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PET imaging will begin 30 +/-10 minutes, 60 +/-15 minutes and 120 +/-20 minutes after injection of 68Ga-FAP-2286. Contrast may be administered if clinically indicated.

PET imaging will begin 60±15 minutes, 240±30 minutes after injection,and 24±2 hours after injection of 64Cu-FAP-2286. Contrast may be administered if clinically indicated.

Participants with metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if clinically indicated.

Participants without metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if if clinically indicated.

The dose will be 3 to 8 millicurie (mCi) +/- 10% given intravenously at a single time prior to imaging

Gallium-68 labelled (68Ga-) FAP-2286

Participants will be scanned for approximately 30 to 45 minutes

Positron Emission Tomography (PET) imaging

The dose will be 3.5 to 5.5 millicurie (mCi) +/- 10% given intravenously at a single time prior to imaging

Copper-64 labeled (64Cu-) FAP-2286

Maya Aslam

Thomas Hope, MD

This is a multi-arm prospective trial that evaluates the ability of a novel imaging radiolabeled agents to detect metastatic cancer in participants with solid tumors using a gallium 68 (68Ga-) or copper 64 (64Cu-) FAP-2286 tracer. FAP-2286 is a peptidomimetic molecule that that binds to Fibroblast Activation Protein (FAP). FAP is a transmembrane protein expressed on cancer-associated fibroblasts, and has been shown to be present on a number of solid tumors.

Initially the investigator(s) will focus on imaging breast, pancreas, sarcoma, prostate cancer, bladder cancer, colon cancer, and head and neck cancer.

STUDY AIMS

1. Determine the dosimetry for gallium-68 labelled (68Ga-) and 64Cu- FAP-2286.
2. Evaluate the uptake and retention of radiotracer in a variety of solid tumors with FAP-2286.
3. Evaluate the ability of FAP-2286 to detect metastatic disease.

PRIMARY OBJECTIVES

1. All cohorts: Safety of 68Ga- and 64Cu-FAP-2286.
2. Cohort 1a: determine the organ dosimetry of 68Ga-FAP-2286.
3. Cohort 1b: determine the organ dosimetry of 64Cu-FAP-2286.
4. Cohort 2: To assess the feasibility of detecting tumor uptake using FAP-2286.
5. Cohort 3: To determine the feasibility of detecting metastatic disease using FAP-2286.

EXPLORATORY OBJECTIVES

1. To detect the sensitivity of FAP-2286 PET compared to conventional imaging for the detection of metastatic disease, and when available sensitivity compared to Fluorodeoxyglucose (FDG) PET (FDG-PET).
2. Correlation of FAP-2286 uptake with FAP expression determined by immunohistochemistry.
3. Compare biodistribution of 68Ga-FAP-2286 and 64Cu-FAP-2286 in normal organs and blood pool based on renal function.
4. Determine impact of administered dose of FAP-2286 on image quality.
5. Compare the feasibility of detecting tumor uptake using 68Ga-FAP-2286 and 64Cu-FAP-2286

A repeat radiolabeled FAP-2286 PET may be obtained after initiation of subsequent treatment in order to evaluate changes in PET uptake due to treatment effect. Patients will be followed for up to 3 days after the injection of radiolabeled ligand for evaluation of adverse events.

Imaging of Solid Tumors Using FAP-2286

The frequency and severity of treatment emergent adverse events following FAP-2286 injection will be descriptively reported as classified and graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

Volumes of interest of 68Ga- and 64Cu- will be drawn around regions identified on the scans, including the liver, spleen, kidneys, urinary bladder, the central sacrum (for hematopoietic marrow) and whole body. Data will be fitted using the Simulation, Analysis, and Modeling Software II (SAAM II) software. Time integrals of activity will be entered into the Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) software, using the reference adult model. The results from all patients enrolled will be combined to allow the calculation of mean, standard deviation (SD), and range of radiation-absorbed doses to individual organs

The maximum Standardized Uptake Value (SUVmax) will be calculated for up to five lesions in each patient, with mediastinal blood pool being used as background activity.

