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

NCT06546969 | Recruiting Phase 1 DMC FDA Device

• 1 other identifier: HP-00109947
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Biliary Tract Cancer; Cholangiocarcinoma

Keywords

Chemoimmunotherapy; Spatially Fractionated Radiation Therapy; Deep Hyperthermia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Radiographic Response Rate

  16 weeks from start of treatment

Other Outcomes (3)

• Measure absolute number of immune cell subsets

  1 year post completion of accrual

• Measure distribution of immune cell subsets

  1 year post completion of accrual

• Measure activation status of immune cell subsets

  1 year post completion of accrual

Study Arms (1)

Chemoimmunotherapy + SFRT + Deep Hyperthermia

EXPERIMENTAL

1. Gemcitabine 1000mg/m2 via intravenous infusion on days 1 and 8 of every 21-day cycle for up to 8 cycles 2. Cisplatin 25mg/m2 via intravenous infusion on days 1 and 8 of every 21-day cycle for up to 8 cycles 3. Durvalumab 1500mg via intravenous infusion on day 1 of every 21-day cycle for up to 8 cycles 4. Deep hyperthermia and spatially-fractionated radiotherapy will be administered to 1 measurable lesion on cycle 2-day 1 and deep hyperthermia alone will be delivered to the same lesion on cycle 3-day 1 and cycle 4-day 1

Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Radiation: Spatially Fractionated RT; Device: Deep Hyperthermia

Interventions

Gemcitabine DRUG

1000mg/m2 via intravenous infusion on days 1 and 8 of every 21-day cycle for up to 8 cycles. After the 16 weeks of trial participation, participants will continue chemoimmunotherapy per standard of care.

Chemoimmunotherapy + SFRT + Deep Hyperthermia

Cisplatin DRUG

25mg/m2 via intravenous infusion on days 1 and 8 of every 21-day cycle for up to 8 cycles. After the 16 weeks of trial participation, participants will continue chemoimmunotherapy per standard of care.

Chemoimmunotherapy + SFRT + Deep Hyperthermia

Durvalumab DRUG

1500mg via intravenous infusion on day 1 of every 21-day cycle for up to 8 cycles. After the 16 weeks of trial participation, participants will continue chemoimmunotherapy per standard of care.

Chemoimmunotherapy + SFRT + Deep Hyperthermia

Spatially Fractionated RT RADIATION

Administered to 1 measurable lesion on cycle 2-day 1

Chemoimmunotherapy + SFRT + Deep Hyperthermia

Deep Hyperthermia DEVICE

Deep hyperthermia alone will be delivered to the same lesion on cycle 3-day 1 and cycle 4-day 1

Chemoimmunotherapy + SFRT + Deep Hyperthermia

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (2)

Maryland Proton Treatment Center

Baltimore, Maryland, 21201, United States

RECRUITING

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma

Interventions

Gemcitabine; Cisplatin; durvalumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Jason Molitoris, MD, PhD

  University of Maryland Medical Center / Maryland Proton Treatment Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason Molitoris, MD, PhD

CONTACT

410-328-6080; JMolitoris@som.umaryland.edu

Caitlin Eggleston

CONTACT

410-328-7586; caitlineggleston@umm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 9, 2024
• Study Start: October 29, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)