<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/NCT04455958</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00021444</org_study_id>
    <secondary_id>NCI-2020-02877</secondary_id>
    <secondary_id>STUDY00021444</secondary_id>
    <nct_id>NCT04455958</nct_id>
  </id_info>
  <brief_title>Lopinavir/Ritonavir for the Treatment of COVID-19 Positive Patients With Cancer and Immune Suppression in the Last Year</brief_title>
  <official_title>A Double-Blind, Randomized, Placebo-Controlled Phase II Study of Lopinavir/Ritonavir Versus Placebo in COVID-19 Positive Patients With Cancer and Immune Suppression in the Last Year</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>OHSU Knight 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 phase II trial studies how well lopinavir/ritonavir works in treating COVID-19 positive&#xD;
      patients with cancer and a weakened immune system (immune-suppression) in the last year and&#xD;
      have mild or moderate symptoms caused by COVID-19. Lopinavir/ritonavir may help to lessen or&#xD;
      prevent COVID-19 symptoms from getting worse in cancer patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine if treatment with lopinavir/ritonavir will decrease progression of symptoms&#xD;
      compared to control/placebo.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Determine if treatment improves time to symptom resolution. II. Determine the time to&#xD;
      symptom progression. III. Determine time to improvement of participants as defined by&#xD;
      complete resolution of symptoms.&#xD;
&#xD;
      IV. Determine the proportion of participants who have severe or critical symptoms and&#xD;
      hospital admission.&#xD;
&#xD;
      V. Determine the time to hospital admission for those who develop severe of critical symptoms&#xD;
      VI. Determine the proportion of participants with an intensive care unit (ICU) admission.&#xD;
&#xD;
      VII. Determine the proportion of participants receiving ventilator support. VIII. Determine&#xD;
      survival of participants enrolled on the study.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. For patients admitted to the hospital, will determine the following parameters: potassium&#xD;
      level, blood oxygen level, creatinine, and blood pressure.&#xD;
&#xD;
      II. Identify obstacles and barriers encountered while implementing a clinical trial in the&#xD;
      context of a pandemic caused by a contagious disease and associated social distancing.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 groups.&#xD;
&#xD;
      GROUP I: Patients receive lopinavir/ritonavir orally (PO) twice daily (BID) for 14 days in&#xD;
      the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      GROUP II: Patients receive placebo PO BID for 14 days in the absence of disease progression&#xD;
      or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up 3 times a week until symptoms&#xD;
      resolve plus 2 additional weeks thereafter, for up to 3 months, whichever occurs first.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    limited resources&#xD;
  </why_stopped>
  <start_date type="Anticipated">May 1, 2021</start_date>
  <completion_date type="Anticipated">November 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Severity of symptoms</measure>
    <time_frame>3 months</time_frame>
    <description>Will be compared to the time of randomization. The severity of symptoms will be categorized as mild, moderate, severe, or critical according to the grading of symptoms. The proportion of participants with progression to more severe symptoms between treatments groups will be compared using a Fisher's Exact test at a 0.05 significance level.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate of lopinavir/ritonavir</measure>
    <time_frame>3 months</time_frame>
    <description>Will be defined as improvement on symptoms: yes or no. Will be compared between treatment groups using log-rank test. A 95% confidence interval of treatment rate difference in symptom progression will be calculated by the Wald method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to symptom progression</measure>
    <time_frame>From randomization to the first documented symptoms progression, assessed up to 3 months</time_frame>
    <description>Will be compared between treatment groups using log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to improvement of participants</measure>
    <time_frame>From randomization to first documented complete resolution of symptoms, assessed up to 3 months</time_frame>
