<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/NCT03795272</url>
  </required_header>
  <id_info>
    <org_study_id>ENGOT-Cx7-NSGO/MaRuC</org_study_id>
    <nct_id>NCT03795272</nct_id>
  </id_info>
  <brief_title>Rucaparib Maintenance Therapy in Advanced Cervical Cancer</brief_title>
  <acronym>MaRuC</acronym>
  <official_title>A Randomized Double-blind Placebo-controlled Phase II Trial of Rucaparib Maintenance Therapy for Patients With Locally Advanced Cervical Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nordic Society of Gynaecological Oncology - Clinical Trials Unit</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institute of Cancer Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Central and Eastern European Oncology Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>North Eastern German Society of Gynaecological Oncology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Belgian Gynaecological Oncology Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Princess Margaret Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>PGOG (Polish Gynaecologic Oncology Group)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>GSO Global Clinical Research BV</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>GCP-enhederne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nordic Society of Gynaecological Oncology - Clinical Trials Unit</source>
  <oversight_info>
    <has_dmc>Yes</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>
      To evaluate the efficacy of PARP inhibitor, rucaparib as maintenance therapy for locally&#xD;
      advanced cervical cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The use of concomitant cisplatin-based chemo-radiation for cervical cancer has improved&#xD;
      survival of locally advanced cervical cancer patients and has become the standard of care. A&#xD;
      meta-analysis revealed that the addition of concurrent chemotherapy to radiation increased&#xD;
      the 5-year overall survival rate by 6% (HR 0.81: 60 vs 66%), and 5-year disease-free survival&#xD;
      rate by 8%, though there is still considerable need for improvement as most patients who&#xD;
      relapse are incurable. The unmet need is particularly higher in patients that are at high&#xD;
      risk of recurrence. The main negative prognostic factors are higher FIGO stage as well as the&#xD;
      presence of positive lymph nodes. Current studies are evaluating role of adjuvant&#xD;
      chemotherapy following chemo-radiation in locally advanced disease and will possibly improve&#xD;
      survival by reducing risk of distant metastases, however at the cost of excessive toxicity.&#xD;
&#xD;
      PARP inhibitors have shown considerable clinical benefit especially in platinum-sensitive&#xD;
      relapsed ovarian cancer. Several PARP inhibitors have been evaluated in other gynaecological&#xD;
      malignancies and three PARP inhibitors (olaparib, rucaparib &amp; niraparib) are approved by&#xD;
      European Medicines Agency and Food &amp; Drug Administration for treatment or as maintenance&#xD;
      therapy in ovarian cancer. Human papillomavirus causes oxidative stress that may result in&#xD;
      DNA single-strand breaks. In cervical cancer PARP-1 expression/activity may be up-regulated&#xD;
      in response to the ongoing oxidative stress (HPV and inflammation), and this may promote&#xD;
      progression. This may create a vicious circle of inflammation, PARP activation, NAD+&#xD;
      consumption, adenosine triphosphate consumption, necrosis, and inflammation. PARPi may limit&#xD;
      the role of PARP-1 in promoting inflammation and oxidative stress. There is theoretical&#xD;
      plausibility that PARPi may have a role in the treatment of cervical carcinoma.&#xD;
&#xD;
      This phase II randomized placebo-controlled double-blind study will evaluate the efficacy and&#xD;
      safety of rucaparib as adjuvant treatment for patients with locally advanced cervical cancer&#xD;
      who are responding to chemo-radiation. This investigator-initiated study will be performed&#xD;
      within the GCIG/ENGOT collaboration&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of financial support&#xD;
  </why_stopped>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Actual">October 10, 2019</completion_date>
  <primary_completion_date type="Actual">October 10, 2019</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>
    <intervention_model_description>This is a multicentre, phase 2, double-blind, placebo-controlled trial of maintenance rucaparib to obtain evidence of clinical benefit of rucaparib in locally advanced cervical cancer.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>double-blinded placebo-controlled</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-Free Survival in months</measure>
    <time_frame>42 months</time_frame>
    <description>the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival in Sub-Population in months</measure>
    <time_frame>42 months</time_frame>
    <description>the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first for the predefined study subgroups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Reported Outcomes</measure>
    <time_frame>42 months</time_frame>
    <description>Quality of Life Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival in months</measure>
