<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/NCT03283605</url>
  </required_header>
  <id_info>
    <org_study_id>ESR-16-12361</org_study_id>
    <nct_id>NCT03283605</nct_id>
  </id_info>
  <brief_title>Immunotherapy and SBRT for Metastatic Head and Neck Carcinomas</brief_title>
  <official_title>Phase I/II of Durvalumab (MEDI4736) + Tremelimumab + Stereotactic Body Radiotherapy for Metastatic Head and Neck Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre hospitalier de l'Université de Montréal (CHUM)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre hospitalier de l'Université de Montréal (CHUM)</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>
      Immunotherapy targeting the PD-1/PD-L1 pathway had previously been shown to be efficacious in&#xD;
      the treatment of patients with metastatic head and neck squamous cell carcinomas.&#xD;
      Stereotactic Body Radiotherapy (SBRT) to metastatic lesions causes localized cancer cell&#xD;
      killing and the release of cancer cell debris, which could stimulate the immune system in the&#xD;
      presence of immunotherapy. The purpose of this study is to assess the tolerability and&#xD;
      efficacy of combining Durvalumab (MEDI4736), Tremelimumab and SBRT in controlling cancer&#xD;
      progression. SBRT will be administered to patients while they are receiving Durvalumab and&#xD;
      Tremelimumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 17, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 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>Single Group Assignment</intervention_model>
    <intervention_model_description>Single group assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open-label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Acute toxicities of the treatment</measure>
    <time_frame>3 months</time_frame>
    <description>The rate of Grade 3-5 combination TTC-related toxicities within 12 weeks from the start of SBRT treatments. The results will be tabulated to examine their frequency, organ systems affected, severity, and relationship to study treatment.&#xD;
Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs. Investigators will provide their assessment of causality as 1) unrelated, 2) unlikely, 3) possibly related, 4) probably, or 5) definitely related.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>6 months</time_frame>
    <description>To evaluate whether the combination SBRT with Durvalumab and Tremelimumab will improve the progression-free survival of patients.&#xD;
Response will be assessed as per RECIST version 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local control (LC)</measure>
    <time_frame>2 years</time_frame>
    <description>Defined as stable disease, partial response, or complete response based on serial imaging with CT scan. Recurrence will be defined as a suspicious mass at the site of SBRT treated lesion, progressing in size on 2 consecutive computed tomography scans at a minimum interval of 1 month, combined with a positive FDG-PET defined by a SUV max ≥ 5, or a biopsy-proven confirmation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>2 years</time_frame>
    <description>Regional or distant disease progression according to RECIST v1.1 or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>2 years</time_frame>
    <description>A subject will be classified as either alive or dead due to any cause. The time to event will be calculated as the time from Day 1 until date of death. Day 1 is the date of 1st treatment with durvalumab and tremelimumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abscopal events</measure>
    <time_frame>2 years</time_frame>
    <description>Defined as anti-tumor response outside the radiotherapy field.&#xD;
Response will be assessed as per RECIST version 1.1.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Metastatic Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Durvalumab + tremelimumab and SBRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will receive durvalumab (1500 mg IV q4week) and tremelimumab (75mg q4week) for 4 doses, followed by durvalumab alone (1500 mg IV q4week) until disease progression, unacceptable toxicity or patient withdrawal. SBRT will be administered between cycle 2 and 3 of durvalumab and tremelimumab. All SBRT will be completed within a 3-week period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SBRT</intervention_name>
    <description>SBRT to 2-5 oligometastases will be administered between Cycle 2 and 3 of durvalumab and tremelimumab. All SBRT will be completed within a 3-week period.</description>
    <arm_group_label>Durvalumab + tremelimumab and SBRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab (1500 mg IV q4weeks) for 4 cycles in combination with tremelimumab. Then, durvalumab alone until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria met.</description>
    <arm_group_label>Durvalumab + tremelimumab and SBRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tremelimumab</intervention_name>
    <description>Tremelimumab (75mg IV q4weeks) for 4 cycles in combination with Durvalumab.</description>
    <arm_group_label>Durvalumab + tremelimumab and SBRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pathologically (histologically or cytologically) confirmed diagnosis HNSCC at a&#xD;
             metastatic site. This includes histologic variants of SCC such as spindle cell&#xD;
             carcinoma, poorly differentiated keratin-positive carcinoma, and lymphoepithelioma.&#xD;
             The pathology can come from the most accessible site and does not need to be from the&#xD;
             time of diagnosis.&#xD;
&#xD;
          2. ≥2 locoregional and/or extracranial metastatic lesions (no brain metastases) that are&#xD;
             treatable by SBRT. Lesions that are not measurable per RECIST v1.1 must show&#xD;
             progression on 2 consecutive imaging studies with a minimum increase of 1 mm, and must&#xD;
             be a mimimum size of 5 mm at time of enrollment. .&#xD;
&#xD;
