Chemoimmunotherapy Combined With Hyperthermia and Spatially-Fractionated Radiotherapy in Advanced Biliary Tract Cancer

Recruiting now · Phase 1

Conditions studied: Biliary Tract Cancer, Cholangiocarcinoma

In brief

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.

Key facts

Study ID

NCT06546969

Run by

University of Maryland, Baltimore

People needed

15

Starts

2024-10-29

Expected to finish

2028-12-01

Last updated by the study team

2025-12-10

Who can join

Age: 21 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Provision of a signed and dated written ICF prior to any mandatory study-specific procedures, sampling, and analyses
• Age ≥ 21 years at the time of screening
• Histologically-confirmed, unresectable advanced or metastatic carcinoma of the biliary tract including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder carcinoma
• No prior systemic therapy for locally advanced, metastatic, or recurrent BTC (prior adjuvant capecitabine therapy is allowed as long as last treatment was ≥ 1 month before enrollment)
• An ECOG performance status of 0-2 at enrollment
• At least 1 lesion that qualifies as a RECIST version 1.1 target lesion in the abdomen or pelvis that is amenable to SFRT on contrast enhanced CT or MRI
• No prior exposure to gemcitabine or platinum-based chemotherapy
• No prior exposure to anti-PD1 or anti-PDL1 antibodies
• Adequate organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• ANC ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Serum bilirubin ≤ 2.5 x upper limit of normal (ULN)
• Alanine aminotransferase and aspartate aminotransferase ≤ 3 x ULN
• Measured creatinine clearance > 50 mL/min or calculated creatinine clearance > 50 mL/min as determined by Cockcroft-Gault (using actual body weight)
• Life expectancy of at least 12 weeks at the time of screening
• Body weight >30 kg
• Participants must provide a tumor biopsy taken within 3 years prior to screening
• Baseline vitals: heart rate of ≤ 90bpm, systolic blood pressure of 140-100mmHg and diastolic of 90-60mmHg

You may not qualify if…

• Ampullary carcinoma
• History of allogeneic organ transplantation
• Prior history of radiation to the proposed treatment site
• Active or prior documented autoimmune or inflammatory disorders with the following exceptions:
• Participants with vitiligo or alopecia
• Participants with hypothyroidism stable on hormone replacement
• Any chronic skin condition that does not requires systemic therapy
• Participants without an active disease in the last 5 years may be included but only after consultation with the study physician
• Participants with celiac disease controlled by diet alone
• Known history or evidence of active, non-infectious pneumonitis
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring adverse events, or compromise the ability of the participant to give written informed consent
• Participants with documented myocardial infarction or cerebrovascular accident within 6 months prior to enrollment
• History of another primary malignancy, except for:
• Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of investigational product and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• History of leptomeningeal carcinomatosis
• Active infection including tuberculosis, hepatitis B or hepatitis C. Participants with a past or resolved hepatitis B infection or participants positive for hepatitis C antibody with negative hepatitis C virus RNA on polymerase chain reaction are eligible to enroll. Participants with HIV with undetectable viral load and CD4 cell count ≥200 cells/mm3 are eligible to enroll
• Any unresolved toxicity per CTCAE version 5.0 grade ≥2 from a previous anticancer therapy, except for alopecia, vitiligo and the laboratory values defined in the inclusion criteria.
• Participants with grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
• Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician
• Untreated brain metastases or spinal cord compression. Participants with suspected brain metastases at screening should have an MRI (preferred) or CT scan, each preferably with IV contrast of the brain prior to study entry
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
• Any concurrent chemotherapy, investigational product, biologic or hormonal therapy for cancer treatment
• Concurrent use of hormonal therapy for non-cancer related conditions is acceptable

Where it is running

• Maryland Proton Treatment Center — Baltimore, Maryland, United States (enrolling)
• University of Maryland Greenebaum Cancer Center — Baltimore, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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