<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/NCT04457713</url>
  </required_header>
  <id_info>
    <org_study_id>Off Label Study protocol</org_study_id>
    <nct_id>NCT04457713</nct_id>
  </id_info>
  <brief_title>Off-label Use of Anti-cancer Drugs in Norway -a Prospective Cohort Study</brief_title>
  <official_title>Off-label Use of Anti-cancer Drugs in Norway -a Prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oslo University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Off-label drug use, where a marketed drug is used outside its approved indication, may allow&#xD;
      early access to new and promising treatments. However, its use can be a source of&#xD;
      controversy, due to limited evidence for clinical benefit and lack of cost/QALY-estimates,&#xD;
      leading to challenging prioritization issues. The number of drugs suitable for off-label use&#xD;
      is expected to further increase in the coming years, owing to the rapid progress in the field&#xD;
      of oncology, in particular with the current era of precision medicine and targeted therapies.&#xD;
      This also challenges the traditional method of running clinical trials, with eligible patient&#xD;
      populations commonly being small, underpinning the importance of gaining supplementary&#xD;
      real-world evidence from well performed observational studies.&#xD;
&#xD;
      This prospective observational study will therefore assess real-world outcomes of patients&#xD;
      treated with off-label anti-cancer drugs, including efficacy in terms of response rates, time&#xD;
      to progression/relapse measures and survival; patient-reported outcome measures (PROMS) and&#xD;
      self-reported side-effects/toxicity; as well as collecting blood samples for a biobank for&#xD;
      further translational research. Further, the study will give a descriptive analysis of the&#xD;
      current practice of off-label use of anti-cancer drugs in Norway, including prevalence&#xD;
      estimation and health care related cost analyses.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2027</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>2 Years</target_duration>
  <primary_outcome>
    <measure>Progression free survival (PFS).</measure>
    <time_frame>Assessed up to 2 years after end of inclusion</time_frame>
    <description>Time from date of inclusion until the date of first documented progression or date of death from any cause, whichever come first, according to RECIST v1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patients questionnaire EORTC QLQ-C30</measure>
    <time_frame>Assessed from inclusion until 2 years after end of treatment</time_frame>
    <description>Assessment of patients reported quality of life, as measured by EORTC QLC30</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective tumor response rate (ORR)</measure>
    <time_frame>Assed through study completion, an average of 1 year</time_frame>
    <description>Defined as the proportion of patients with an objective tumor response (either partial response [PR] or complete response [CR] using RECIST v1.1) response (DR), time to next treatment and overall survival (OS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DR)</measure>
    <time_frame>Assed through study completion, an average of 1 year</time_frame>
    <description>Duration of response among patients with an objective response, according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to next treatment (TTNT)</measure>
    <time_frame>Assed through study completion, an average of 1 year</time_frame>
    <description>Time from inclusion to institution og next therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Assessed up to 2 years after end of inclusion</time_frame>
    <description>Time from date of inclusion until the date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatigue</measure>
    <time_frame>From inclusion until 2 years after end of treatment</time_frame>
    <description>Assessment of patient reported outcomes, as measured by the Chalder Fatigue Questionnaire (FQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression</measure>
    <time_frame>From inclusion until 2 years after end of treatment</time_frame>
    <description>Assessment of patient reported outcomes, as measured by the patient health questionnaire (PHQ-9)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity</measure>
    <time_frame>From inclusion until 2 years after end of treatment</time_frame>
    <description>Assessment of patient reported outcomes, as measured by an 11 point Numerical Rating Scale (NRS) for pain intensity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event</measure>
    <time_frame>From inclusion until 2 years after end of treatment</time_frame>
    <description>Patients files and self-report. Classified according to CTCAE v 5.0 and MedDRA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality adjusted life years (QALYs)</measure>
    <time_frame>From inclusion until 2 years after end of treatment</time_frame>
    <description>Patient self reported EQ-5D</description>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Cancer</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Any patient accepted by the leadership in the Department of Oncology at OUH to receive&#xD;
        anti-cancer treatment off-label from the date of start of the study is eligible for&#xD;
        inclusion. Of note, this does not include off-label use of drugs used for supportive care.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Verified cancer diagnosis (based on radiological, histological/cytological or&#xD;
             operative evidence).&#xD;
&#xD;
          -  Treatment with off-label anti-cancer drug.&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  None&#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>Knut Smeland, PhD/MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oslo University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Knut Smeland, PhD/MD</last_name>
    <phone>+4722934000</phone>
    <email>knusme@ous-hf.no</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tormod Guren, PhD/MD</last_name>
    <phone>+4722934000</phone>
    <email>uxtour@ous-hf.no</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <zip>0379</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Knut Smeland, PhD/MD</last_name>
      <phone>+4722934000</phone>
      <email>knusme@ous-hf.no</email>
    </contact>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>September 8, 2021</last_update_submitted>
  <last_update_submitted_qc>September 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oslo University Hospital</investigator_affiliation>
    <investigator_full_name>Knut Halvor Bjøro Smeland</investigator_full_name>
    <investigator_title>Chief Attending Physician</investigator_title>
  </responsible_party>
  <keyword>Off Label Use</keyword>
  <!-- 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/NCT04457713
org study id: Off Label Study protocol
nct id: NCT04457713
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Off-label drug use, where a marketed drug is used outside its approved indication, may allow
      early access to new and promising treatments. However, its use can be a source of
      controversy, due to limited evidence for clinical benefit and lack of cost/QALY-estimates,
      leading to challenging prioritization issues. The number of drugs suitable for off-label use
      is expected to further increase in the coming years, owing to the rapid progress in the field
      of oncology, in particular with the current era of precision medicine and targeted therapies.
