18F-FPPRGD2 PET/CT or PET/MRI in Predicting Early Response in Patients With Cancer Receiving Anti-Angiogenesis Therapy

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to conduct research of a new PET radiopharmaceutical in cancer patients. The uptake of the novel radiopharmaceutical 18F-FPPRGD2 will be assessed in study participants with glioblastoma multiforme (GBM), gynecological cancers, and renal cell carcinoma (RCC) who are receiving antiangiogenesis treatment.

Detailed Description
-----------------
PRIMARY OBJECTIVE • Evaluate 18F-FPPRGD2 and 18F-FDG as PET/CT or PET/MRI radiotracers for imaging prediction and assessment of response to anti-angiogenesis therapy in participants with glioblastoma multiforme (GBM), gynecological cancers, and renal cell carcinoma (RCC). SECONDARY OBJECTIVE • Progression-free survival (PFS) at up to 1 year after initial scans and treatment OUTLINE: Patients undergo 18F-FPPRGD2 and 18F-FDG PET/CT or PET/MRI medical imaging at baseline and at regular medical care follow-up (6 to 12 weeks). After completion of study imaging, patients are followed up at 12 months.

Official Title
-----------------
Phase 1-2 18F-FPPRGD2 PET/CT or PET/MRI Imaging of αvβ3 Integrins Expression as a Biomarker of Angiogenesis

Conditions
-----------------
Tongue Cancer, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Male Breast Cancer, Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Adult Brain Tumor, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Colon Cancer, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Hypopharyngeal Cancer, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Recurrent Laryngeal Cancer, Recurrent Lip and Oral Cavity Cancer, Recurrent Lymphoepithelioma of the Nasopharynx, Recurrent Lymphoepithelioma of the Oropharynx, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Recurrent Mucoepidermoid Carcinoma of the Oral Cavity, Recurrent Nasopharyngeal Cancer, Recurrent Non-small Cell Lung Cancer, Recurrent Oropharyngeal Cancer, Recurrent Pancreatic Cancer, Recurrent Paranasal Sinus and Nasal Cavity Cancer, Recurrent Rectal Cancer, Recurrent Renal Cell Cancer, Recurrent Salivary Gland Cancer, Stage IIIA Breast Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Breast Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer, Stage IV Non-small Cell Lung Cancer, Stage IV Pancreatic Cancer, Stage IV Renal Cell Cancer, Stage IVA Colon Cancer, Stage IVA Rectal Cancer, Stage IVA Salivary Gland Cancer, Stage IVB Colon Cancer, Stage IVB Salivary Gland Cancer, Stage IVC Salivary Gland Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Drug: 18F-fludeoxyglucose (18F-FDG)
* Drug: 18F-FPPRGD2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provides written informed consent Diagnosed with advanced NSCLC, breast cancer, GBM or other cancers (such as head and neck, colorectal, pancreatic, renal cancers); patients will undergo anti-angiogenesis treatment or treatment with other drugs that may alter angiogenesis Able to remain still for duration of each imaging procedure (about one hour) Exclusion Criteria: Pregnant or nursing Contraindication to MRI History of renal insufficiency (only for MRI contrast administration)

