<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/NCT03829410</url>
  </required_header>
  <id_info>
    <org_study_id>TROV-054</org_study_id>
    <nct_id>NCT03829410</nct_id>
  </id_info>
  <brief_title>Onvansertib in Combination With FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer Patients With a Kras Mutation</brief_title>
  <official_title>A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination With FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer in Patients With a Kras Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardiff Oncology</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cardiff Oncology</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>
      The purpose of the Phase 1b/2 study is to determine the safety and efficacy of Onvansertib,&#xD;
      administered orally, daily on Day 1-5 and Day 15-19 of each 28-day cycle, in combination with&#xD;
      FOLFIRI + Bevacizumab, as second-line treatment in adult participants who have metastatic&#xD;
      colorectal cancer with a Kras mutation. Participants must have histologically confirmed&#xD;
      metastatic and unresectable disease, and previously failed treatment or be intolerant to&#xD;
      fluoropyrimidine and oxaliplatin with or without bevacizumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 6, 2019</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Determine the Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants With Adverse Events (AEs)</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
    <description>The severity of each AE was graded using the Common Terminology Criteria for Adverse Events (CTCAE).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants with Clinically Significant Change From Baseline in Vital Signs</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants With Clinically Significant Change from Baseline in Electrocardiograms (ECG)</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants with Clinically Significant Physical Examination Findings</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants With Clinically Significant Change From Baseline in Body Weight</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1: Number of Participants With Change from Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
    <description>ECOG performance measured on-therapy. ECOG performance status was measured on a scale of 0-5, with higher scores indicating a worse outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Number of Participants with an Objective Response Rate (ORR)</measure>
    <time_frame>Baseline up to approximately 1 year after last dose of study drug (up to 42 months)</time_frame>
    <description>The ORR is determined by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) in participants who receive at least 1 cycle (28 days) of onvansertib in combination with FOLFIRI and bevacizumab. The response rate calculates the percentage of participants having a complete response or partial response during treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Disease Control Rate (DCR)</measure>
    <time_frame>Baseline up to approximately 1 year after last dose of study drug (up to 42 months)</time_frame>
    <description>Defined as complete response (CR) plus partial response (PR) plus stable disease (SD).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Number of Participants Who Experience an Adverse Event (AE)</measure>
    <time_frame>Baseline up to 28 days after last dose of study drug (up to 30 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Number of Participants with Progression-free Survival (PFS)</measure>
    <time_frame>Baseline up to approximately 1 year after last dose of study drug (up to 42 months)</time_frame>
    <description>Time from first drug administration to progression or death, whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Duration of Response (DoR)</measure>
    <time_frame>Baseline up to approximately 1 year after last dose of study drug (up to 42 months)</time_frame>
    <description>Defined from the date of first response (CR or PR) to progressive disease (PD) or death, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Overall Survival (OS)</measure>
    <time_frame>Baseline up to approximately 1 year after last dose of study drug (up to 42 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Number of Participants with a Reduction in Kras Allelic Burden on Liquid Biopsies</measure>
    <time_frame>Day 1 of each course up to 28 days after last dose of study drug (up to 30 months)</time_frame>
    <description>Blood samples obtained at baseline and subsequent time points will be analyzed for the presence of circulating tumor DNA (ctDNA [including Kras mutations]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Maximal Plasma Concentration (Cmax) of Onvansertib</measure>
    <time_frame>Pre-dose on Day 1 and 2-4 hours post-dose on Day 5 of Cycles 1, 3 and 5 (cycle is 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Time to Maximal Plasma Concentration (Tmax) of Onvansertib</measure>
    <time_frame>Pre-dose on Day 1 and 2-4 hours post-dose on Day 5 of Cycles 1, 3 and 5 (cycle is 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Onvansertib</measure>