    <time_frame>60 months</time_frame>
    <description>the time from randomization until the date of death by any cause</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>Rucaparib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with active oral drug, Rucaparib twice daily for 24 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will be treated with oral placebo twice daily for 24 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rucaparib</intervention_name>
    <description>2:1 randomization to receive rucaparib/placebo twice daily for 24 month</description>
    <arm_group_label>Rucaparib</arm_group_label>
    <other_name>active maintenance</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>matched placebo maintenance</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed squamous cell, adenocarcinoma or adenosquamous carcinoma of&#xD;
             the cervix.&#xD;
&#xD;
          2. Patient must have completed definitive chemoradiation and is evaluated to be in&#xD;
             complete remission 10-12 week's post definitive treatment.&#xD;
&#xD;
          3. Initial FIGO stage IIB with positive nodes (histological verification or verified by&#xD;
             MRI/PET-CT), FIGO stages IIIA, IIIB, IVA; or any stage with para-aortic metastases&#xD;
             (including IB and IIA with positive aortic nodes).&#xD;
&#xD;
          4. Toxicities resulting from definitive treatment must resolve to grade ≤1 prior to&#xD;
             randomization.&#xD;
&#xD;
          5. Patient must consent that archival tumour tissue can be collected at the time of&#xD;
             screening and used for translational studies.&#xD;
&#xD;
          6. Patient must consent to collection of whole blood and blood plasma during the study&#xD;
             period. These samples will be stored and later used for translational studies.&#xD;
&#xD;
          7. Patient agrees to undergo all analysis; radiological examinations according to&#xD;
             protocol.&#xD;
&#xD;
          8. The patient agrees to complete PROs (QoL questionnaire) during study treatment.&#xD;
&#xD;
          9. Patients must give informed consent.&#xD;
&#xD;
         10. Patients must be at least 18 years of age.&#xD;
&#xD;
         11. ECOG performance status 0-1&#xD;
&#xD;
         12. Serum albumin &gt;30g/l.&#xD;
&#xD;
         13. Adequate organ function&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥1,500/mcL&#xD;
&#xD;
               -  Platelets &gt;100,000/mcL&#xD;
&#xD;
               -  Haemoglobin ≥ 9g/dl (no blood transfusions for 4 weeks prior entering the trial.)&#xD;
&#xD;
               -  Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine&#xD;
                  clearance ≥50mL/min using Cockcroft-Gault formula.&#xD;
&#xD;
               -  Total bilirubin ≤1.5x ULN.&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) ≤2.5x ULN&#xD;
&#xD;
         14. Life expectancy of at least 12 weeks.&#xD;
&#xD;
         15. Women of childbearing potential must use highly effective methods of birth control for&#xD;
             the duration of study participation and for 6 months afterwards.&#xD;
&#xD;
         16. All patients: Patients should not donate blood or blood components while participating&#xD;
             in this study and through 90 days after receipt of the final dose of IMP. -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histological types other than in inclusion criteria, like sarcomas, small cell&#xD;
             carcinoma with neuroendocrine differentiation, non-epithelial cancers.&#xD;
&#xD;
          2. Concurrent cancer therapies or cancer therapy (chemotherapy, radiotherapy, surgery,&#xD;
             immunotherapy, biologic or hormonal therapy) within last 4 weeks.&#xD;
&#xD;
          3. Concurrent treatment with an investigational agent or participation in another&#xD;
             clinical trial.&#xD;
&#xD;
          4. Previous malignant disease: patients are not eligible for the study if actively being&#xD;
             treated of invasive cancer. Patients with previous malignant disease who are&#xD;
             relapse-free and treatment-free for more than three years may enter this study.&#xD;
             Patients with previous history of in-situ carcinoma of cervix, or non-invasive basal&#xD;
             cell and squamous cell skin carcinoma can enter this trial.&#xD;
&#xD;
          5. Active infections or other serious underlying significant medical illness, abnormal&#xD;
             laboratory finding or psychiatric illness/social situation that would, in the&#xD;
             investigator's judgment, make the patient inappropriate for this study. Known active&#xD;
             or chronic hepatitis C and/or B infection. Has known history of tuberculosis.&#xD;
&#xD;
          6. Gastrointestinal disorders or abnormalities that would interfere with absorption of&#xD;
             the study drug.&#xD;
&#xD;
          7. Any evidence of distant metastases.&#xD;
&#xD;
          8. Significant cardiovascular diseases, including uncontrolled hypertension, clinically&#xD;
             relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months&#xD;
             prior to randomization, congestive heart failure &gt;NYHA II (New York Heart&#xD;
             Association), severe peripheral vascular disease, clinically significant pericardial&#xD;
