<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/NCT01704703</url>
  </required_header>
  <id_info>
    <org_study_id>TTD-12-03</org_study_id>
    <secondary_id>2012-001955-38</secondary_id>
    <nct_id>NCT01704703</nct_id>
  </id_info>
  <brief_title>Study of FOLFIRI + Panitumumab Using Ultra-selection Technology of Patients With Stage IV Colorectal Cancer Refractory to Irinotecan Without Any Mutation on KRAS, PIK3Ca, BRAF and NRAS Genes Detected With Highly Sensitive Techniques</brief_title>
  <acronym>ULTRA</acronym>
  <official_title>Open Label Phase II Study of FOLFIRI + Panitumumab Using Ultra-selection Technology With Next Generation High Sensitivity Genotyping of Patients With Stage IV Colorectal Cancer Refractory to Irinotecan Without Any Mutation on KRAS, PIK3Ca, BRAF and NRAS Genes Detected With Highly Sensitive Techniques.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Open label Phase II study of FOLFIRI + Panitumumab using ultra-selection technology with next&#xD;
      generation high sensitivity genotyping of patients with stage IV colorectal cancer refractory&#xD;
      to irinotecan without any mutation on KRAS, PIK3Ca, BRAF and NRAS genes detected with highly&#xD;
      sensitive techniques.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (TRO)</measure>
    <time_frame>4 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>disease control rate (TCE)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of response (DR)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to response(THR)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to progression (THP)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to treatment failure (THF)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of stable disease (DEE)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (SLP)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (SG)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Stage IV Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FOLFIRI + panitumumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>panitumumab</intervention_name>
    <description>Panitumumab 6,0 mg/kg day 1 i.v. 60 min</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRI</intervention_name>
    <description>Irinotecan 180 mg/m2 day 1 i.v. 30-90 min Folinic acid 400 mg/ m2 day 1 i.v. 120 min 5-FU 400 mg/ m2 day 1 Bolus 5-FU 2.400 mg/ m2 day 1 i.v. 46 hours</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Competent to understand, sign and date an IEC-approved informed consent form.&#xD;
&#xD;
          2. Men or women 18 years of age or older at the time the written informed consent is&#xD;
             obtained.&#xD;
&#xD;
          3. Histologically confirmed metastatic adenocarcinoma of the colon or rectum Wild-Type&#xD;
             RAS (No mutation) with at least 1 measurable metastatic lesion following RECIST&#xD;
             criteria v 1.1 and initially irresectable (non suitable for radical surgery at the&#xD;
             inclusion time).&#xD;
&#xD;
          4. Obtention of DNA from tumor tissue blocks sent to central lab (ICO) that is amenable&#xD;
             for highly sensitive techniques&#xD;
&#xD;
          5. Previous irinotecan based chemotherapy +/- bevacizumab for metastatic CCR during at&#xD;
             least 6 weeks.&#xD;
&#xD;
          6. Irinotecan based chemotherapy does not need to be the most recent chemotherapy&#xD;
             administrated. There are no restrictions on numbers of treatments lines before study&#xD;
             inclusion.&#xD;
&#xD;
          7. Disease progression during irinotecan treatment or within 6 months after irinotecan&#xD;
             treatment.&#xD;
&#xD;
          8. Karnofsky status ≥ 70% .&#xD;
&#xD;
          9. Adequate bone marrow, hepatic, renal and metabolic functions,&#xD;
&#xD;
               1. Adequate bone marrow function: neutrophils ≥ 1.5x109/ L; platelets ≥ 100x109/L;&#xD;
                  hemoglobin ≥ 9g/dL.&#xD;
&#xD;
               2. Hepatic functions as follows: total bilirubin count ≤ 1.5 x ULN; ALAT and ASAT ≤&#xD;
                  2.5 x ULN (≤ 5 x ULN in case of liver metastasis).&#xD;
&#xD;
               3. Renal function: creatinine clearance &gt; 50 ml/min (according Cockcroft y Gault&#xD;
                  formulae)&#xD;
&#xD;
               4. Metabolic functions: magnesium ≥ lower limit of normal (LIN)&#xD;
&#xD;
         10. Life expectancy ≥ 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of&#xD;
             the skin or pre-invasive cervical cancer.&#xD;
&#xD;
          2. Unresolved toxicities from prior systemic therapy and/or radiotherapy that, in the&#xD;
             opinion of the investigator, does not qualify the patient for inclusion.&#xD;
&#xD;
          3. Documented or suspected central nervous system metastases.&#xD;
&#xD;
          4. Any previous antitumoral treatment (chemotherapy, hormonal therapy, radiation&#xD;
             treatment, surgery, immunotherapy, biologic therapy) ≤ 28 days before study inclusion.&#xD;
&#xD;
          5. Significant cardiovascular disease including unstable angina or myocardial infarction&#xD;
             within 12 months before initiating study treatment or a history of ventricular&#xD;
             arrhythmia.&#xD;
&#xD;
          6. Prior anti-EGFr antibody therapy (eg, Cetuximab) or treatment small molecule EGFr&#xD;