    <time_frame>Pre-dose on Day 1 and 2-4 hours post-dose on Day 5 of Cycles 1, 3 and 5 (cycle is 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Onvansertib</measure>
    <time_frame>Pre-dose on Day 1 and 2-4 hours post-dose on Day 5 of Cycles 1, 3 and 5 (cycle is 28 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <condition>KRAS Gene Mutation</condition>
  <arm_group>
    <arm_group_label>Onvansertib + FOLFIRI + Bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1b: Onvansertib escalating starting dose of 12 mg/m^2 orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combination with FOLFIRI (180 mg/m^2 irinotecan, 400 mg/m^2 leucovorin, 400 mg/m^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m^2 continuous intravenous infusion 5-FU + 5 mg/kg bevacizumab. This Phase 1b portion of the study has been completed.&#xD;
Phase 2: Onvansertib Recommended Phase 2 Dose (RP2D) of 15 mg/m^2 orally Day 1 through Day 5 and Day 15 through Day 19 of every 28-day cycle in combination with FOLFIRI (180 mg/m^2 irinotecan, 400 mg/m^2 leucovorin, 400 mg/m^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m^2 continuous intravenous infusion 5-FU + 5 mg/kg bevacizumab, with treatment modifications or delays based on unresolved toxicity experienced during a previous cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Onvansertib</intervention_name>
    <description>Onvansertib orally.</description>
    <arm_group_label>Onvansertib + FOLFIRI + Bevacizumab</arm_group_label>
    <other_name>PCM-075</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Bevacizumab intravenously.</description>
    <arm_group_label>Onvansertib + FOLFIRI + Bevacizumab</arm_group_label>
    <other_name>Avastin®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRI</intervention_name>
    <description>FOLFIRI intravenously.</description>
    <arm_group_label>Onvansertib + FOLFIRI + Bevacizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed metastatic and unresectable colorectal cancer (CRC).&#xD;
&#xD;
          2. Documentation of a Kras mutation in exon 2, 3 or 4 in primary tumor or metastasis,&#xD;
             assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.&#xD;
             Participants with concomitant Kras and BRAF-V600 mutations are excluded from this&#xD;
             study. Participants with Microsatellite Instability High/Deficient Mismatch Repair&#xD;
             (MSI-H/ddMMR) are also ineligible for enrollment in this study.&#xD;
&#xD;
          3. Formalin-fixed, paraffin-embedded (FFPE) tumor tissue must be available for submission&#xD;
             to a central laboratory in order for a participant to be eligible. If no archival&#xD;
             tissue biopsy is available the participant must have a biopsy obtained at screening.&#xD;
&#xD;
          4. Age ≥ 18 years.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          6. Signed informed consent for participation in the study.&#xD;
&#xD;
          7. Participant is not receiving any other standard-of-care or experimental cancer&#xD;
             therapy. Participants participating in non-interventional surveys or observational&#xD;
             studies are allowed.&#xD;
&#xD;
          8. Has failed treatment or is intolerant of fluoropyrimidine and oxaliplatin with or&#xD;
             without bevacizumab.&#xD;
&#xD;
        8a. Participants must have had systemic therapy within 180 days of the screening visit, but&#xD;
        can have no anti-cancer therapy within 28 days of the planned first day of treatment on&#xD;
        study.&#xD;
&#xD;
        8b. Participants must have received oxaliplatin based chemotherapy with or without&#xD;
        bevacizumab (&gt;6 weeks in duration). Participants who received maintenance therapy with&#xD;
        fluoropyrimidines are eligible with or without re-challenge with oxaliplatin in combination&#xD;
        with fluoropyrimidines.&#xD;
&#xD;
        8c. Participants who received oxaliplatin/fluoropyrimidine-based neoadjuvant or adjuvant&#xD;
        therapy and have disease recurrence or progression &gt; 6 months from their last dose of&#xD;
        neoadjuvant or adjuvant treatment (or &gt; 6 months from surgery if no adjuvant therapy was&#xD;
        administered) will be required to have received fluoropyrimidine/oxaliplatin-based therapy&#xD;
        with or without bevacizumab as first-line treatment for metastatic disease.&#xD;
&#xD;
        8d. Participants must not have received prior irinotecan. 8e. For participants with rectal&#xD;
        cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen&#xD;
        for advanced disease.&#xD;
&#xD;
        8f. Participants who discontinued first-line therapy because of toxicity are eligible for&#xD;
        as long as progression occurred &lt; 6 months after the last dose of first-line therapy.&#xD;
&#xD;
        9. Chemotherapy regimen of irinotecan, fluorouracil [5-FU], and leucovorin (FOLFIRI)&#xD;
        therapy is appropriate for the participant as determined by the Investigator.&#xD;
&#xD;
        10. For a woman of child-bearing potential (WOCBP) or a male with a female partner who is a&#xD;
