Chemoimmunotherapy Combined With Hyperthermia and Spatially-Fractionated Radiotherapy in Advanced Biliary Tract Cancer
NCT Number: NCT06546969
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Biliary Tract Cancer
Interventions: DRUG: Gemcitabine|DRUG: Cisplatin|DRUG: Durvalumab|RADIATION: Spatially Fractionated RT|DEVICE: Deep Hyperthermia
Sponsor: University of Maryland, Baltimore
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 15
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10
Completion Date: 2028-12
Locations: Maryland Proton Treatment Center, Baltimore, Maryland, 21201, United States|University of Maryland Greenebaum Cancer Center, Baltimore, Maryland, 21201, United States

Summary:
This study is being done to see if the investigators can improve the outcome of patients with biliary tract cancer that do not qualify for surgery. This study will compare the effects, good and/or bad, of using a combination of standard of care chemoimmunotherapy, with the addition of radiation and deep hyperthermia. In this study, participants will be receiving standard of care chemoimmunotherapy (gemcitabine, cisplatin, and durvalumab), radiation (spatially fractionated radiation therapy), and deep hyperthermia.

Chemoimmunotherapy Chemoimmunotherapy is when chemotherapy drugs are combined with immunotherapy drugs. Chemotherapy uses different drugs to kill or slow the growth of cancer cells, whereas immunotherapy drugs are used to help the immune system attack cancer cells. For this study, the drugs Gemcitabine, Cisplatin, and Durvalumab will be used. Chemoimmunotherapy will be delivered over 4 cycles for this study and can continue longer if the treating physician decides this is appropriate. Each cycle will last 3 weeks.

Spatially fractionated radiation therapy (SFRT) SFRT is a form of radiation therapy that gives a single large dose of radiation to large tumors or tumors that do not qualify for surgery. This is not a standard type of treatment for people with this diagnosis. For this study, participants will be receiving radiation once on day 1 of the second chemoimmunotherapy cycle.

Deep Hyperthermia (HT) Hyperthermia is used in combination with chemoimmunotherapy and radiation treatment in this study. Hyperthermia has the potential to make both chemotherapy and radiation treatments more effective. For this study, participants will receive HT three times: on the first day of cycles 2, 3, and 4 of chemoimmunotherapy.

Primary Outcome Measures: Number of adverse events assessment by CTCAE v5.0 that are grade 3 or higher and related to HT or SFRT, Determine the safety of combined deep hyperthermia, spatially-fractionated radiotherapy and chemoimmunotherapy in this patient population

Safety is defined by \< 30% rate of grade 3 or higher non-hematologic adverse events possibly or probably related to deep HT or SFRT from cycle 2-day 1 until 90 days post the final deep HT treatment. A rolling safety evaluation will be performed during patient enrollment and termination of the study will occur if any of the below are met

* Grade 3+ adverse events in more than 1 of the first 3 or 2 of the first 6 patients possibly or probably related to deep HT or SFRT
* Grade 4+ adverse event in more than 3 total patients possibly or probably related to deep HT or SFRT
* Grade 5 adverse event in 1 patient where the event is not clearly attributable to the underlying disease or extraneous causes., 90 days post final treatment of Deep Hyperthermia|Number of participants to receive a minimum of 30 minutes of heating at target temperature (39-43°C) for at least 2 of the planned 3 deep HT treatments, Estimate the feasibility of administering combined deep hyperthermia, spatially-fractionated radiotherapy and chemoimmunotherapy for subjects with advanced biliary tract cancer not amenable to surgical resection or definitive local therapy.

Feasibility is defined as the ability of participants to receive a minimum of 30 minutes of heating at target temperature (39-43°C) for at least 2 of the planned 3 deep HT treatments. A single-group design will be used to obtain a two-sided 95% confidence interval for a single proportion (feasibility). The Exact Clopper-Pearson approach will be used to calculate the confidence interval. The sample proportion is assumed to be 0.7. To produce a confidence interval with a width of no more than 0.5, 15 subjects will be needed., 90 days post final treatment
Secondary Outcome Measures: Radiographic Response Rate, Estimate the radiographic response rate at the 16 week imaging timepoint.

All participants who undergo at least 1 imaging assessment after beginning study will be eligible for radiographic response estimation per RECIST version 1.1 by local radiology review. Baseline CT or MRI scans will be used to select target and non-target lesions., 16 weeks from start of treatment
Other Outcome Measures: Measure absolute number of immune cell subsets, Exploratory Objective: To assess blood-based correlates of immunity prior to and during treatment for participants on study.

Immune correlates, through blood sampling, will be measured within 4 weeks of enrollment and approximately every 8 weeks through week 16 to evaluate the degree of immune activation. These analyses will evaluate the absolute number, distribution, and activation status of immune cell subsets, 1 year post completion of accrual|Measure distribution of immune cell subsets, Exploratory Objective: To assess blood-based correlates of immunity prior to and during treatment for participants on study.

Immune correlates, through blood sampling, will be measured within 4 weeks of enrollment and approximately every 8 weeks through week 16 to evaluate the degree of immune activation. These analyses will evaluate the absolute number, distribution, and activation status of immune cell subsets, 1 year post completion of accrual|Measure activation status of immune cell subsets, Exploratory Objective: To assess blood-based correlates of immunity prior to and during treatment for participants on study.

Immune correlates, through blood sampling, will be measured within 4 weeks of enrollment and approximately every 8 weeks through week 16 to evaluate the degree of immune activation. These analyses will evaluate the absolute number, distribution, and activation status of immune cell subsets, 1 year post completion of accrual