             tyrosine kinase inhibitors (eg, Erlotinib). Subjects who discontinue their first dose&#xD;
             of anti-EGFR therapy (Cetuximab) because of an infusion reaction may participate in&#xD;
             this clinical trial.&#xD;
&#xD;
          7. Paraffin-embedded tissue or unstained tumor slides from primary or metastatic tumor&#xD;
             not available or quality ADN not available for biomarker determination by highly&#xD;
             sensitive techniques.&#xD;
&#xD;
          8. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial&#xD;
             pneumonitis or pulmonary fibrosis.&#xD;
&#xD;
          9. Treatment for systemic infection within 14 days before study inclusion.&#xD;
&#xD;
         10. Acute or sub-acute intestinal occlusion and /or active inflammatory bowel disease or&#xD;
             other bowel disease causing chronic diarrhoea (defined as &gt; 4 loose stools per day).&#xD;
&#xD;
         11. History of Gilbert's syndrome or dihydropyrimidine deficiency.&#xD;
&#xD;
         12. History of any medical condition that may increase the risks associated with study&#xD;
             participation or may interfere with the interpretation of the study results.&#xD;
&#xD;
         13. Known positive test for human immunodeficiency virus infection, hepatitis C virus, and&#xD;
             chronic active hepatitis B infection.&#xD;
&#xD;
         14. Subject allergic to the ingredients of the study medication or to Staphylococcus&#xD;
             protein A.&#xD;
&#xD;
         15. Any co-morbid disease that would increase risk of toxicity.&#xD;
&#xD;
         16. Any kind of disorder that compromises the ability of the subject to give written&#xD;
             informed consent and/or comply with the study procedures.&#xD;
&#xD;
         17. Subject who is pregnant or breast feeding.&#xD;
&#xD;
         18. Surgery (excluding diagnostic biopsy or central venous catheter placement) ≤ 28 days&#xD;
             prior study inclusion.&#xD;
&#xD;
         19. Woman or man of childbearing potential not consenting to use adequate contraceptive&#xD;
             precautions.&#xD;
&#xD;
         20. Subject unwilling or unable to comply with study requirements.&#xD;
&#xD;
         21. Psychological, familial, sociological, or geographical condition potentially hampering&#xD;
             compliance with the study protocol and follow-up schedule.&#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>Ramón Salazar, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Institut Català d´Oncologia (ICO) L'Hospitalet</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gabriel Capella</last_name>
    <role>Study Chair</role>
    <affiliation>Institut Català d´Oncologia (ICO) L'Hospitalet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Spanish Cooperative Group for Digestive Tumour Therapy</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www.ttdgroup.org</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <last_update_submitted>July 31, 2017</last_update_submitted>
  <last_update_submitted_qc>July 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>colorectal cancer</keyword>
  <keyword>FOLFIRI</keyword>
  <keyword>Panitumumab</keyword>
  <keyword>KRAS, PIK3Ca,BRAF and NRAS genes</keyword>
  <keyword>highly sensitive techniques</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Panitumumab</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/NCT01704703
org study id: TTD-12-03
secondary id: 2012-001955-38
nct id: NCT01704703
lead sponsor: 
has dmc: No
Open label Phase II study of FOLFIRI + Panitumumab using ultra-selection technology with next
      generation high sensitivity genotyping of patients with stage IV colorectal cancer refractory
      to irinotecan without any mutation on KRAS, PIK3Ca, BRAF and NRAS genes detected with highly
      sensitive techniques.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (TRO)
time frame: 4 years
measure: disease control rate (TCE)
time frame: 4 years
measure: duration of response (DR)
time frame: 4 years
measure: time to response(THR)
time frame: 4 years
measure: time to progression (THP)
time frame: 4 years
measure: time to treatment failure (THF)
time frame: 4 years
measure: duration of stable disease (DEE)
time frame: 4 years
measure: Progression free survival (SLP)
time frame: 4 years
measure: Overall survival (SG)
time frame: 4 years
measure: Adverse events
time frame: 4 years
arm group label: Experimental
arm group type: Experimental
description: FOLFIRI + panitumumab
intervention type: Drug
intervention name: panitumumab
description: Panitumumab 6,0 mg/kg day 1 i.v. 60 min
arm group label: Experimental
intervention type: Drug
intervention name: FOLFIRI
description: Irinotecan 180 mg/m2 day 1 i.v. 30-90 min Folinic acid 400 mg/ m2 day 1 i.v. 120 min 5-FU 400 mg/ m2 day 1 Bolus 5-FU 2.400 mg/ m2 day 1 i.v. 46 hours
arm group label: Experimental
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ramón Salazar, MD, PhD
role: Study Chair
affiliation: Institut Català d´Oncologia (ICO) L'Hospitalet
last name: Gabriel Capella
role: Study Chair
affiliation: Institut Català d´Oncologia (ICO) L'Hospitalet
facility: 
country: Spain
url: http://www.ttdgroup.org
description: Related Info
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Hypersensitivity
mesh term: Panitumumab