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

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

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

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

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glioblastoma Multiforme (GBM)<br>Patients with glioblastoma multiforme (GBM) undergo 18F-FDG and 18F-FPPRGD2 positron emission tomography / computed tomography (PET/CT) imaging at baseline and 6 weeks (or standard of care follow-up) | Drug: 18F-fludeoxyglucose (18F-FDG)<br>* 18F-FDG will be used as the radiotracer for a regular medical care PET/CT or PET/MRI scan<br>* Other names: FDG;Drug: 18F-FPPRGD2<br>* 18F-FPPRGD2 will be used as the radiotracer for a PET/CT or PET/MRI scan. Participants will be injected with less than 10 mCi of 18F-FPPRGD2.<br>* Other names: 104150;|
| Experimental: Gynecological Cancers<br>Patients with gynecological cancer undergo 18F-FDG and 18F-FPPRGD2 positron emission tomography / computed tomography (PET/CT) imaging at baseline and at 9 t0 12 weeks (or standard of care follow-up) | Drug: 18F-fludeoxyglucose (18F-FDG)<br>* 18F-FDG will be used as the radiotracer for a regular medical care PET/CT or PET/MRI scan<br>* Other names: FDG;Drug: 18F-FPPRGD2<br>* 18F-FPPRGD2 will be used as the radiotracer for a PET/CT or PET/MRI scan. Participants will be injected with less than 10 mCi of 18F-FPPRGD2.<br>* Other names: 104150;|
| Experimental: Renal Cell Cancer (RCC)<br>Patients with renal cell cancer (RCC) undergo 18F-FDG and 18F-FPPRGD2 positron emission tomography / computed tomography (PET/CT) imaging at baseline and at 9 t0 12 weeks (or standard of care follow-up) | Drug: 18F-fludeoxyglucose (18F-FDG)<br>* 18F-FDG will be used as the radiotracer for a regular medical care PET/CT or PET/MRI scan<br>* Other names: FDG;Drug: 18F-FPPRGD2<br>* 18F-FPPRGD2 will be used as the radiotracer for a PET/CT or PET/MRI scan. Participants will be injected with less than 10 mCi of 18F-FPPRGD2.<br>* Other names: 104150;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Maximum Standard Uptake Values (SUVmax) | Maximum standard uptake values (SUVmax) were assessed on the basis of position emission tomography (PET) scans using radiotracers 18F-FPPRGD2 and 18F-FDG at baseline and at regular medical care follow-up (6 to 12 weeks after initiation of treatment). The outcome is assessed as the difference in the maximum standard uptake values (SUVmax) values from baseline to follow-up for the 2 radiotracers, and will be reported for each disease type as the median with standard deviation. | At baseline and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Assessment by RANO Criteria | The treatment effect for participants with glioblastoma multiforme was to be assessed on the basis of post-treatment evaluation per the Response Assessment in Neuro-Oncology (RANO) Criteria. The outcome was the number & proportion of participants that achieved either a complete response (CR) or partial response (PR), a number without dispersion. RANO criteria are: CR= No T1 gadolinium (T1-G); T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) stable/decreased, no new lesions; no corticosteroids; clinical condition improved/stable. PR= ≥50% decrease in T1-G; T2/FLAIR decreased/stable ; no new lesions; decreased/stable corticosteroids; clinical condition improved/stable. Stable disease (SD)= <50% decrease, but more than 25% increase, in T1-G; T2/FLAIR decreased/stable; no new lesions; decreased/stable corticosteroids; clinical condition improved/stable. Progressive disease (PD)= ≥25%increase T1-G; T2/FLAIR increased; increased corticosteroids; clinical condition decreased | At baseline and 6 weeks | 
| Change in Tumor Size | The treatment effect for participants with gynecological cancers (GYN) and renal cell carcinoma (RCC) was assessed on the basis of change in tumor size as determined by pre- and post-treatment CT scans. The outcome is reported as the difference at treatment follow-up, reported as the median with standard deviation. | 9 to 12 weeks | 
| Tumor Response Rate by EORTC Criteria | Tumor Response Rate by EORTC Criteria Tumor response rates were assessed from position emission tomography (PET) scans using 18F-FPPRGD2 & 18F-FDG at baseline & after 6 weeks of treatment, per European Organization for Research & Treatment of Cancer (EORTC) response criteria. The outcome is reported for each radiotracer by disease group as the number of participants achieving complete response (CR), partial response (PR), stable disease (SD), & progressive disease (PD). CR= complete resolution of 18F-FDG uptake tumor volume PR= reduction of 15-25% in tumor 18F-FDG SUVmax after 1 cycle of chemotherapy, and ≥25% after >1 cycle SD= increase in tumor 18F-FDG SUVmax of <25% or a decrease of <15% & no increase in 18F-FDG tumor uptake [>20% in the longest dimension (LD)]; PD= increase in 18F-FDG tumor SUVmax of >25% in tumor region on baseline; increase in extent of 18F-FDG tumor uptake (>20% in LD); appearance of new 18F-FDG uptake in metastatic lesions | At baseline and 6 weeks | 
| Progression-free Survival (PFS) | Progression-free survival (PFS) was defined as remaining alive at 1 year with disease progression, according to the physician's assessment of clinical status, by disease group. | 1 year |