Glutamine PET Imaging Colorectal Cancer

Study Overview
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Brief Summary
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The clinical trial studies how well 11C-glutamine and 18F-FSPG positron emission tomography (PET) imaging works in detecting tumors in patients with metastatic colorectal cancer compared to standard imaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scanning.

Detailed Description
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PRIMARY OBJECTIVES: I. To establish and validate a 11C-glutamine (11C-Gln) and fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) PET image guided gene signature to predict response to EGFR-targeted therapy in patients with advanced wild-type RAS colorectal cancer (CRC). OUTLINE: Patients receive 11C-glutamine intravenously (IV) and undergo PET imaging over 120 minutes. Beginning 2 hours to 7 days after 11C-glutamine PET, patients receive fluorine F 18 L-glutamate derivative BAY94-9392 IV and also undergo PET imaging over 120 minutes. During each of the 11C-Glutamine and 18F-FSPG PET/CT scans, venous blood draws will be performed.

Official Title
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Glutamine PET Imaging of Colorectal Cancer

Conditions
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RAS Wild Type, Stage IV Colorectal Cancer, Stage IVA Colorectal Cancer, Stage IVB Colorectal Cancer

Intervention / Treatment
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* Biological: Carbon C 11 Glutamine
* Biological: Fluorine F 18 L-glutamate Derivative BAY94-9392
* Procedure: Positron Emission Tomography
* Procedure: Blood Draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age; Pathologically or cytologically confirmed diagnosis of metastatic (Stage IV) RAS wildtype CRC; Eligible for anti-EGFR monoclonal antibody (mAb) therapy as standard-of-care (SOC), either as a single agent or in combination with approved SOC therapies or investigational agents as part of IRB-approved clinical trials; Archived tissue from the CRC primary tumor in sufficient amounts to allow RNA-seq gene analysis; specimen from metastatic sites are not required but highly preferred; Documented results from (or scheduled to undergo) CT or MRI of the chest, abdomen and pelvis as a standard-of-care procedure within 28 days of baseline investigational 11C-Gln PET/CT and 18F-FSPG PET/CT; Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; At least one lesion >2 cm in diameter and thus will be measurable according to PET Response Criteria in Solid Tumors (PERCIST) v1.0 to avoid PET partial volume effects; Ability to provide written informed consent in accordance with institutional policies. Exclusion Criteria: Any other current or previous malignancy within the past 5 years Previous EGFR-directed therapy Body weight ≥ 400 pounds or body habitus or disability that will not permit the imaging protocol to be performed Pregnant or lactating females

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients receive carbon C 11 Glutamine (11C-glutamine) IV and undergo PET imaging over 120 minutes. Beginning 2 hours to 7 days after 11C-glutamine PET, patients receive fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) IV and also undergo PET imaging over 120 minutes. During each of the 11C-Glutamine and 18F-FSPG PET/CT scans, venous blood draws will be performed. | Biological: Carbon C 11 Glutamine<br>* Given by IV<br>Biological: Fluorine F 18 L-glutamate Derivative BAY94-9392<br>* Given by IV<br>Procedure: Positron Emission Tomography<br>* Undergo PET scan<br>Procedure: Blood Draw<br>* Undergo venous blood draws<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pet imaging | Assessed in terms of Standardized Uptake Values (SUVs) | Baseline prior to treatment with anti-EGFR mAb | 
| Pharmacokinetic rate constants for 11C-Glutamine and 18F-FSPG | The pharmacokinetic rate constants for 11C-Glutamine and 18F-FSPG will be determined using compartmental modeling of PET imaging data. Venous samples will be collected over the course of both 11C-Glutamine and 18F-FSPG scans for use in modeling. | Baseline prior to treatment with anti-EGFR mAb | 
| Change in tumor size | Change in tumor size will be derived from standard-of-care computed tomography (CT) or magnetic resonance imaging (MRI). The tumor size will be reported as either the long-axis diameter or as tumor volume. | Baseline prior to treatment with anti-EGFR mAb and every 8 weeks while on treatment (after every two (2) cycles of anti-EGFR mAb therapy (each cycle is 4 weeks)); through treatment completion, an average of 24 weeks (6 cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expression | Gene expression will be determined using RNA-Seq of archived primary (and if available, metastatic) tissues. | Prior to treatment with anti-EGFR mAb | 
| Progression free survival | Progression-free survival is defined as the time from start of therapy to disease progression by RECIST criteria or death for any reason. | every 8 weeks while on treatment (after every two (2) cycles of anti-EGFR mAb therapy (each cycle is 4 weeks)); Up to 4 years after treatment | 
| Overall survival | Overall survival is defined as the time from start of treatment to death for any reason. | Up to 4 years after treatment |