        WOCBP: must have a negative serum or urine pregnancy test within 5 days prior to&#xD;
        enrollment.&#xD;
&#xD;
        10a. WOCBP include any female who has experienced menarche and who has not undergone&#xD;
        successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral&#xD;
        oophorectomy) or is not postmenopausal (defined as amenorrhea &gt; 12 consecutive months); or&#xD;
        women on hormone replacement therapy (HRT) with documented serum follicle stimulating&#xD;
        hormone (FSH) level &gt; 35 mIU/mL. Even women who are using oral, implanted or injectable&#xD;
        contraceptive hormones or mechanical products such as an intrauterine device (IUD) or&#xD;
        barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing&#xD;
        abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of&#xD;
        child-bearing potential.&#xD;
&#xD;
        11. Imaging computed tomography (CT)/ magnetic resonance imaging (MRI) of&#xD;
        chest/abdomen/pelvis or other scans as necessary to document all sites of disease performed&#xD;
        within 21 days prior to enrollment. Only participant with measurable disease as defined per&#xD;
        Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) are eligible for&#xD;
        enrollment. CT is the preferred imaging modality, but MRI is also accepted.&#xD;
&#xD;
        12. Must have acceptable organ function. 13. Participant must consent to provision of, and&#xD;
        Investigator(s) must confirm access to and agree to submit a representative, formalin&#xD;
        fixed, paraffin block of tumor tissue to be used for correlative marker assays. Submission&#xD;
        of the tissue does not have to occur prior to enrollment.&#xD;
&#xD;
        14. Signed informed consent to provide blood sample(s) for specific correlative assays.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant Kras and BRAF-V600 mutations or MSI-H/dMMR&#xD;
&#xD;
          2. Anti-cancer chemotherapy or biologic therapy administered within 28 days prior to the&#xD;
             first dose of study drug. The exception is a single dose of radiation up to 8 Gray&#xD;
             (equal to 800 RAD) with palliative intent for pain control up to 14 days before&#xD;
             randomization.&#xD;
&#xD;
          3. More than one prior chemotherapy regimen administered in the metastatic setting.&#xD;
&#xD;
          4. Major surgery within 6 weeks prior to enrollment.&#xD;
&#xD;
          5. Untreated or symptomatic brain metastasis.&#xD;
&#xD;
          6. Women who are pregnant or breastfeeding.&#xD;
&#xD;
          7. Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would&#xD;
             significantly impede the absorption of an oral agent (e.g., intestinal occlusion,&#xD;
             active Crohn's disease, ulcerative colitis, extensive gastric and small intestine&#xD;
             resection).&#xD;
&#xD;
          8. Unable or unwilling to swallow study drug.&#xD;
&#xD;
          9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, clinically significant non-healing or healing wounds, symptomatic&#xD;
             congestive heart failure (CHF) Class II or higher according to the New York Heart&#xD;
             Association (NYHA) Functional Classification, unstable angina pectoris, clinically&#xD;
             significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at&#xD;
             rest or mild exertion), uncontrolled infection or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirements.&#xD;
&#xD;
        9a. Known active infection with Human Immunodeficiency Virus (HIV), with measurable viral&#xD;
        titer, and/or active infection with hepatitis B or C (participants who have had a hepatitis&#xD;
        B virus [HBV] immunization are eligible).&#xD;
&#xD;
        9b. Known active infection with SARS-CoV-2. 9c. Clinically significant ascites or pleural&#xD;
        effusions. 10. Known hypersensitivity to 5-FU/leucovorin. 11. Known hypersensitivity to&#xD;
        irinotecan. 12. Abnormal glucuronidation of bilirubin: known Gilbert's syndrome. 13.&#xD;
        Participants with a history of other malignancies except: adequately treated non-melanoma&#xD;
        skin cancer, curatively treated in-situ cancer of the cervix or prostate, or other solid&#xD;
        tumors curatively treated with no evidence of disease for &gt; 2 years.&#xD;
&#xD;
        14. Any active disease condition that would render the protocol treatment dangerous or&#xD;
        impair the ability of the participant to receive study drug.&#xD;
&#xD;
        15. Planned concomitant use of medications known to prolong the QT/QTc interval according&#xD;
        to institutional guidelines.&#xD;
&#xD;
        16. Presence of risk factors for torsade de pointes, including family history of Long QT&#xD;
        Syndrome or uncorrected hypokalemia.&#xD;
&#xD;
        17. The following are exclusion criteria for bevacizumab: 17a. History of cardiac disease:&#xD;
        CHF Class II or higher according to the New York Heart Association (NYHA); active coronary&#xD;
        artery disease, myocardial infarction within 6 months prior to study entry; unevaluated new&#xD;
        onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac&#xD;
        arrhythmias requiring anti arrhythmic therapy (beta blockers or digoxin are permitted).&#xD;
&#xD;
        17b. Current uncontrolled hypertension (systolic blood pressure [BP] &gt; 150 mmHg or&#xD;
        diastolic pressure &gt; 90 mmHg despite optimal medical management) and prior history of&#xD;
        hypertensive crisis or hypertensive encephalopathy.&#xD;
&#xD;
        17c. History of arterial thrombotic or embolic events (within 6 months prior to study&#xD;
        entry).&#xD;
&#xD;
        17d. Significant vascular disease (e.g., aortic aneurysm, aortic dissection, symptomatic&#xD;
        peripheral vascular disease).&#xD;
&#xD;
        17e. Evidence of bleeding diathesis or clinically significant coagulopathy. 17f. Major&#xD;
        surgical procedure (including open biopsy, significant traumatic injury, etc.) within 28&#xD;
        days, or anticipation of the need for major surgical procedure during the study, and minor&#xD;
        surgical procedure (excluding placement of a vascular access device) within 7 days prior to&#xD;
        study enrollment.&#xD;
&#xD;
        17g. Proteinuria at Screening as demonstrated by urinalysis with proteinuria ≥ 2+&#xD;
        (participants discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should&#xD;
        undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be&#xD;
        eligible).&#xD;
&#xD;
        17h. Abdominal fistula, GI perforation, peptic ulcer, or intra-abdominal abscess within the&#xD;
        past 6 months.&#xD;
&#xD;
        17i. Ongoing serious, non-healing wound, ulcer, or bone fracture. 17j. Known&#xD;
        hypersensitivity to any component of bevacizumab. 17k. History of reversible posterior&#xD;
        leukoencephalopathy syndrome (RPLS). 18. Use of strong CYP3A4 or UGT1A1 inhibitors or&#xD;
        strong CYP3A4 inducers. Participants currently receiving these agents who are able to&#xD;
        switch to alternate therapy are not excluded. Inhibitors should be stopped at least 1 week&#xD;
        prior to the first dose of protocol therapy and inducers should be stopped at least 2 weeks&#xD;
        prior to initiation of protocol therapy.&#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>Mayo Clinic Cancer Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CARTI Cancer Center</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center Research Institute</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Schar Cancer Institute</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>May 16, 2023</last_update_submitted>
  <last_update_submitted_qc>May 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Kras mutation</keyword>
  <keyword>PCM-075</keyword>
  <keyword>Onvansertib</keyword>
  <keyword>FOLFIRI</keyword>
  <keyword>Irinotecan</keyword>
  <keyword>5-Fluorouracil</keyword>
  <keyword>Leucovorin</keyword>
  <keyword>Avastin</keyword>
  <keyword>Bevacizumab</keyword>
  <keyword>PLK1</keyword>
  <keyword>PLK Inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Onvansertib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03829410
org study id: TROV-054
nct id: NCT03829410
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the Phase 1b/2 study is to determine the safety and efficacy of Onvansertib,
      administered orally, daily on Day 1-5 and Day 15-19 of each 28-day cycle, in combination with
      FOLFIRI + Bevacizumab, as second-line treatment in adult participants who have metastatic
      colorectal cancer with a Kras mutation. Participants must have histologically confirmed
      metastatic and unresectable disease, and previously failed treatment or be intolerant to
      fluoropyrimidine and oxaliplatin with or without bevacizumab.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Determine the Maximum Tolerated Dose (MTD)
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
measure: Phase 1: Number of Participants With Adverse Events (AEs)
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
description: The severity of each AE was graded using the Common Terminology Criteria for Adverse Events (CTCAE).
measure: Phase 1: Number of Participants with Clinically Significant Change From Baseline in Vital Signs
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
measure: Phase 1: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
measure: Phase 1: Number of Participants With Clinically Significant Change from Baseline in Electrocardiograms (ECG)
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
measure: Phase 1: Number of Participants with Clinically Significant Physical Examination Findings
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
measure: Phase 1: Number of Participants With Clinically Significant Change From Baseline in Body Weight
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
measure: Phase 1: Number of Participants With Change from Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
description: ECOG performance measured on-therapy. ECOG performance status was measured on a scale of 0-5, with higher scores indicating a worse outcome.
