Pafolacianine Imaging for Gastrointestinal Cancer

Overseen By Chao Family Comprehensive Cancer Center University of California, Irvine

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Irvine

Disqualifiers: Inoperable cancer, Anaphylactic history, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Pafolacianine for gastrointestinal cancer?

Pafolacianine has shown effectiveness in helping surgeons see certain types of cancer more clearly during surgery, as demonstrated in studies involving lung and ovarian cancers. This suggests it might also help in surgeries for gastrointestinal cancers by making cancerous areas more visible. ^{1 2 3 4 5}

How is the drug Pafolacianine unique for gastrointestinal cancer imaging?

Pafolacianine is unique because it is used specifically for imaging, helping to visualize cancerous tissues during surgery, which can improve the precision of tumor removal. This differs from other treatments that primarily focus on treating the cancer rather than enhancing surgical outcomes. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a pilot, single-arm, open label study to evaluate the ability of CYTALUX™ (pafolacianine) to help identify cancerous lesions in subjects with gastrointestinal cancers and peritoneal carcinomatosis during cytoreductive surgery.

Research Team

Maheswari Senthil, MD

Principal Investigator

Chao Family Comprehensive Cancer Center

Eligibility Criteria

This trial is for individuals with gastrointestinal cancers and peritoneal carcinomatosis. Participants should be candidates for cytoreductive surgery, which aims to remove visible tumors from the abdomen.

Inclusion Criteria

I am a woman and have had negative pregnancy tests before receiving study treatment or surgery.

Ability to understand the requirements of the study, provide written informed consent for participation in the study and authorization of use and disclosure of protected health information, and agree to abide by study restrictions

My cancer originates in the gastrointestinal tract and I am scheduled for surgery to remove it.

Exclusion Criteria

Clinically significant abnormalities on ECG

My liver tests are more than three times the normal limit.

My kidney function is reduced with an eGFR below 50.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of pafolacianine (CYTALUX) prior to intraoperative imaging during cytoreductive surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events

30 days

Long-term Follow-up

Participants are monitored for primary outcome measures such as sensitivity, specificity, and accuracy over a longer period

1 year

Treatment Details

Interventions

• Pafolacianine

Trial Overview The study tests CYTALUX (pafolacianine) used during surgery to see if it can better highlight cancerous tissues using a special camera that detects its fluorescent glow under near-infrared light.

Participant Groups

Group I: Pafolacianine (CYTALUX) Experimental Treatment 1 Intervention

All subjects will receive one single intravenous infusion of 0.025 mg/kg of pafolacianine (CYTALUX) injection prior to anticipated intraoperative imaging planned for cytoreductive surgery.

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

On Target Laboratories

Collaborator

Trials

2

Recruited

30+

Findings from Research

FDG-PET scanning is a highly effective diagnostic tool for gastrointestinal cancers, particularly in staging oesophageal carcinoma and detecting recurrence in colorectal carcinoma, with sensitivity rates reaching up to 100%.

The technique is also valuable for differentiating between benign and malignant pancreatic lesions, showing high sensitivity and specificity, making it a crucial part of cancer diagnosis and treatment monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDG-PET scanning in the diagnosis of gastrointestinal cancers. van Kouwen, MC., Oyen, WJ., Nagengast, FM., et al.[2019]

In a study of 38 patients with suspected lung cancer, preoperative staining for folate receptors (FRα and FRβ) was found to correlate with the effectiveness of pafolacianine fluorescence during surgery, indicating that higher FRα expression is associated with better fluorescence detection of malignant tumors.

The results showed that 95% of malignant tumors fluoresced during surgery, while none of the benign tumors did, suggesting that FRα IHC could be a useful tool for selecting patients who would benefit from pafolacianine-guided surgery, warranting further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective validation of tumor folate receptor expression density with the association of pafolacianine fluorescence during intraoperative molecular imaging-guided lung cancer resections. Azari, F., Zhang, K., Kennedy, G., et al.[2023]

In a Phase 3 trial involving 112 lung cancer patients, the use of pafolacianine for intraoperative molecular imaging significantly improved surgical outcomes by identifying hidden tumors and narrow margins, with 53% of participants experiencing clinically significant events compared to a 10% threshold.

No serious adverse events were reported from pafolacianine, indicating its safety, while it successfully located primary nodules that were undetectable by conventional methods in 19% of cases and revealed additional malignant lesions in 8% of subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pafolacianine for intraoperative molecular imaging of cancer in the lung: The ELUCIDATE trial. Sarkaria, IS., Martin, LW., Rice, DC., et al.[2023]

In a phase III study involving 150 patients with ovarian cancer, pafolacianine successfully identified additional cancerous lesions in 33% of cases that were not detected by traditional methods, demonstrating its efficacy as an adjunctive tool during surgery.