TBR ratios will be calculated for up to five lesions in each patient, with mediastinal blood pool being used as background activity. The median and range of the measured TBRs will be reported across all RECIST measurable lesions as a table broken down by location (organ metastases, nodal metastases and bone metastases).

Conventional imaging will be reviewed in conjunction with the FAP-2286 PET images. Lesions will be characterized as positive on FAP-2286 PET if uptake is greater than 1.5 times higher than mediastinal blood pool and uptake cannot be attributed to physiologic or inflammatory reasons. Conventional imaging will be interpreted as positive by each lesion if the short axis dimension of lymph nodes is greater than 1 centimeter (cm), and organ metastases measure greater than 1 cm in long axis. The gold standard will be the combination of conventional imaging and FAP-2286 PET in combination with clinical follow-up and histopathology (if available). The number of lesions detected by each modality will be compared and sensitivity will be computed. Since this is a proof-of-concept study, it is not powered for the test of agreement. Nevertheless, the agreement will be tested using McNemar's test.

Clovis Oncology, Inc.

Thomas Hope

Principal Investigator

Fluorodeoxyglucose F18

Twelve participants with cancer and eight healthy volunteers will be recruited first to undergo whole-body PET/CT imaging to determine the whole body dosimetry of \[18F\]FluorThanatrace.

An additional 30 participants with cancer will undergo a 1-hour dynamic scan upon injection of \[18F\]FluorThanatrace to determine the kinetics of the tracer in tumors to correlate with tissue-based markers of PARP activity and to obtain metabolite information to help determine the best quantification approach for the PET images. When possible these subjects will also undergo 18F-FDG imaging for comparison to tumor metabolism

For the Dosimetry Studies, 10 mCi of \[18F\]FTT will be injected intravenously, and participants will be placed in the following groups to be imaged with PET at the specified time points: 0 minute group--image at 0 and 120 min. after tracer injection; 30 minute group--image at 30 and 150 min. after tracer injection; 60 minute group--image at 60 and 180 min. after tracer injection; and 90 minute group--image at 90 and 210 min. after tracer injection.

For the Kinetic Studies, 10 mCi of \[18F\]FTT will be injected intravenously, and a 60-minute dynamic PET scan will be obtained starting at the time of injection.

[18F]FluorThanatrace

Farrokh L Dehdashti, MD

The purpose of this research study is to determine the feasibility of using positron emission tomography (PET) imaging technology to image cancer with \[18F\]FluorThanatrace (\[18F\]FTT), a new radioactive tracer compound that has been developed that images poly(ADP-ribose) polymerase 1 (PARP-1) activity.

Poly(ADP-ribose) polymerase 1 (PARP1) is a deoxyribonucleic acid (DNA) repair enzyme that enables normal cell survival as well as certain cancers. Pharmaceutical companies have invested heavily in PARP1 inhibitor development because these agents can effectively treat certain cancers as single agents, thus sparing those patients from chemotherapy toxicities. However, clinical trials testing PARP1 inhibitors have demonstrated mixed results due to the inability to measure the degree of PARP1 inhibition in tumors reliably. Accurately measuring tumoral PARP1 activity levels before and after PARP1 inhibitor treatment will: (1) enable identification of patients whose tumors exhibit PARP activity and are therefore good candidates for PARP inhibitor therapy, and (2) confirm that adequate doses of PARP1 inhibitors are being administered to patients, thus improving dose selection for further study in clinical trials. Thus, noninvasive approaches for measuring tumoral PARP1 activity would have commercialization potential in not only supporting development of PARP1 inhibitors but also after Food and Drug Administration (FDA) approval to assess clinical PARP1 inhibitor treatment responses.

