A Pilot Study of Chemoimmunotherapy Combined with Hyperthermia and Spatially-Fractionated Radiotherapy in Advanced Biliary Tract Cancer
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.
• 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