The use of pafolacianine was found to be safe, with no serious drug-related adverse events reported, although 30% of patients experienced mild side effects like nausea and abdominal pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006). Tanyi, JL., Randall, LM., Chambers, SK., et al.[2023]

In a study of 32 patients with digestive system tumors, 68 Ga-FAPI-04 PET/CT imaging resulted in staging changes for nearly 47% of patients, indicating its potential to provide more accurate tumor assessments compared to standard imaging methods.

The use of FAPI-directed imaging led to therapeutic management changes in 25% of cases, particularly benefiting patients with hepatocellular carcinoma (HCC) and pancreatic duct adenocarcinoma (PDAC), suggesting it could enhance treatment strategies for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of 68 Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors. Kosmala, A., Serfling, SE., Schlötelburg, W., et al.[2023]

FAPI PET imaging outperformed traditional FDG PET/CT/MRI in detecting tumors and metastases in patients with pancreatic, gastric, and cholangiocarcinoma, based on a systematic review of 10 studies.

FAPI PET provided higher maximum standardized uptake values (SUVmax) and tumor-to-background ratios (TBRmax), indicating its potential for more accurate cancer staging and diagnosis, which supports the need for further clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FAPI PET versus FDG PET, CT or MRI for Staging Pancreatic-, Gastric- and Cholangiocarcinoma: Systematic Review and Head-to-Head Comparisons of Diagnostic Performances. Veldhuijzen van Zanten, SEM., Pieterman, KJ., Wijnhoven, BPL., et al.[2022]

Fluorine 18-fluorodeoxyglucose PET (FDG-PET) is a valuable noninvasive imaging technique that enhances cancer diagnosis and treatment by detecting increased glucose metabolism in tumors, aiding in staging and assessing treatment response.

Emerging metabolic PET imaging agents, such as amino acid analogs and choline, offer greater specificity for tumor cells compared to FDG, making them useful for identifying cancers that may not show high FDG uptake, thus improving diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic positron emission tomography imaging in cancer detection and therapy response. Zhu, A., Lee, D., Shim, H.[2021]

The newly developed dipeptides [18F]Gly-4F-Gln and [18F]Ala-4F-Gln rapidly convert to the active imaging agent (2S,4R)-4-[18F]fluoroglutamine in the bloodstream, indicating their potential as effective prodrugs for tumor imaging.

Both dipeptides showed rapid localization in tumor tissues during PET imaging in rat models, with [18F]Ala-4F-Gln being particularly promising for imaging glutaminolysis in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alanine and glycine conjugates of (2S,4R)-4-[18F]fluoroglutamine for tumor imaging. Zha, Z., Ploessl, K., Lieberman, BP., et al.[2019]

In a study of 15 patients with advanced gastric cancer, MR imaging using tap water as an oral contrast agent was found to be as effective as gadopentetate dimeglumine (Gd-DTPA) for evaluating the cancer, suggesting that Gd-DTPA may not be necessary.

FLASH imaging provided slightly better image quality and diagnostic accuracy for T-staging compared to other MR techniques, while HASTE and true FISP imaging showed superior contrast-to-noise ratios, indicating that a combination of these methods can enhance evaluation of advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR imaging of advanced gastric cancer: comparison of various MR pulse sequences using water and gadopentetate dimeglumine as oral contrast agents. Kim, AY., Han, JK., Kim, TK., et al.[2019]

In a study of 33 patients with suspected recurrent pancreatic ductal adenocarcinoma (PDAC), both early (20 min) and late (60 min) 68Ga-FAPI-PET imaging provided similar detection rates for most lesions, indicating that either timepoint can be effective for imaging.

However, early imaging was more effective for detecting cholestatic lesions, suggesting that using both timepoints may enhance diagnostic accuracy and help differentiate between types of lesions in recurrent PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of early and late 68Ga-FAPI-46-PET in 33 patients with possible recurrence of pancreatic ductal adenocarcinomas. Hoppner, J., van Genabith, L., Hielscher, T., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

FDG-PET scanning in the diagnosis of gastrointestinal cancers. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Prospective validation of tumor folate receptor expression density with the association of pafolacianine fluorescence during intraoperative molecular imaging-guided lung cancer resections. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Pafolacianine for intraoperative molecular imaging of cancer in the lung: The ELUCIDATE trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006). [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Impact of 68 Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

FAPI PET versus FDG PET, CT or MRI for Staging Pancreatic-, Gastric- and Cholangiocarcinoma: Systematic Review and Head-to-Head Comparisons of Diagnostic Performances. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Metabolic positron emission tomography imaging in cancer detection and therapy response. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Alanine and glycine conjugates of (2S,4R)-4-[18F]fluoroglutamine for tumor imaging. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

MR imaging of advanced gastric cancer: comparison of various MR pulse sequences using water and gadopentetate dimeglumine as oral contrast agents. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Comparison of early and late 68Ga-FAPI-46-PET in 33 patients with possible recurrence of pancreatic ductal adenocarcinomas. [2023]