmacokinetics of 14C-labeled rucaparib (radioactivity in whole blood and plasma): tmax
time frame: Days 1-13
description: Time to peak concentration (tmax)
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): Cmax
time frame: Days 1-13
description: peak (maximum) concentration (Cmax)
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): t1/2
time frame: Days 1-13
description: Elimination half-life (t1/2)
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): AUC
time frame: Days 1-13
description: Area under curve (AUC)
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): CL/F
time frame: Days 1-13
description: Oral clearance (CL/F)
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): V/F
time frame: Days 1-13
description: Apparent volume of distribution (V/F)
measure: Excretion rate of 14C-labeled rucaparib(radioactivity in feces)
time frame: Days 1-13
description: Percent of dose excreted in feces
measure: Excretion rate of 14C-labeled rucaparib(radioactivity in urine)
time frame: Days 1-13
description: Percent of dose excreted in urine
measure: Pharmacokinetics of rucaparib (in urine): CLR
time frame: Days 1-13
description: Renal clearance (CLR)
measure: Excretion rate of 14C-labeled rucaparib(radioactivity in vomit, if applicable)
time frame: Days 1-13
description: Percent of dose in vomit, if applicable
measure: Metabolite identification of rucaparib in plasma, urine and feces
time frame: Days 1-13
measure: Cumulative whole blood:plasma ratio calculated for Cmax
time frame: Days 1-13
description: peak concentration (Cmax)
measure: Cumulative whole blood:plasma ratio calculated for AUC0-tlast
time frame: Day 1-13
description: AUC from time zero to the last time point with concentration above the lower limit of quantitation (AUC0-last)
measure: Cumulative whole blood:plasma ratio calculated for AUCinf
time frame: Day 1-13
description: AUC from time zero to infinity (AUCinf)
measure: Tolerability and safety of rucaparib assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications
time frame: From cycle 1 Day 1 until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks
description: Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications
measure: To evaluate the antitumor activity of rucaparib in BRCA mutated solid tumors based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
time frame: Cycle 1 Day 1 until progression of disease, unacceptable toxicity, or discontinuation for other reasons
description: Response will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and tumor markers per applicable criteria for a given tumor type
arm group label: C-14 labeled rucaparib
arm group type: Experimental
description: Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met.
After completion of Part I, patients with a deleterious BRCA mutation will have the option to participate in Part II by receiving 600 mg BID rucaparib tablets orally in 28 day cycles until disease progression, unacceptable toxicity, death, or discontinuation for other reasons
intervention type: Drug
intervention name: C-14 labeled Rucaparib
description: Each dosage unit consists of a hard gelatin capsule filled with cold rucaparib camsylate and [14C]-rucaparib camsylate salt. Each capsule contains approximately 150 mg rucaparib (free base weight) and approximately 35 µCi of [14C]-rucaparib. Each patient will ingest four capsules in the fasted state for a total dose of 600 mg rucaparib (free base weight) with approximately 140 µCi of [14C]-rucaparib
arm group label: C-14 labeled rucaparib
intervention type: Drug
intervention name: Rucaparib
description: 200 & 300 mg tablet
arm group label: C-14 labeled rucaparib
other name: CO-338
other name: Rubraca
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Hungary
responsible party type: Sponsor
mesh term: Rucaparib
sharing ipd: No