Evaluation of treatment response for immune checkpoint inhibitors using [ 18F]F-AraG PET/CT

JRCT ID: jRCTs051240253

Registered date:28/01/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Malignant tumor
• Date of first enrollment: 28/01/2025
• Target sample size: 60
• Study type: Interventional

Intervention(s)

Here is the English translation:

1. The first [18F]F-AraG PET scan will be performed within 2 weeks of the initial administration of immune checkpoint inhibitors.
2. The second [18F]F-AraG PET scan will be performed between 3 to 7 days after the initial administration of immune checkpoint inhibitors.
3. If an endoscopic examination is possible for gastrointestinal cancer, a tumor biopsy will be performed approximately 7 to 10 weeks after the initial administration of immune checkpoint inhibitors.

Outcome(s)

Primary Outcome

By performing [18F]F-AraG PET before and after the initial ICI (immune checkpoint inhibitor) treatment, we will evaluate whether the change in [18F]F-AraG accumulation in the primary lesion (the difference in the maximum SUVmax between the first and second scans: delta-SUVmax) can predict the effectiveness of ICI treatment (SUV = Standardized Uptake Value). The group with increased [18F]F-AraG accumulation will be examined to see if they maintain non-PD status for a longer period with ICI compared to the group with decreased [18F]F-AraG accumulation, meaning that the former group may show a more prolonged positive response to ICI treatment (for malignant tumors undergoing surgery, whether they have a higher pCR rate), using the chi-squared test.
Simultaneously, to explore the cutoff value of delta-SUVmax that most effectively predicts treatment response, the population will be divided into two groups based on the median non-PD duration, and an ROC curve will be created using the change in [18F]F-AraG accumulation as a continuous variable. The significance level for all analyses will be set at 5%.

Secondary Outcome

For biopsy specimens (primary lesion and lymph nodes) obtained through routine clinical care, we will compare the accumulation seen in the first [18F]F-AraG PET with the positive rates of CD8 and PD-1 positive cells. Spearman's rank correlation coefficients will be calculated for each, and we will check for significant correlations. The indicators of [18F]F-AraG PET accumulation will include the maximum value in the region of interest (SUVmax), the average value in the region of interest (SUVmean), and the value obtained by multiplying the volume of the region of interest by SUVmean. For each indicator, the correlation coefficient with CD8 and PD-1 positive cells will be calculated. The significance level will be set at 5%.

* Comparison with [18F]FDG PET
For [18F]FDG PET performed through routine clinical care, the correlation between the positive rate of CD8 and PD-1 positive cells in the biopsy specimen (primary lesion and lymph nodes) will also be calculated using Spearman's rank correlation coefficient. The indicators of [18F]FDG PET accumulation will include the maximum value in the region of interest (SUVmax), the average value in the region of interest (SUVmean), and the value obtained by multiplying the volume of the region of interest by SUVmean. Given that [18F]FDG PET is taken up by not only immune cells but also cancer cells, the correlation is hypothesized to be weaker. A comparison of accumulation in immune tissues such as the spleen and bone marrow will also be conducted.

* (Only if tissue is obtained after ICI treatment) Comparison between the second [18F]F-AraG accumulation and primary lesion tissue
If a tissue examination is performed through surgery or endoscopy after the second [18F]F-AraG PET, the obtained tissue specimen will be compared with the second [18F]F-AraG accumulation. Specifically, we will examine whether there is a correlation between CD8 and PD-1 expression in the tissue and F-AraG accumulation.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

(1) The patient has been diagnosed with a malignant tumor based on histological examination.
(2) The patient is clinically eligible for immune checkpoint inhibitors approved in Japan, and the treatment is planned.
(3) The patient has undergone, or is scheduled to undergo, [18F]FDG-PET.
(4) The patient has an ECOG Performance Status (PS) of 0, 1, or 2.

Exclude criteria

Here is the English translation:

1. Women who are pregnant or may be pregnant, and women who are breastfeeding.
2. Individuals in extremely poor general condition (such as abnormal vital signs) or with significant communication impairments.
3. Those diagnosed with Li-Fraumeni syndrome.
4. Other patients deemed inappropriate as research subjects by the principal investigator, the responsible physician, or the co-investigator.

Related Information

• Primary Sponsor: Nakamoto Yuji
• Secondary Sponsor: Nobashi W Tomomi