    <description>Will be compared between treatment groups using log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to hospital admission for those who develop severe of critical symptoms</measure>
    <time_frame>From time of randomization to the time of hospital admission, assessed up to 3 months</time_frame>
    <description>Will be compared between treatment groups using log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive care unit (ICU) admission: yes or no</measure>
    <time_frame>3 months</time_frame>
    <description>Will be compared using Fisher's exact test, and point and interval estimates will be provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Receiving ventilator support: yes or no</measure>
    <time_frame>3 months</time_frame>
    <description>Will be compared using Fisher's exact test, and point and interval estimates will be provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From randomization to death due to any cause, assessed up to 3 months</time_frame>
    <description>Will be compared using Fisher's exact test, and point and interval estimates will be provided.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Potassium level</measure>
    <time_frame>3 months</time_frame>
    <description>Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood oxygen level</measure>
    <time_frame>3 months</time_frame>
    <description>Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.</description>
  </other_outcome>
  <other_outcome>
    <measure>Creatinine level</measure>
    <time_frame>3 months</time_frame>
    <description>Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure</measure>
    <time_frame>3 months</time_frame>
    <description>Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.</description>
  </other_outcome>
  <other_outcome>
    <measure>Ability to remotely consent, monitor, and treat patients in the context of a pandemic of a contagious disease</measure>
    <time_frame>3 months</time_frame>
    <description>Will evaluate on a subjective basis the ability to remotely consent, monitor and treat patients in the context of a pandemic of a contagious disease. The proportion of participants able to be remotely consented, monitored, and treated in the context of a pandemic of a contagious disease will be tabulated and compared using the chi-square test.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <condition>Malignant Solid Neoplasm</condition>
  <condition>Symptomatic COVID-19 Infection Laboratory-Confirmed</condition>
  <arm_group>
    <arm_group_label>Group I (lopinavir/ritonavir)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive lopinavir/ritonavir PO BID for 14 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II (placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients receive placebo PO BID for 14 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lopinavir/Ritonavir</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Group I (lopinavir/ritonavir)</arm_group_label>
    <other_name>Kaletra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Administration</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Group II (placebo)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Group I (lopinavir/ritonavir)</arm_group_label>
    <arm_group_label>Group II (placebo)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Participants with a diagnostically proven COVID-19 positive nasal swab test result&#xD;
             within 14 days&#xD;
&#xD;
          -  Participants must have a diagnosis of cancer&#xD;
&#xD;
          -  Participants must be considered immune suppressed either due to their cancer diagnosis&#xD;
             or due to treatment of their cancer. Participants must meet at least one of the&#xD;
             following criteria:&#xD;
&#xD;
               -  Have received immune suppressing anti-cancer therapy in the past year (i.e.,&#xD;
                  therapy that suppresses white blood cells and/or has been shown to be associated&#xD;
                  with infection, as stipulated in the drug package insert)&#xD;
&#xD;
               -  Have received intravenous immunoglobulin (IVIG) in the past year for treatment&#xD;
                  and/or prevention of recurrent infections&#xD;
&#xD;
               -  Are within one year of an autologous bone marrow transplant or chimeric antigen&#xD;
                  receptor (CAR) T-cell therapy, or within five years of an allogeneic bone marrow&#xD;
                  transplant&#xD;
&#xD;
               -  Have been treated for three or more infections within the past 6 months&#xD;
&#xD;
               -  Have an absolute neutrophil count at or below 1,500 cells/mcL at some point&#xD;