          3. ≤ 4 prior treatment lines with systemic therapy&#xD;
&#xD;
          4. ≥2 measurable disease (RECIST) consisting of extracranial metastatic lesions (no brain&#xD;
             metastasis) that are treatable by SBRT.&#xD;
&#xD;
          5. ≤ 10 metastatic lesions&#xD;
&#xD;
          6. Life expectancy &gt; 24 weeks&#xD;
&#xD;
          7. Evaluation by a radiation oncologist within 45 days prior to study registration&#xD;
&#xD;
          8. Evaluation by a medical oncologist within 45 days prior to study registration&#xD;
&#xD;
          9. Body weight &gt;30kg&#xD;
&#xD;
         10. The following imaging workup to document metastases within 45 days prior to study&#xD;
             registration:&#xD;
&#xD;
               -  CT scans of the chest, abdomen and pelvis OR whole body PET/CT&#xD;
&#xD;
         11. ≥ 18 years of age at time of study entry&#xD;
&#xD;
         12. Up to 4 prior treatment lines with systemic therapy are allowed&#xD;
&#xD;
         13. Eastern Cooperative Oncology Group/World Health Organisation (ECOG/WHO) performance&#xD;
             status score of ≤ 1&#xD;
&#xD;
         14. Patients with locoregional recurrence(s) can be included only if they have evidence of&#xD;
             distant metastasis; patients with locoregional recurrences which are symptomatic&#xD;
             and/or potentially affect quality of life may undergo palliative radiation therapy to&#xD;
             this region prior to enrollment on the protocol at the discretion of the treating&#xD;
             physician. However, a minimum of 6 weeks must elapse before receiving protocol&#xD;
             treatment.&#xD;
&#xD;
         15. Adequate normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Haemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count (ANC ≥ 1.5 (or 1.0) x (&gt; 1500 per mm3)&#xD;
&#xD;
               -  Platelet count ≥ 100 (or 75) x 109/L (&gt;75,000 per mm3)&#xD;
&#xD;
               -  Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not&#xD;
                  apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent&#xD;
                  hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis&#xD;
                  or hepatic pathology), who will be allowed only in consultation with their&#xD;
                  physician.&#xD;
&#xD;
               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver&#xD;
                  metastases are present, in which case it must be ≤ 5x ULN&#xD;
&#xD;
               -  Serum creatinine CL&gt;40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault&#xD;
                  1976) or by 24-hour urine collection for determination of creatinine clearance&#xD;
                  (calculated by study site staff)&#xD;
&#xD;
         16. Evidence of post-menopausal status or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients. Women will be considered post-menopausal if they have&#xD;
             been amenorrheic for 12 months without an alternative medical cause. The following&#xD;
             age-specific requirements apply:&#xD;
&#xD;
               -  Women &lt;50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone&#xD;
                  levels in the post-menopausal range for the institution or underwent surgical&#xD;
                  sterilization (bilateral oophorectomy or hysterectomy).&#xD;
&#xD;
               -  Women ≥50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal&#xD;
                  treatments, had radiation-induced menopause with last menses &gt;1 year ago, had&#xD;
                  chemotherapy-induced menopause with last menses &gt;1 year ago, or underwent&#xD;
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or&#xD;
                  hysterectomy).&#xD;
&#xD;
         17. Patient is willing and able to give written informed consent, prior to performing any&#xD;
             protocol-related procedures, including screening evaluations.&#xD;
&#xD;
         18. Patient is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations including follow&#xD;
             up.&#xD;
&#xD;
         19. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4, including&#xD;
             durvalumab and tremelimumab if the following are fulfilled:&#xD;
&#xD;
               -  Must not have experienced a toxicity that led to permanent discontinuation of&#xD;
                  prior immunotherapy.&#xD;
&#xD;
               -  All AEs of prior immunotherapy must have completely resolved or resolved to&#xD;
                  baseline prior to screening for this study.&#xD;
&#xD;
               -  Must not have experienced a ≥ Grade 3 immune related AE or an immune related&#xD;
                  neurologic or ocular AE of any grade while receiving prior immunotherapy.&#xD;
&#xD;
               -  Must not have required the use of additional immunosuppression other than&#xD;
                  corticosteroids for the management of an AE and not have experienced recurrence&#xD;
                  of an AE if re-challenged.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             staff and/or staff at the study site)&#xD;
&#xD;
          2. Nasopharyngeal carcinoma&#xD;
&#xD;
          3. Concurrent enrolment in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study or during the follow-up period of an&#xD;
             interventional study.&#xD;
&#xD;
          4. &gt;4 prior treatment lines with systemic therapy&#xD;
&#xD;
          5. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,&#xD;
             endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal&#xD;
             antibodies) ≤ 30 days prior to the first dose of study drug. If sufficient wash-out&#xD;
             time has not occurred due to the schedule or PK properties of an agent, a longer&#xD;
             wash-out period will be required, as agreed by AstraZeneca/MedImmune and the&#xD;
             investigator.&#xD;
&#xD;
          6. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the&#xD;
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion&#xD;
             criteria&#xD;
