89Zr-girentuximab for PET Imaging of CAIX Positive Solid Tumors

Study Overview
=================
Brief Summary
-----------------
A prospective, open-label, phase 2 study to explore CAIX expression through 89Zirconium-labelled girentuximab deferoxamine (89Zr-girentuximab) PET/CT imaging in patients with solid tumors.

Official Title
-----------------
Study of 89Zr-girentuximab for PET Imaging of Solid Tumors Likely to Express High Levels of CAIX

Conditions
-----------------
Cervical Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer, Glioblastoma Multiforme, Cholangiocarcinoma, Hepatocellular Carcinoma, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal Carcinoma, Non Small Cell Lung Cancer, Small Cell Lung Cancer, Epithelial Ovarian Cancer, Pancreatic Ductal Adenocarcinoma, Soft Tissue Sarcoma

Intervention / Treatment
-----------------
* Drug: 89Zr-DFO-girentuximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written and voluntarily given Informed Consent. Male or female ≥18 years of age at time of consent. Have the capacity to understand the study and be willing and able to comply with all protocol requirements. Participants must have histologically or cytologically proven solid tumors of the following types, but not limited to: cervical cancer colorectal cancer esophageal cancer (esophageal SCC and esophageal/esophagogastric junction adenocarcinoma) gastric cancer (gastric adenocarcinoma) glioblastoma multiforme head and neck cancer (head and neck SCC and nasopharyngeal carcinoma) liver cancer (cholangiocarcinoma and hepatocellular carcinoma) lung cancer (non-smallcell and small cell) ovarian cancer (epithelial ovarian carcinoma) pancreatic cancer (pancreatic ductal adenocarcinoma) soft tissue sarcoma At least one non-CNS, measurable target lesion as per RECIST 1.1 documented at conventional imaging, performed within 30 days prior to Day 0. Participant agrees not to participate in another interventional study while participating in the present study, defined as signing the informed consent form (ICF) until completion of the last study visit. Negative serum pregnancy tests in female patients of childbearing potential at screening and confirmation of negative pregnancy test result from urine within24 hours prior to receiving investigational product. Female patients of non-child-bearing potential must provide evidence by fulfilling one of the following criteria at screening: Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizinghormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation For all participants, consent to practice double-barrier contraception until a minimum of 42 days after 89Zr-girentuximab administration. Exclusion Criteria: Exposure to murine or chimeric antibodies within the last 5 years. Previous administration of any radionuclide within 10 half-lives (of the radionuclide) prior to the intended administration of 89Zr-girentuximab(i.e., within 10 half-lives of Day0). Exposure to any CAIX targeting compound (diagnostic/therapeutic) in the last 3 months Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic) that may interfere with the objectives of the study or with the safety or compliance of the subject, as judged by the Investigator. Any clinically significant abnormalities detected during screening laboratory tests or physical exam that in the opinion of the Investigator would adversely affect the participants ability to participate in the study. Principal Investigator to assess patient suitability for inclusion based on pathology and tumor type. Mental impairment that may compromise the ability to give Informed Consent and comply with the requirements of the study. Exposure to any antineoplastic treatment within 14 days from the date of planned administration of 89Zr-girentuximab(i.e. within 14 days of Day 0). Women who are pregnant or breastfeeding. Known allergy, hypersensitivity, or intolerance to girentuximab, DFO (desferrioxamine),or any of the components of the investigationalagent.10.Renal insufficiency with glomerular filtration rate (GFR) ≤ 45 millilitres/min/1.73m2 Vulnerable patients (e.g. being in detention).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 89Zr-DFO-girentuximab|Single IV administration on Day 0, followed by diagnostic scan on Day 5 +/- 2 days.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative assessment of 89Zr-girentuximab uptake within individual tumor deposits | This outcome will be evaluated on all patients by using a PET/CT machine to qualitatively assess (yes / no) the uptake of the 89Zr-girentuximab uptake within individual tumor deposits. | Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. This assessment will be conducted throughout the patient dosing and imaging period, an average of 18 months | 
| Quantitative assessment of 89Zr-girentuximab uptake within individual tumor deposits | This outcome will be evaluated on all patients by using a PET/CT machine to quantitatively assess the uptake of the 89Zr-girentuximab uptake within individual tumor deposits. | Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. This assessment will be conducted throughout the patient dosing and imaging period, an average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety parameter of Heart rate in patients administered with 89Zr-girentuximab | This outcome will be measured as beats per minute on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria | Patients will be evaluated for the period up to imaging following administration of 89Zr-girentuximab, at most 7 days. | 
| To evaluate safety parameter of blood pressure in patients administered with 89Zr-girentuximab. | This outcome will be measured as mmHg on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria | Patients will be evaluated for the period up to imaging following administration of 89Zr-girentuximab, up to 7 days. | 
| To evaluate safety parameter related to Liver function in patients administered 89Zr-girentuximab | This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values. | Patients will be evaluated for the period up to imaging following administration of 89Zr-girentuximab, up to 7 days. | 
| To evaluate safety parameter related to Renal function in patients administered 89Zr-girentuximab | This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values. | Patients will be evaluated for the period up to imaging following administration of 89Zr-girentuximab, up to 7 days. | 
| To evaluate safety parameter related to Full Blood Count in patients administered 89Zr-girentuximab | This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values. | Patients will be evaluated for the period up to imaging following administration of 89Zr-girentuximab, up to 7 days. |