Cholangiocarcinoma
Conditions
Brief summary
This phase II trial studies whether \[18F\]FTT can be used with positron emission tomography (PET)/computed tomography (CT) imaging to predict treatment response in patients scheduled to receive gemcitabine, cisplatin, and durvalumab (GCD) for newly diagnosed cholangiocarcinoma. PET/CT is an imaging technique that utilizes PET and CT in a single machine. PET is an established imaging technique that utilizes small amounts of radioactivity attached to very minimal amounts of tracer, in the case of this trial, \[18F\]FTT, to make detailed, computerized pictures of areas inside the body where the tracer is used. CT utilizes x-rays that traverse body from the outside. CT images provide an exact outline of organs and potential inflammatory tissue where it occurs in the patient's body. \[18F\]FTT targets and binds to poly (ADP-ribose) polymerase 1 (PARP1). Some cholangiocarcinoma tumor cells may express PARP1 which may make it easier to see them on PET/CT. Research has shown that tumor cells that express PARP1 may not respond well to GCD treatment. Researchers hope that by using \[18F\]FTT with PET/CT imaging they will be able to detect which patients have tumor cells that express PARP1, which may help predict treatment response in patients scheduled to receive GCD for newly diagnosed cholangiocarcinoma.
Detailed description
OUTLINE: Patients receive \[18F\]FTT intravenously (IV) and 60, 90, or 150 minutes later undergo PET/CT within 30 days prior to day 1 cycle 1 of GCD and 12 weeks after starting GCD in the absence of unacceptable toxicity. Patients also undergo CT and/or magnetic resonance imaging (MRI) throughout the study. After completion of study intervention, patients are followed up at week 24 and then up to 6 months after completing GCD treatment.
Interventions
PROCEDUREComputed Tomography
Undergo PET/CT and/or CT
RADIATIONFluorine F 18 Fluorthanatrace
Given IV
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
PROCEDUREPositron Emission Tomography
Undergo PET/CT
Sponsors
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must have histologically confirmed cholangiocarcinoma * Patient must be newly diagnosed and have not yet been treated * Patient planned to receive GCD per standard-of-care * Patient must have evaluable disease or at least one measurable lesion that can be assessed at baseline by CT (or MRI) per RECIST 1.1 * Age ≥ 18 years * For women of childbearing potential, a negative serum pregnancy test is required within 7 days prior to \[18F\]FTT PET imaging * Men and women of reproductive potential need to agree to employ acceptable forms of contraception throughout their participation in the study that meet requirements for GCD treatment per standard of care * Patient is willing and able to comply with the protocol for the duration of the study including undergoing all study procedures * Ability to understand and the willingness to sign a written informed consent document. Informed consent must be provided prior to any study specific procedures
Exclusion criteria
* Pregnant or breastfeeding women * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relationship between standardized uptake value maximum (SUVmax) and overall response rate | At baseline and 24 weeks after starting gemcitabine, cisplatin, and durvalumab (GCD) | Baseline SUVmax will be extracted from a region of interest (ROI) placed on the tumor lesion of interest using a 40% threshold. Will assess overall response rate at 24 ± 2 weeks after starting GCD by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Response will be analyzed as a binary outcome. Differences in baseline SUVmax between responders and non-responders will be evaluated using the Wilcoxon rank-sum test. Logistic regression models will be used to estimate the direction and magnitude of association, with response as the dependent variable and SUVmax as the predictor. Odds ratios and 95% confidence intervals will be reported. Analysis will focus on estimation of effect sizes and the direction and magnitude of associations of the primary endpoints, overall response rate and SUVmax of the most avid lesion, rather than formal hypothesis testing alone. Boxplots will be used to visualize the distribution of SUVmax by responders group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relationship between standardized uptake value mean (SUVmean) and overall response rate | At baseline and 24 weeks after starting GCD | Will measure baseline SUVmean from an ROI placed on the tumor lesion of interest using a 40% threshold. Treatment response will be defined by RECIST 1.1 criteria at 24 ± 2 weeks following GCD treatment. Association between baseline SUVmean and treatment response will be evaluated using Wilcoxon rank-sum test. Logistic regression will be used to quantify the magnitude and direction of association between baseline SUVmean and response. Results will be summarized using odds ratios with 95% confidence intervals, and boxplot to illustrate the distribution of baseline SUVmean between responders and non-responders. |
| Change in SUVmax and response | Baseline to 12 weeks after starting GCD | Will calculate the change of SUVmax from baseline to 12 ± 2 weeks after starting GCD. Due to the limited sample size, will use the nonparametric method Wilcoxon Rank Sum test to evaluate the difference in change between responders and non-responders. Effect sizes will be summarized using the median difference (Hodges-Lehmann estimator) in change between groups with 95% confidence intervals. |
| Change in SUVmean and response | Baseline to 12 weeks after starting GCD | Will calculate the change of SUVmean from baseline to 12 ± 2 weeks after starting GCD. Due to the limited sample size, will use the nonparametric method Wilcoxon Rank Sum test to evaluate the difference in change between responders and non-responders. Effect sizes will be summarized using the median difference (Hodges-Lehmann estimator) in change between groups with 95% confidence intervals. |
Countries
United States
Contacts
CONTACTAngela Castellanos Rodriguez, MD, MSc
PRINCIPAL_INVESTIGATORAngela Castellanos Rodriguez, MD, MSc
Fred Hutch/University of Washington Cancer Consortium
Outcome results
None listed