xml: <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/NCT05977322</url>
    </required_header>
    <id_info>
      <org_study_id>CAAA604A12101</org_study_id>
      <secondary_id>2002-502367-37-00</secondary_id>
      <nct_id>NCT05977322</nct_id>
    </id_info>
    <brief_title>A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors.</brief_title>
    <official_title>A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry and Preliminary Activity of [177Lu]Lu-FF58 in Patients With Selected Advanced Solid Tumors.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Novartis Pharmaceuticals</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Novartis</source>
    <oversight_info>
      <has_dmc>No</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>
        The purpose of the study is to test the safety and dosing of [177Lu]Lu-FF58, a radioligand&#xD;
        therapy for patients with advanced or metastatic tumors that express proteins known as&#xD;
        integrins: alpha-v beta-3 integrin (αvβ3) and alpha-v beta-5 integrin (αvβ5). The study will&#xD;
        also further characterize the radioligand imaging agent [68Ga]Ga-FF58 including its ability&#xD;
        to identify tumor lesions and its safety profile.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study will be done in two parts. The first part is called &quot;escalation&quot; and the second&#xD;
        part is called &quot;expansion&quot;. In both parts of the study, patients will be screened with a&#xD;
        [68Ga]Ga-FF58 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic&#xD;
        resonance imaging (MRI) scan to assess eligibility for treatment with [177Lu]Lu-FF58. In the&#xD;
        escalation part, different doses of [177Lu]Lu-FF58 will be tested to identify the recommended&#xD;
        dose. The expansion part of the study will examine the safety and preliminary efficacy of&#xD;
        [177Lu]Lu-FF58 at the recommended dose determined during the escalation part. The end of&#xD;
        study will occur when at least 80% of the patients in the expansion part have completed the&#xD;
        follow-up for disease progression or discontinued from the study for any reason, and all&#xD;
        patients have completed treatment and the 36 month long term follow- up period, or the study&#xD;
        is terminated early in which case all patients would also be followed up for safety.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2, 2023</start_date>
    <completion_date type="Anticipated">July 15, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 14, 2026</primary_completion_date>
    <phase>Phase 1</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>Incidence and severity of dose limiting toxicities of 177Lu-FF58</measure>
      <time_frame>From start of study treatment until 6 weeks after</time_frame>
      <description>A dose limiting toxicity (DLT) is defined as any AE or abnormal laboratory value of CTCAE (v5.0) Grade 3 or higher that occurs within the DLT evaluation period (i.e., 6 weeks starting from the first administration of 177Lu-FF58) and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence and severity of adverse events and serious adverse events of 177Lu-FF58</measure>
      <time_frame>From start of study treatment until 180 days after the last dose of study treatment, assessed up to approximately 15 months</time_frame>
      <description>The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose modifications for 177Lu-FF58</measure>
      <time_frame>From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks</time_frame>
      <description>Dose modifications (dose interruptions and reductions) for 177Lu-FF58 will be assessed and summarized using descriptive statistics. The number of patients with dose modification and the reasons will be summarized by treatment groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose intensity for 177Lu-FF58</measure>
      <time_frame>From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks</time_frame>
      <description>Dose intensity for 177Lu-FF58 will be assessed and summarized using descriptive statistics. Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall response rate (ORR)</measure>
      <time_frame>From start of study treatment until date of progression, assessed up to approximately 34 months</time_frame>
      <description>ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI using FAS.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR)</measure>
      <time_frame>From start of study treatment until date of progression, assessed up to approximately 34 months</time_frame>
      <description>DOR is the time between the first documented response (CR or PR) and the date of progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause. Here, death due to any cause is considered as an event to be conservative and align with PFS event definition. DOR may be presented graphically if enough events are available for analysis, using Kaplan Meier plots for all patients who achieved a CR/PR in the study. The median DOR and corresponding 90% CI will be presented. Analysis will include responders with confirmed responses.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>From start of study treatment until date of progression, assessed up to approximately 34 months</time_frame>
      <description>DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI, using FAS.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression free survival (PFS)</measure>