measure: Phase 2: Number of Participants with an Objective Response Rate (ORR)
time frame: Baseline up to approximately 1 year after last dose of study drug (up to 42 months)
description: The ORR is determined by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) in participants who receive at least 1 cycle (28 days) of onvansertib in combination with FOLFIRI and bevacizumab. The response rate calculates the percentage of participants having a complete response or partial response during treatment.
measure: Phase 2: Disease Control Rate (DCR)
time frame: Baseline up to approximately 1 year after last dose of study drug (up to 42 months)
description: Defined as complete response (CR) plus partial response (PR) plus stable disease (SD).
measure: Phase 2: Number of Participants Who Experience an Adverse Event (AE)
time frame: Baseline up to 28 days after last dose of study drug (up to 30 months)
measure: Phase 2: Number of Participants with Progression-free Survival (PFS)
time frame: Baseline up to approximately 1 year after last dose of study drug (up to 42 months)
description: Time from first drug administration to progression or death, whichever comes first.
measure: Phase 2: Duration of Response (DoR)
time frame: Baseline up to approximately 1 year after last dose of study drug (up to 42 months)
description: Defined from the date of first response (CR or PR) to progressive disease (PD) or death, whichever occurs first.
measure: Phase 2: Overall Survival (OS)
time frame: Baseline up to approximately 1 year after last dose of study drug (up to 42 months)
measure: Phase 2: Number of Participants with a Reduction in Kras Allelic Burden on Liquid Biopsies
time frame: Day 1 of each course up to 28 days after last dose of study drug (up to 30 months)
description: Blood samples obtained at baseline and subsequent time points will be analyzed for the presence of circulating tumor DNA (ctDNA [including Kras mutations]).
measure: Phase 2: Maximal Plasma Concentration (Cmax) of Onvansertib
time frame: Pre-dose on Day 1 and 2-4 hours post-dose on Day 5 of Cycles 1, 3 and 5 (cycle is 28 days)
measure: Phase 2: Time to Maximal Plasma Concentration (Tmax) of Onvansertib
time frame: Pre-dose on Day 1 and 2-4 hours post-dose on Day 5 of Cycles 1, 3 and 5 (cycle is 28 days)
measure: Phase 2: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Onvansertib
time frame: Pre-dose on Day 1 and 2-4 hours post-dose on Day 5 of Cycles 1, 3 and 5 (cycle is 28 days)
measure: Phase 2: Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Onvansertib
time frame: Pre-dose on Day 1 and 2-4 hours post-dose on Day 5 of Cycles 1, 3 and 5 (cycle is 28 days)
arm group label: Onvansertib + FOLFIRI + Bevacizumab
arm group type: Experimental
description: Phase 1b: Onvansertib escalating starting dose of 12 mg/m^2 orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combination with FOLFIRI (180 mg/m^2 irinotecan, 400 mg/m^2 leucovorin, 400 mg/m^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m^2 continuous intravenous infusion 5-FU + 5 mg/kg bevacizumab. This Phase 1b portion of the study has been completed.
Phase 2: Onvansertib Recommended Phase 2 Dose (RP2D) of 15 mg/m^2 orally Day 1 through Day 5 and Day 15 through Day 19 of every 28-day cycle in combination with FOLFIRI (180 mg/m^2 irinotecan, 400 mg/m^2 leucovorin, 400 mg/m^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m^2 continuous intravenous infusion 5-FU + 5 mg/kg bevacizumab, with treatment modifications or delays based on unresolved toxicity experienced during a previous cycle.
intervention type: Drug
intervention name: Onvansertib
description: Onvansertib orally.
arm group label: Onvansertib + FOLFIRI + Bevacizumab
other name: PCM-075
intervention type: Biological
intervention name: Bevacizumab
description: Bevacizumab intravenously.
arm group label: Onvansertib + FOLFIRI + Bevacizumab
other name: Avastin®
intervention type: Drug
intervention name: FOLFIRI
description: FOLFIRI intravenously.
arm group label: Onvansertib + FOLFIRI + Bevacizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Bevacizumab
mesh term: Onvansertib
sharing ipd: Undecided