&#xD;
               -  Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after&#xD;
                  consultation with the Study Physician.&#xD;
&#xD;
               -  Patients with irreversible toxicity not reasonably expected to be exacerbated by&#xD;
                  treatment with durvalumab or tremelimumab may be included only after consultation&#xD;
                  with the Study Physician.&#xD;
&#xD;
          7. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.&#xD;
             Concurrent use of hormonal therapy for non-cancer-related conditions (eg. hormone&#xD;
             replacement therapy) is acceptable.&#xD;
&#xD;
          8. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of&#xD;
             radiation within 4 weeks of the first dose of study drug&#xD;
&#xD;
          9. Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of IP. Note: Local surgery of isolated lesions for palliative intent is&#xD;
             acceptable.&#xD;
&#xD;
         10. History of allogenic organ transplantation.&#xD;
&#xD;
         11. Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the&#xD;
             exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or&#xD;
             Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid&#xD;
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this&#xD;
             criterion:&#xD;
&#xD;
               -  Patients with vitiligo or alopecia&#xD;
&#xD;
               -  Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone&#xD;
                  replacement&#xD;
&#xD;
               -  Any chronic skin condition that does not require systemic therapy&#xD;
&#xD;
               -  Patients without active disease in the last 5 years may be included but only&#xD;
                  after consultation with the study physician&#xD;
&#xD;
               -  Patients with celiac disease controlled by diet alone&#xD;
&#xD;
         12. Uncontrolled undercurrent illness, including but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic&#xD;
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirement, substantially increase&#xD;
             risk of incurring AEs or compromise the ability of the patient to give written&#xD;
             informed consent&#xD;
&#xD;
         13. History of another primary malignancy except for&#xD;
&#xD;
               -  Malignancy treated with curative intent and with no known active disease ≥5 years&#xD;
                  before the first dose of IP and of low potential risk for recurrence&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease&#xD;
&#xD;
               -  Adequately treated carcinoma in situ without evidence of disease&#xD;
&#xD;
         14. History of leptomeningeal carcinomatosis&#xD;
&#xD;
         15. Brain metastases or spinal cord compression. Patients with suspected brain metastases&#xD;
             at screening should have an MRI (preferred) or CT each preferably with IV contrast of&#xD;
             the brain prior to study entry.&#xD;
&#xD;
         16. Current or prior use of immunosuppressive medication within 14 days before the first&#xD;
             dose of durvalumab or tremelimumab. The following are exceptions to this criterion:&#xD;
&#xD;
               -  Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra&#xD;
                  articular injection)&#xD;
&#xD;
               -  Systemic corticosteroids at physiologic doses not to exceed &lt;&lt;10 mg/day&gt;&gt; of&#xD;
                  prednisone or its equivalent&#xD;
&#xD;
               -  Steroids as premedication for hypersensitivity reactions (eg, CT scan&#xD;
                  premedication)&#xD;
&#xD;
         17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:&#xD;
             Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to&#xD;
             30 days after the last dose of IP.&#xD;
&#xD;
         18. Female patients who are pregnant or breastfeeding or male or female patients of&#xD;
             reproductive potential who are not willing to employ effective birth control from&#xD;
             screening to 90 days after the last dose of durvalumab monotherapy or180 days after&#xD;
             the last dose of durvalumab + tremelimumab combination therapy.&#xD;
&#xD;
         19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
             excipients.&#xD;
&#xD;
         20. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required&#xD;
             steroid treatment, or any evidence of clinically active interstitial lung disease.&#xD;
&#xD;
         21. Judgment by the investigator that the patient is unsuitable to participate in the&#xD;
             study and the patient is unlikely to comply with study procedures, restrictions and&#xD;
             requirements.&#xD;
&#xD;
         22. Female patients who are pregnant or breastfeeding or male or female patients of&#xD;
             reproductive potential who are not willing to employ effective birth control from&#xD;
             screening to 180 days after the last dose of durvalumab + tremelimumab combination&#xD;
             therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the&#xD;
             longer time period.&#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>Cross Cancer Institute</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Regional Cancer Program of the Lawson Health Research Institute</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Université de Montréal</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2L 4M1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>November 11, 2022</last_update_submitted>
  <last_update_submitted_qc>November 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</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/NCT03283605
org study id: ESR-16-12361
nct id: NCT03283605
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Immunotherapy targeting the PD-1/PD-L1 pathway had previously been shown to be efficacious in
      the treatment of patients with metastatic head and neck squamous cell carcinomas.
