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

NCT ID: NCT06546969

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-29
• Study Completion Date: 2028-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemoimmunotherapy + SFRT + Deep Hyperthermia

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

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: 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.

Cisplatin

Intervention Type: 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.

Durvalumab

Intervention Type: 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.

Spatially Fractionated RT

Intervention Type: RADIATION

Administered to 1 measurable lesion on cycle 2-day 1

Deep Hyperthermia

Intervention Type: DEVICE

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

Interventions

Gemcitabine

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.

Intervention Type: DRUG

Cisplatin

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.

Intervention Type: DRUG

Durvalumab

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.

Intervention Type: DRUG

Spatially Fractionated RT

Administered to 1 measurable lesion on cycle 2-day 1

Intervention Type: RADIATION

Deep Hyperthermia

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. 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

2. Provision of a signed and dated written ICF prior to any mandatory study-specific procedures, sampling, and analyses

3. Age ≥ 21 years at the time of screening

4. Histologically-confirmed, unresectable advanced or metastatic carcinoma of the biliary tract including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder carcinoma

5. 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)

6. An ECOG performance status of 0-2 at enrollment

7. 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

8. No prior exposure to gemcitabine or platinum-based chemotherapy

9. No prior exposure to anti-PD1 or anti-PDL1 antibodies

10. 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)

11. Life expectancy of at least 12 weeks at the time of screening

12. Body weight >30 kg

13. Participants must provide a tumor biopsy taken within 3 years prior to screening

14. Baseline vitals: heart rate of ≤ 90bpm, systolic blood pressure of 140-100mmHg and diastolic of 90-60mmHg

• 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

12. 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

13. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

14. Any concurrent chemotherapy, investigational product, biologic or hormonal therapy for cancer treatment

• Concurrent use of hormonal therapy for non-cancer related conditions is acceptable

15. Receipt of live attenuated vaccine within 30 days prior to the enrollment

16. Major surgical procedure within 28 days prior to enrollment.

17. Prior locoregional therapy with radioembolization

18. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab with the following exceptions:

• Intranasal, inhaled, or topical steroids or local steroid injection
• Systemic corticosteroids at physiologic doses not to exceed 10mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions

19. Participation in another clinical study with an investigational product administered in the last 3 months

20. Concurrent enrollment in another clinical study, unless it is an observational clinical study or during the follow-up period of an interventional study

21. Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to use effective birth control from screening to 180 days after the last dose of gemcitabine/cisplatin or 90 days after the last dose of durvalumab

22. Judgement by the investigator that the participant should not participate in the study if they are unlikely to comply with study procedures, restrictions, and requirements

23. Participants on anti-arrhythmic medication unless they are deemed fit for HT by a consultant cardiologist and there is no increased risk to the patient from HT because of the arrhythmia in the opinion of the treating physician

24. Severe COPD with FEV1 < 50% of expected

25. Participants whose right-to-left pelvic/abdominal dimension is > 49 cm

26. Participants with incorporated metallic implants such as metallic stents, pacemakers or defibrillators, and orthopedic rods and plates of dimensions > 1000/frequency (MHz) aa. Participants who are under any therapy, which by virtue of direct pharmacological action or heat interaction, could influence the intended effects of HT or mask its side effects

Exclusion Criteria

1. Ampullary carcinoma

2. History of allogeneic organ transplantation

3. Prior history of radiation to the proposed treatment site

4. 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

5. Known history or evidence of active, non-infectious pneumonitis

6. 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

7. Participants with documented myocardial infarction or cerebrovascular accident within 6 months prior to enrollment

8. 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

9. History of leptomeningeal carcinomatosis

10. 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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Jason Molitoris, MD PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason Molitoris, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland Medical Center / Maryland Proton Treatment Center

Locations

Maryland Proton Treatment Center

Baltimore, Maryland, United States

Site Status: RECRUITING

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jason Molitoris, MD, PhD

Role: CONTACT

JMolitoris@som.umaryland.edu

410-328-6080

Caitlin Eggleston

Role: CONTACT

caitlineggleston@umm.edu

410-328-7586

Facility Contacts

Caitlin Eggleston

Role: primary

caitlineggleston@umm.edu

410-369-7586

Caitlin Eggleston, BS

Role: primary

caitlineggleston@umm.edu

4103287586

Other Identifiers

HP-00109947

Identifier Type: -

Identifier Source: org_study_id