      This also challenges the traditional method of running clinical trials, with eligible patient
      populations commonly being small, underpinning the importance of gaining supplementary
      real-world evidence from well performed observational studies.

      This prospective observational study will therefore assess real-world outcomes of patients
      treated with off-label anti-cancer drugs, including efficacy in terms of response rates, time
      to progression/relapse measures and survival; patient-reported outcome measures (PROMS) and
      self-reported side-effects/toxicity; as well as collecting blood samples for a biobank for
      further translational research. Further, the study will give a descriptive analysis of the
      current practice of off-label use of anti-cancer drugs in Norway, including prevalence
      estimation and health care related cost analyses.
observational model: Cohort
time perspective: Prospective
measure: Progression free survival (PFS).
time frame: Assessed up to 2 years after end of inclusion
description: Time from date of inclusion until the date of first documented progression or date of death from any cause, whichever come first, according to RECIST v1.1
measure: Patients questionnaire EORTC QLQ-C30
time frame: Assessed from inclusion until 2 years after end of treatment
description: Assessment of patients reported quality of life, as measured by EORTC QLC30
measure: Objective tumor response rate (ORR)
time frame: Assed through study completion, an average of 1 year
description: Defined as the proportion of patients with an objective tumor response (either partial response [PR] or complete response [CR] using RECIST v1.1) response (DR), time to next treatment and overall survival (OS)
measure: Duration of response (DR)
time frame: Assed through study completion, an average of 1 year
description: Duration of response among patients with an objective response, according to RECIST v1.1
measure: Time to next treatment (TTNT)
time frame: Assed through study completion, an average of 1 year
description: Time from inclusion to institution og next therapy
measure: Overall survival (OS)
time frame: Assessed up to 2 years after end of inclusion
description: Time from date of inclusion until the date of death from any cause
measure: Fatigue
time frame: From inclusion until 2 years after end of treatment
description: Assessment of patient reported outcomes, as measured by the Chalder Fatigue Questionnaire (FQ)
measure: Depression
time frame: From inclusion until 2 years after end of treatment
description: Assessment of patient reported outcomes, as measured by the patient health questionnaire (PHQ-9)
measure: Pain intensity
time frame: From inclusion until 2 years after end of treatment
description: Assessment of patient reported outcomes, as measured by an 11 point Numerical Rating Scale (NRS) for pain intensity
measure: Adverse event
time frame: From inclusion until 2 years after end of treatment
description: Patients files and self-report. Classified according to CTCAE v 5.0 and MedDRA
measure: Quality adjusted life years (QALYs)
time frame: From inclusion until 2 years after end of treatment
description: Patient self reported EQ-5D
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Knut Smeland, PhD/MD
role: Principal Investigator
affiliation: Oslo University Hospital
last name: Knut Smeland, PhD/MD
phone: +4722934000
email: knusme@ous-hf.no
last name: Tormod Guren, PhD/MD
phone: +4722934000
email: uxtour@ous-hf.no
facility: 
status: Recruiting
contact: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: Oslo University Hospital
investigator full name: Knut Halvor Bjøro Smeland
investigator title: Chief Attending Physician