                  within two months of the time of consent. This can be due therapy and/or due to&#xD;
                  cancer suppressing marrow function&#xD;
&#xD;
               -  Have a history of neutropenic fever in the past year&#xD;
&#xD;
               -  Presence of a chronic infection, e.g. tuberculosis (TB) or osteomyelitis, or&#xD;
                  within 3 months of treatment for such. Topical fungal infections of the skin are&#xD;
                  not included in this category&#xD;
&#xD;
          -  Participants with mild symptoms, must have had mild symptoms for no more than 2 weeks&#xD;
&#xD;
          -  Participants with moderate symptoms, must have had moderate symptoms for no more than&#xD;
             1 week&#xD;
&#xD;
          -  Pregnant or women of child-bearing potential may be treated if they have no documented&#xD;
             lopinavir-associated resistance substitutions&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =&lt; 3 x&#xD;
             upper limit of normal (ULN)&#xD;
&#xD;
          -  Total bilirubin =&lt; 2 x ULN (individuals with higher values felt to be consistent with&#xD;
             inborn errors of metabolism will be considered on a case-by-case basis)&#xD;
&#xD;
          -  Creatinine =&lt; 2 x ULN&#xD;
&#xD;
          -  Participants with abnormal blood counts (white blood cell [WBC], platelet, hemoglobin&#xD;
             [Hg]) will not be excluded&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who do not develop mild to moderate symptoms within 28 days of test&#xD;
             results&#xD;
&#xD;
          -  Participants with rapid clinical deterioration, in the opinion of the investigator&#xD;
&#xD;
          -  Participants experiencing severe symptoms according to COVID-19 Symptom Grading Tool&#xD;
&#xD;
          -  History of being human immunodeficiency virus (HIV) positive; by history only;&#xD;
             participants do not need to confirm by testing&#xD;
&#xD;
          -  Participant has any other concurrent severe and/or uncontrolled medical conditions&#xD;
             that would, in the investigator's judgment, may cause unacceptable safety risks,&#xD;
             contraindicate patient participation in the clinical study or compromise compliance&#xD;
             with the protocol&#xD;
&#xD;
          -  Participants receiving any contraindicated medication that in the opinion of the&#xD;
             investigator cannot be continued while receiving study drug and cannot be held for the&#xD;
             duration of the 14-day study treatment period safely&#xD;
&#xD;
          -  History of unstable cardiac disease in the past 6 months&#xD;
&#xD;
          -  History of prolonged QT interval, or on other cardiac medications known to prolong the&#xD;
             QT interval&#xD;
&#xD;
          -  Use of strong inhibitors and inducers of CYP3A4 is prohibited. Lopinavir/ritonavir&#xD;
             (L/R) is primarily metabolized by CYP3A4. Therefore, concomitant use of strong&#xD;
             inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, indinavir,&#xD;
             nelfinavir and saquinavir), and inducers of CYP3A (e.g. rifampin, phenytoin,&#xD;
             carbamazepine, phenobarbital, St. John's wort) are not permitted. The use of other&#xD;
             herbals will be reviewed on a case-by-case basis. If they are deemed to be strong&#xD;
             modulators of CYP3A4, patients will be excluded if they are unable or unwilling to&#xD;
             stop taking them&#xD;
&#xD;
          -  Women who plan to breast feed while on this study are not eligible for participation&#xD;
             due to the potential for unnecessary adverse event risks to a child&#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>Jennifer Saultz</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>April 22, 2021</last_update_submitted>
  <last_update_submitted_qc>April 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Jennifer Saultz</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Laboratory Infection</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Lopinavir</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04455958
org study id: STUDY00021444
secondary id: NCI-2020-02877
secondary id: STUDY00021444
nct id: NCT04455958
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well lopinavir/ritonavir works in treating COVID-19 positive
      patients with cancer and a weakened immune system (immune-suppression) in the last year and
      have mild or moderate symptoms caused by COVID-19. Lopinavir/ritonavir may help to lessen or
      prevent COVID-19 symptoms from getting worse in cancer patients.
PRIMARY OBJECTIVE:

      I. To determine if treatment with lopinavir/ritonavir will decrease progression of symptoms
      compared to control/placebo.

      SECONDARY OBJECTIVES:

      I. Determine if treatment improves time to symptom resolution. II. Determine the time to
      symptom progression. III. Determine time to improvement of participants as defined by
      complete resolution of symptoms.

      IV. Determine the proportion of participants who have severe or critical symptoms and
      hospital admission.

      V. Determine the time to hospital admission for those who develop severe of critical symptoms
      VI. Determine the proportion of participants with an intensive care unit (ICU) admission.

      VII. Determine the proportion of participants receiving ventilator support. VIII. Determine
      survival of participants enrolled on the study.

      EXPLORATORY OBJECTIVES:

      I. For patients admitted to the hospital, will determine the following parameters: potassium
      level, blood oxygen level, creatinine, and blood pressure.

      II. Identify obstacles and barriers encountered while implementing a clinical trial in the
      context of a pandemic caused by a contagious disease and associated social distancing.

      OUTLINE: Patients are randomized to 1 of 2 groups.

      GROUP I: Patients receive lopinavir/ritonavir orally (PO) twice daily (BID) for 14 days in
      the absence of disease progression or unacceptable toxicity.

      GROUP II: Patients receive placebo PO BID for 14 days in the absence of disease progression
      or unacceptable toxicity.

      After completion of study treatment, patients are followed up 3 times a week until symptoms
      resolve plus 2 additional weeks thereafter, for up to 3 months, whichever occurs first.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Severity of symptoms
time frame: 3 months
description: Will be compared to the time of randomization. The severity of symptoms will be categorized as mild, moderate, severe, or critical according to the grading of symptoms. The proportion of participants with progression to more severe symptoms between treatments groups will be compared using a Fisher's Exact test at a 0.05 significance level.
measure: Clinical benefit rate of lopinavir/ritonavir
time frame: 3 months
description: Will be defined as improvement on symptoms: yes or no. Will be compared between treatment groups using log-rank test. A 95% confidence interval of treatment rate difference in symptom progression will be calculated by the Wald method.
measure: Time to symptom progression
time frame: From randomization to the first documented symptoms progression, assessed up to 3 months
description: Will be compared between treatment groups using log-rank test.
measure: Time to improvement of participants
time frame: From randomization to first documented complete resolution of symptoms, assessed up to 3 months
description: Will be compared between treatment groups using log-rank test.
measure: Time to hospital admission for those who develop severe of critical symptoms
time frame: From time of randomization to the time of hospital admission, assessed up to 3 months
description: Will be compared between treatment groups using log-rank test.
measure: Intensive care unit (ICU) admission: yes or no
time frame: 3 months
description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.
measure: Receiving ventilator support: yes or no
time frame: 3 months
description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.
measure: Overall survival
time frame: From randomization to death due to any cause, assessed up to 3 months
description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.
measure: Potassium level
time frame: 3 months
description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.
measure: Blood oxygen level
time frame: 3 months
description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.
measure: Creatinine level
time frame: 3 months
description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.
measure: Blood pressure
time frame: 3 months
description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.
measure: Ability to remotely consent, monitor, and treat patients in the context of a pandemic of a contagious disease
time frame: 3 months
description: Will evaluate on a subjective basis the ability to remotely consent, monitor and treat patients in the context of a pandemic of a contagious disease. The proportion of participants able to be remotely consented, monitored, and treated in the context of a pandemic of a contagious disease will be tabulated and compared using the chi-square test.
arm group label: Group I (lopinavir/ritonavir)
arm group type: Experimental
description: Patients receive lopinavir/ritonavir PO BID for 14 days in the absence of disease progression or unacceptable toxicity.
arm group label: Group II (placebo)
arm group type: Placebo Comparator
description: Patients receive placebo PO BID for 14 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Lopinavir/Ritonavir
description: Given PO
arm group label: Group I (lopinavir/ritonavir)
other name: Kaletra
intervention type: Drug
intervention name: Placebo Administration
description: Given PO
arm group label: Group II (placebo)
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Group I (lopinavir/ritonavir)
arm group label: Group II (placebo)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Saultz
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Jennifer Saultz
investigator title: Principal Investigator
mesh term: COVID-19
mesh term: Laboratory Infection
mesh term: Neoplasms
mesh term: Ritonavir
mesh term: Lopinavir