      <time_frame>From start of study treatment until date of progression, assessed up to approximately 34 months</time_frame>
      <description>PFS is defined as the time from the date of start of treatment to the date of the first documented progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area Under the Curve (AUC) from 177Lu-FF58 blood radioactivity data</measure>
      <time_frame>Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.</time_frame>
      <description>Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUC from time zero to specified time point (mass x time x volume-1) will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total body clearance from 177Lu-FF58 blood radioactivity data</measure>
      <time_frame>Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.</time_frame>
      <description>Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The total body clearance of drug from the plasma (volume x time-1) will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Observed maximum plasma concentration (Cmax) from 177Lu-FF58 blood radioactivity data</measure>
      <time_frame>Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.</time_frame>
      <description>Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Cmax will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Volume of distribution during the terminal phase following intravenous elimination (Vz) from 177Lu-FF58 blood radioactivity data</measure>
      <time_frame>Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.</time_frame>
      <description>Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Vz will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Terminal elimination half-life (T^1/2) from 177Lu-FF58 blood radioactivity data</measure>
      <time_frame>Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.</time_frame>
      <description>Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The half-life will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA)</measure>
      <time_frame>Cycle 1: Pre-infusion,beginning of infusion to first SPECT/CT image acquisition,first SPECT/CT image acquisition and 6 hours(hr) post-end-of infusion(EOI),6-24hr post-EOI,24-48hr post-EOI,48-72hr post-EOI. Cycle= 6 weeks or 3 weeks depending on schedule.</time_frame>
      <description>Urine samples will be collected over specified time intervals and analysed for radioactivity. The radioactivity excreted in each interval as a percentage of injected activity (%IA) will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time-activity curves (TACs) related to 177Lu-FF58 uptake in organs and tumor lesions</measure>
      <time_frame>Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.</time_frame>
      <description>Time-activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%IA/g) as a function of time.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Absorbed dose of 177Lu-FF58</measure>
      <time_frame>Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.</time_frame>
      <description>The absorbed dose in target organs will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity of adverse events and serious adverse events of 68Ga-FF58</measure>
      <time_frame>From Imaging visit until 14 days after 68Ga-FF58 administration, or until first dose of study treatment</time_frame>
      <description>The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Imaging properties: Visual and quantitative assessment (expressed as SUV) and tumor-to-background ratio (TBR) of 68Ga-FF58 uptake in organs and tumor lesions over time</measure>
      <time_frame>From Imaging until 1 hour (hr), 2 hr and 3 hr after 68Ga-FF58 administration</time_frame>
      <description>After 68Ga-FF58 administration, 68Ga-FF58 PET/CT or PET/MRI will be performed. The statistical analyses of imaging properties of 68Ga-FF58 will be descriptive in nature and will include summaries and graphical presentations of data. No formal testing will be performed.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">116</enrollment>
    <condition>Pancreatic Ductal Adenocarcinoma</condition>
    <condition>Gastroesophageal Adenocarcinoma</condition>
    <condition>Glioblastoma Multiforme</condition>
    <arm_group>
      <arm_group_label>Arm 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will receive 68Ga-FF58 and only patients with tumor uptake of 68Ga-FF58 will receive 177Lu-FF58.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>68Ga-FF58</intervention_name>
      <description>Kit for radiopharmaceutical preparation of 68Ga- FF58 solution for injection</description>
      <arm_group_label>Arm 1</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>177Lu-FF58</intervention_name>
      <description>Solution for injection/infusion</description>
      <arm_group_label>Arm 1</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion criteria&#xD;
  &#xD;
            -  Age &gt;= 18 years old&#xD;
  &#xD;
            -  Patients with locally advanced unresectable or metastatic PDAC, locally advanced&#xD;
               unresectable or metastatic GEA, or recurrent GBM&#xD;
  &#xD;
            -  To be treated with [177Lu]Lu-FF58, patients must have at least one measurable lesion&#xD;
               that shows [68Ga]Ga-FF58 uptake on PET/CT or PET/MRI&#xD;
  &#xD;
          Key Exclusion criteria&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) &lt; 1.5 x 109/L, hemoglobin &lt; 10 g/dL, or platelet count&#xD;
               &lt; 100 x 109/L&#xD;
  &#xD;
            -  Prior external beam radiation therapy (EBRT) to &gt; 25% of the bone marrow&#xD;
