Trial Title:
Chemoimmunotherapy Combined With Hyperthermia and Spatially-Fractionated Radiotherapy in Advanced Biliary Tract Cancer
NCT ID:
NCT06546969
Condition:
Biliary Tract Cancer
Conditions: Official terms:
Biliary Tract Neoplasms
Hyperthermia
Fever
Gemcitabine
Durvalumab
Conditions: Keywords:
Chemoimmunotherapy
Spatially Fractionated Radiation Therapy
Deep Hyperthermia
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
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.
Arm group label:
Chemoimmunotherapy + SFRT + Deep Hyperthermia
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
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.
Arm group label:
Chemoimmunotherapy + SFRT + Deep Hyperthermia
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
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.
Arm group label:
Chemoimmunotherapy + SFRT + Deep Hyperthermia
Intervention type:
Radiation
Intervention name:
Spatially Fractionated RT
Description:
Administered to 1 measurable lesion on cycle 2-day 1
Arm group label:
Chemoimmunotherapy + SFRT + Deep Hyperthermia
Intervention type:
Device
Intervention name:
Deep Hyperthermia
Description:
Deep hyperthermia alone will be delivered to the same lesion on cycle 3-day 1 and cycle
4-day 1
Arm group label:
Chemoimmunotherapy + SFRT + Deep Hyperthermia
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.
Criteria for 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
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
11. 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
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
Gender:
All
Minimum age:
21 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Maryland Proton Treatment Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Contact:
Last name:
Caitlin Eggleston
Phone:
410-369-7586
Email:
caitlineggleston@umm.edu
Facility:
Name:
University of Maryland Greenebaum Cancer Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Start date:
October 2024
Completion date:
December 2028
Lead sponsor:
Agency:
University of Maryland, Baltimore
Agency class:
Other
Source:
University of Maryland, Baltimore
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06546969