Inflammation also contributes to a number of diseases involving the lungs and other organs. Increasing evidence suggests that PARP1 may also play a central role in modulating immune inflammatory responses. Thus, the data from this trial will also be used to develop this approach for studying lung inflammatory responses.

A new radiolabeled compound, \[18F\]FluorThanatrace (\[18F\]FTT), has been generated which can be used to measure PARP1 activity noninvasively and quantitatively using positron emission tomography (PET). Our data in cancer models show that the uptake of our compound is specific for PARP1 activity and correlates with biochemically determined PARP1 activity. Additional preliminary data also suggests that decreased \[18F\]FTT uptake predicts tumor response to PARP inhibition with olaparib, a PARP1 inhibitor currently being evaluated in clinical trials. Therefore, the investigators are conducting this Phase 0 trial to develop \[18F\]FTT for clinical use in cancer patients.

To date, no biomarkers have been developed beyond genetic testing for breast cancer 1 and 2 (BRCA1/2) mutations that can aid in patient selection for treatment with PARP inhibition. Moreover, no technologies are available to monitor the efficacy of PARP inhibition. Our technology provides both a biomarker for patient selection as well as a means of monitoring PARP activity during treatment.

PET Imaging of PARP Activity in Cancer

Positron Emission Tomography (PET) Imaging of Poly(ADP-Ribose) Polymerase (PARP) Activity in Cancer

Washington University School of Medicine

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Gallium 68 PSMA-11

A single dose activity of 5 mCi (accepted range of 3-7 mCi) of 68Ga-PSMA-11 will be intravenously administered to patient as a bolus injection. After 50-100 minutes of uptake time, the patient will undergo a whole body (skull to mid-thighs) PET/CT imaging.

Positron Emission Tomography (PET) Imaging

Jeremie Calais, M.D.

To provide expanded access to 68Ga-PSMA-11 PET imaging for eligible participants to detect and localize prostate cancer for initial and subsequent treatment strategy.

Prostate-specific membrane antigen (PSMA) targeted Positron Emission Tomography (PET) imaging has been embraced enthusiastically worldwide. Given the unmet clinical need for accurately diagnosing and staging prostate cancer and the encouraging results of 68Ga-PSMA-11 PET worldwide, University of California Los Angeles (UCLA) and University of California San Francisco (UCSF) conducted pivotal registration trials to assess 68Ga-PSMA-11's safety and efficacy profile in detecting prostate cancer in adult patients. To gap the unmet clinical need of 68Ga-PSMA-11 PET during the period prior to FDA approval, UCLA Nuclear Medicine offers expanded access of this investigational PET drug to eligible participants.

Participation is not based on self-representation. Participation is based on the possession of a prostate gland.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Imaging of Solid Tumors Using FAP-2286	NCT04621435	Solid Tumors, A... Metastatic Canc...	Gallium-68 labe... Positron Emissi... Copper-64 label...	18 Years -	University of California, San Francisco
Imaging of Solid Tumors Using FAP-2286	NCT04621435	Solid Tumors, A... Metastatic Canc...	Gallium-68 labe... Positron Emissi... Copper-64 label...	18 Years -	University of California, San Francisco
PET Imaging of PARP Activity in Cancer	NCT02469129	Cancer	[18F]FluorThana...	18 Years -	Washington University School of Medicine
PET Imaging of PARP Activity in Cancer	NCT02469129	Cancer	[18F]FluorThana...	18 Years -	Washington University School of Medicine
PET Imaging of PARP Activity in Cancer	NCT02469129	Cancer	[18F]FluorThana...	18 Years -	Washington University School of Medicine
Imaging of Solid Tumors Using FAP-2286	NCT04621435	Solid Tumors, A... Metastatic Canc...	Gallium-68 labe... Positron Emissi... Copper-64 label...	18 Years -	University of California, San Francisco
Expanded Access Protocol of 68Ga-PSMA-11 for PET Imaging	NCT04348682	Prostate Cancer	Positron Emissi...	18 Years -	Jonsson Comprehensive Cancer Center

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