      Stereotactic Body Radiotherapy (SBRT) to metastatic lesions causes localized cancer cell
      killing and the release of cancer cell debris, which could stimulate the immune system in the
      presence of immunotherapy. The purpose of this study is to assess the tolerability and
      efficacy of combining Durvalumab (MEDI4736), Tremelimumab and SBRT in controlling cancer
      progression. SBRT will be administered to patients while they are receiving Durvalumab and
      Tremelimumab.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single group assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open-label
measure: Acute toxicities of the treatment
time frame: 3 months
description: The rate of Grade 3-5 combination TTC-related toxicities within 12 weeks from the start of SBRT treatments. The results will be tabulated to examine their frequency, organ systems affected, severity, and relationship to study treatment.
Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs. Investigators will provide their assessment of causality as 1) unrelated, 2) unlikely, 3) possibly related, 4) probably, or 5) definitely related.
measure: Progression Free Survival (PFS)
time frame: 6 months
description: To evaluate whether the combination SBRT with Durvalumab and Tremelimumab will improve the progression-free survival of patients.
Response will be assessed as per RECIST version 1.1.
measure: Local control (LC)
time frame: 2 years
description: Defined as stable disease, partial response, or complete response based on serial imaging with CT scan. Recurrence will be defined as a suspicious mass at the site of SBRT treated lesion, progressing in size on 2 consecutive computed tomography scans at a minimum interval of 1 month, combined with a positive FDG-PET defined by a SUV max ≥ 5, or a biopsy-proven confirmation.
measure: Progression-free survival (PFS)
time frame: 2 years
description: Regional or distant disease progression according to RECIST v1.1 or death due to any cause
measure: Overall survival (OS)
time frame: 2 years
description: A subject will be classified as either alive or dead due to any cause. The time to event will be calculated as the time from Day 1 until date of death. Day 1 is the date of 1st treatment with durvalumab and tremelimumab.
measure: Abscopal events
time frame: 2 years
description: Defined as anti-tumor response outside the radiotherapy field.
Response will be assessed as per RECIST version 1.1.
arm group label: Durvalumab + tremelimumab and SBRT
arm group type: Experimental
description: All subjects will receive durvalumab (1500 mg IV q4week) and tremelimumab (75mg q4week) for 4 doses, followed by durvalumab alone (1500 mg IV q4week) until disease progression, unacceptable toxicity or patient withdrawal. SBRT will be administered between cycle 2 and 3 of durvalumab and tremelimumab. All SBRT will be completed within a 3-week period.
intervention type: Radiation
intervention name: SBRT
description: SBRT to 2-5 oligometastases will be administered between Cycle 2 and 3 of durvalumab and tremelimumab. All SBRT will be completed within a 3-week period.
arm group label: Durvalumab + tremelimumab and SBRT
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab (1500 mg IV q4weeks) for 4 cycles in combination with tremelimumab. Then, durvalumab alone until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria met.
arm group label: Durvalumab + tremelimumab and SBRT
intervention type: Drug
intervention name: Tremelimumab
description: Tremelimumab (75mg IV q4weeks) for 4 cycles in combination with Durvalumab.
arm group label: Durvalumab + tremelimumab and SBRT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Durvalumab
mesh term: Tremelimumab