             effusion.&#xD;
&#xD;
          9. Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling&#xD;
             to use a medically acceptable method of contraception for the duration of the trial&#xD;
             and for 6 months afterwards.&#xD;
&#xD;
         10. Known hypersensitivity to the trial drugs, or to their excipients.&#xD;
&#xD;
         11. Persons who have been committed to an institution by official or judicial order&#xD;
&#xD;
         12. Patients with dependency on the sponsor, investigator or study site -&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <state>Sjaelland</state>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>København Ø</city>
        <state>Sjaelland</state>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>November 3, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>October 30, 2019</last_update_submitted>
  <last_update_submitted_qc>October 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cervical cancer</keyword>
  <keyword>rucaparib</keyword>
  <keyword>maintenance therapy</keyword>
  <keyword>placebo-controlled</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rucaparib</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/NCT03795272
org study id: ENGOT-Cx7-NSGO/MaRuC
nct id: NCT03795272
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To evaluate the efficacy of PARP inhibitor, rucaparib as maintenance therapy for locally
      advanced cervical cancer
The use of concomitant cisplatin-based chemo-radiation for cervical cancer has improved
      survival of locally advanced cervical cancer patients and has become the standard of care. A
      meta-analysis revealed that the addition of concurrent chemotherapy to radiation increased
      the 5-year overall survival rate by 6% (HR 0.81: 60 vs 66%), and 5-year disease-free survival
      rate by 8%, though there is still considerable need for improvement as most patients who
      relapse are incurable. The unmet need is particularly higher in patients that are at high
      risk of recurrence. The main negative prognostic factors are higher FIGO stage as well as the
      presence of positive lymph nodes. Current studies are evaluating role of adjuvant
      chemotherapy following chemo-radiation in locally advanced disease and will possibly improve
      survival by reducing risk of distant metastases, however at the cost of excessive toxicity.

      PARP inhibitors have shown considerable clinical benefit especially in platinum-sensitive
      relapsed ovarian cancer. Several PARP inhibitors have been evaluated in other gynaecological
      malignancies and three PARP inhibitors (olaparib, rucaparib & niraparib) are approved by
      European Medicines Agency and Food & Drug Administration for treatment or as maintenance
      therapy in ovarian cancer. Human papillomavirus causes oxidative stress that may result in
      DNA single-strand breaks. In cervical cancer PARP-1 expression/activity may be up-regulated
      in response to the ongoing oxidative stress (HPV and inflammation), and this may promote
      progression. This may create a vicious circle of inflammation, PARP activation, NAD+
      consumption, adenosine triphosphate consumption, necrosis, and inflammation. PARPi may limit
      the role of PARP-1 in promoting inflammation and oxidative stress. There is theoretical
      plausibility that PARPi may have a role in the treatment of cervical carcinoma.

      This phase II randomized placebo-controlled double-blind study will evaluate the efficacy and
      safety of rucaparib as adjuvant treatment for patients with locally advanced cervical cancer
      who are responding to chemo-radiation. This investigator-initiated study will be performed
      within the GCIG/ENGOT collaboration
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a multicentre, phase 2, double-blind, placebo-controlled trial of maintenance rucaparib to obtain evidence of clinical benefit of rucaparib in locally advanced cervical cancer.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: double-blinded placebo-controlled
measure: Progression-Free Survival in months
time frame: 42 months
description: the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first.
measure: Progression Free Survival in Sub-Population in months
time frame: 42 months
description: the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first for the predefined study subgroups.
measure: Patient Reported Outcomes
time frame: 42 months
description: Quality of Life Questionnaire
measure: Overall Survival in months
time frame: 60 months
description: the time from randomization until the date of death by any cause
arm group label: Rucaparib
arm group type: Experimental
description: Patients will be treated with active oral drug, Rucaparib twice daily for 24 months
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients will be treated with oral placebo twice daily for 24 months
intervention type: Drug
intervention name: Rucaparib
description: 2:1 randomization to receive rucaparib/placebo twice daily for 24 month
arm group label: Rucaparib
other name: active maintenance
intervention type: Drug
intervention name: Placebo
description: placebo
arm group label: Placebo
other name: matched placebo maintenance
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms
mesh term: Rucaparib
sharing ipd: Undecided