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

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.

• 18F-fludeoxyglucose (18F-FDG) (Drug), also known as Fludeoxyglucose F-18, 18-FDG, FDG: 18F-FDG will be used as the radiotracer for a regular medical care PET/CT or PET/MRI scan
• 18F-FPPRGD2 (Drug), also known as (18F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid peptide, [PEG3-E{c(RGDyk)}2], fluorine-18-FPPRGD2, [18F]-FPPRGD2, 2-fluoropropionyl-labeled pegylated dimeric RGD peptide, 104150: 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.

Primary outcomes

• Change From Baseline in Maximum Standard Uptake Values (SUVmax) [At baseline and 6 weeks]: 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.

Secondary outcomes

• Response Assessment by RANO Criteria [At baseline and 6 weeks]: 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
• Change in Tumor Size [9 to 12 weeks]: 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.
• Tumor Response Rate by EORTC Criteria [At baseline and 6 weeks]: 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
• Progression-free Survival (PFS) [1 year]: 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.

Sex: All, ages: 18 Years to any

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)

Participant flow

Outcome results

• Change From Baseline in Maximum Standard Uptake Values (SUVmax) (Primary), Median, ratio: Glioblastoma Multiforme (GBM) -0.98 +/- 0.98; Gynecological Cancers 0.09 +/- 1.20; Renal Cell Cancer (RCC) 0.10 +/- 0.29
• Response Assessment by RANO Criteria (Secondary)
• Change in Tumor Size (Secondary), Median, centimeters: Glioblastoma Multiforme (GBM) ; Gynecological Cancers 0.9 +/- 1.56; Renal Cell Cancer (RCC) 1 +/- 1.56
• Tumor Response Rate by EORTC Criteria (Secondary), Number, participants: Glioblastoma Multiforme (GBM) ; Gynecological Cancers 2; Renal Cell Cancer (RCC) 0
• Progression-free Survival (PFS) (Secondary)

Adverse events

Time frame: 6 weeks

Serious adverse events by term

• Results publication: Minamimoto R, Jamali M, Barkhodari A, Mosci C, Mittra E, Shen B, Chin F, Gambhir SS, Iagaru A. Biodistribution of the (1)(8)F-FPPRGD(2) PET radiopharmaceutical in cancer patients: an atlas of SUV measurements. Eur J Nucl Med Mol Imaging. 2015 Nov;42(12):1850-8. doi: 10.1007/s00259-015-3096-4. Epub 2015 Jun 11. PMID 26062933
• Results publication: Iagaru A, Mosci C, Mittra E, Zaharchuk G, Fischbein N, Harsh G, Li G, Nagpal S, Recht L, Gambhir SS. Glioblastoma Multiforme Recurrence: An Exploratory Study of (18)F FPPRGD2 PET/CT. Radiology. 2015 Nov;277(2):497-506. doi: 10.1148/radiol.2015141550. Epub 2015 May 12. PMID 25965900
• Results publication: Minamimoto R, Karam A, Jamali M, Barkhodari A, Gambhir SS, Dorigo O, Iagaru A. Pilot prospective evaluation of (18)F-FPPRGD2 PET/CT in patients with cervical and ovarian cancer. Eur J Nucl Med Mol Imaging. 2016 Jun;43(6):1047-55. doi: 10.1007/s00259-015-3263-7. Epub 2015 Nov 27. PMID 26611425
• Results publication: Toriihara A, Duan H, Thompson HM, Park S, Hatami N, Baratto L, Fan AC, Iagaru A. 18F-FPPRGD2 PET/CT in patients with metastatic renal cell cancer. Eur J Nucl Med Mol Imaging. 2019 Jul;46(7):1518-1523. doi: 10.1007/s00259-019-04295-7. Epub 2019 Mar 8. PMID 30850872

• Sanjiv Gambhir, MD, PhD, Principal investigator, Stanford University