  &#xD;
            -  Creatinine clearance &lt; 60 mL/min&#xD;
  &#xD;
            -  Unmanageable bladder outflow obstruction or urinary incontinence&#xD;
  &#xD;
            -  Non-GBM patients: Presence of symptomatic central nervous system (CNS) metastases, or&#xD;
               CNS metastases that require local CNS-directed therapy (such as radiotherapy or&#xD;
               surgery), or increasing doses of corticosteroids within 1 week before [177Lu]Lu-FF58&#xD;
               administration&#xD;
  &#xD;
          Other protocol-defined inclusion/exclusion criteria may apply&#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>Novartis Pharmaceuticals</last_name>
      <role>Study Director</role>
      <affiliation>Novartis Pharmaceuticals</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Novartis Pharmaceuticals</last_name>
      <phone>1-888-669-6682</phone>
      <email>novartis.email@novartis.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Novartis Pharmaceuticals</last_name>
      <phone>+41613241111</phone>
      <email>novartis.email@novartis.com</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 10, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 28, 2023</last_update_submitted>
    <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>pancreatic ductal adenocarcinoma</keyword>
    <keyword>PDAC</keyword>
    <keyword>pancreatic cancer</keyword>
    <keyword>gastroesophageal adenocarcinoma</keyword>
    <keyword>GEA</keyword>
    <keyword>gastric cancer</keyword>
    <keyword>gastric adenocarcinoma</keyword>
    <keyword>esophageal cancer</keyword>
    <keyword>esophageal adenocarcinoma</keyword>
    <keyword>glioblastoma multiforme</keyword>
    <keyword>GBM</keyword>
    <keyword>advanced solid tumors</keyword>
    <keyword>radioligand therapy</keyword>
    <keyword>RLT</keyword>
    <keyword>[177Lu]Lu-FF58</keyword>
    <keyword>[68Ga]Ga-FF58</keyword>
    <keyword>integrins</keyword>
    <keyword>alpha-v beta-3 integrin</keyword>
    <keyword>αvβ3</keyword>
    <keyword>alpha-v beta-5 integrin</keyword>
    <keyword>αvβ5</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Adenocarcinoma</mesh_term>
      <mesh_term>Glioblastoma</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05977322
  org study id: CAAA604A12101
  secondary id: 2002-502367-37-00
  nct id: NCT05977322
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of the study is to test the safety and dosing of [177Lu]Lu-FF58, a radioligand
        therapy for patients with advanced or metastatic tumors that express proteins known as
        integrins: alpha-v beta-3 integrin (αvβ3) and alpha-v beta-5 integrin (αvβ5). The study will
        also further characterize the radioligand imaging agent [68Ga]Ga-FF58 including its ability
        to identify tumor lesions and its safety profile.
  The study will be done in two parts. The first part is called "escalation" and the second
        part is called "expansion". In both parts of the study, patients will be screened with a
        [68Ga]Ga-FF58 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic
        resonance imaging (MRI) scan to assess eligibility for treatment with [177Lu]Lu-FF58. In the
        escalation part, different doses of [177Lu]Lu-FF58 will be tested to identify the recommended
        dose. The expansion part of the study will examine the safety and preliminary efficacy of
        [177Lu]Lu-FF58 at the recommended dose determined during the escalation part. The end of
        study will occur when at least 80% of the patients in the expansion part have completed the
        follow-up for disease progression or discontinued from the study for any reason, and all
        patients have completed treatment and the 36 month long term follow- up period, or the study
        is terminated early in which case all patients would also be followed up for safety.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence and severity of dose limiting toxicities of 177Lu-FF58
  time frame: From start of study treatment until 6 weeks after
  description: A dose limiting toxicity (DLT) is defined as any AE or abnormal laboratory value of CTCAE (v5.0) Grade 3 or higher that occurs within the DLT evaluation period (i.e., 6 weeks starting from the first administration of 177Lu-FF58) and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications.
  measure: Incidence and severity of adverse events and serious adverse events of 177Lu-FF58
  time frame: From start of study treatment until 180 days after the last dose of study treatment, assessed up to approximately 15 months
  description: The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
  measure: Dose modifications for 177Lu-FF58
  time frame: From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks
  description: Dose modifications (dose interruptions and reductions) for 177Lu-FF58 will be assessed and summarized using descriptive statistics. The number of patients with dose modification and the reasons will be summarized by treatment groups.
  measure: Dose intensity for 177Lu-FF58
  time frame: From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks
  description: Dose intensity for 177Lu-FF58 will be assessed and summarized using descriptive statistics. Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure.
  measure: Overall response rate (ORR)
  time frame: From start of study treatment until date of progression, assessed up to approximately 34 months
  description: ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI using FAS.
  measure: Duration of Response (DOR)
  time frame: From start of study treatment until date of progression, assessed up to approximately 34 months
  description: DOR is the time between the first documented response (CR or PR) and the date of progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause. Here, death due to any cause is considered as an event to be conservative and align with PFS event definition. DOR may be presented graphically if enough events are available for analysis, using Kaplan Meier plots for all patients who achieved a CR/PR in the study. The median DOR and corresponding 90% CI will be presented. Analysis will include responders with confirmed responses.
  measure: Disease control rate (DCR)
  time frame: From start of study treatment until date of progression, assessed up to approximately 34 months
  description: DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI, using FAS.
  measure: Progression free survival (PFS)
  time frame: From start of study treatment until date of progression, assessed up to approximately 34 months
  description: PFS is defined as the time from the date of start of treatment to the date of the first documented progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause.
  measure: Area Under the Curve (AUC) from 177Lu-FF58 blood radioactivity data
  time frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.
  description: Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUC from time zero to specified time point (mass x time x volume-1) will be listed and summarized using descriptive statistics.
  measure: Total body clearance from 177Lu-FF58 blood radioactivity data
  time frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.
  description: Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The total body clearance of drug from the plasma (volume x time-1) will be listed and summarized using descriptive statistics.
  measure: Observed maximum plasma concentration (Cmax) from 177Lu-FF58 blood radioactivity data
  time frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.
  description: Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Cmax will be listed and summarized using descriptive statistics.
  measure: Volume of distribution during the terminal phase following intravenous elimination (Vz) from 177Lu-FF58 blood radioactivity data
  time frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.
  description: Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Vz will be listed and summarized using descriptive statistics.
  measure: Terminal elimination half-life (T^1/2) from 177Lu-FF58 blood radioactivity data
  time frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.
  description: Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The half-life will be listed and summarized using descriptive statistics.
  measure: Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA)
  time frame: Cycle 1: Pre-infusion,beginning of infusion to first SPECT/CT image acquisition,first SPECT/CT image acquisition and 6 hours(hr) post-end-of infusion(EOI),6-24hr post-EOI,24-48hr post-EOI,48-72hr post-EOI. Cycle= 6 weeks or 3 weeks depending on schedule.
  description: Urine samples will be collected over specified time intervals and analysed for radioactivity. The radioactivity excreted in each interval as a percentage of injected activity (%IA) will be listed and summarized using descriptive statistics.
  measure: Time-activity curves (TACs) related to 177Lu-FF58 uptake in organs and tumor lesions
  time frame: Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.
  description: Time-activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%IA/g) as a function of time.
  measure: Absorbed dose of 177Lu-FF58
  time frame: Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.
  description: The absorbed dose in target organs will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.
  measure: Incidence and severity of adverse events and serious adverse events of 68Ga-FF58
  time frame: From Imaging visit until 14 days after 68Ga-FF58 administration, or until first dose of study treatment
  description: The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
  measure: Imaging properties: Visual and quantitative assessment (expressed as SUV) and tumor-to-background ratio (TBR) of 68Ga-FF58 uptake in organs and tumor lesions over time
  time frame: From Imaging until 1 hour (hr), 2 hr and 3 hr after 68Ga-FF58 administration
  description: After 68Ga-FF58 administration, 68Ga-FF58 PET/CT or PET/MRI will be performed. The statistical analyses of imaging properties of 68Ga-FF58 will be descriptive in nature and will include summaries and graphical presentations of data. No formal testing will be performed.
  arm group label: Arm 1
  arm group type: Experimental
  description: Patients will receive 68Ga-FF58 and only patients with tumor uptake of 68Ga-FF58 will receive 177Lu-FF58.
  intervention type: Drug
  intervention name: 68Ga-FF58
  description: Kit for radiopharmaceutical preparation of 68Ga- FF58 solution for injection
  arm group label: Arm 1
  intervention type: Drug
  intervention name: 177Lu-FF58
  description: Solution for injection/infusion
  arm group label: Arm 1
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Novartis Pharmaceuticals
  role: Study Director
  affiliation: Novartis Pharmaceuticals
  last name: Novartis Pharmaceuticals
  phone: 1-888-669-6682
  email: novartis.email@novartis.com
  last name: Novartis Pharmaceuticals
  phone: +41613241111
  email: novartis.email@novartis.com
  responsible party type: Sponsor
  mesh term: Adenocarcinoma
  mesh term: Glioblastoma
  sharing ipd: No