HYPERION CCA

ClinicalTrials.gov Identifier

NCT06858735

Institution Name

MD Anderson Cancer Center

Full Institution Address

1220 Holcombe Blvd Houston TX 77030 United States

Institution Phone

713-792-7090

Institution Website

https://clinicaltrials.gov/study/NCT06858735

Principal Investigator

Eugene J. Koay

Principal Investigator Phone

713-563-2381

Principal Investigator Email

ekoay@mdanderson.org

Study Coordinator

Kristi Villata

Study Coordinator Phone

713-794-1714

Study Coordinator Email

KMVillalta@mdanderson.org

Study Overview

Intrahepatic cholangiocarcinoma remains a highly lethal disease despite advances in drug therapies in recent years. The majority of patients succumb to the disease due to liver failure from the cancer causing problems with the bile duct system or the blood vessels supplying oxygen and nutrients to the liver. Current clinical guidelines do not include radiation therapy as a clear front line option for patients with unresectable or metastatic intrahepatic cholangiocarcinoma, even though there are retrospective and limited prospective data supporting radiation therapy as a method to reduce the risk of liver failure and potentially prolong the lives of patients. Randomized studies are needed to demonstrate value of radiation therapy, and HYPERION CCA will compare the overall survival times of patients who receive standard of care chemoimmunotherapy (gemcitabine/cisplatin/durvalumab) with or without radiation therapy for patients with intrahepatic cholangiocarcinoma.

Enrollment Information

Enrollment goal of 126 patients

Study Start Date

2025-08-25

Study End Date

2028-08-31

Study Purpose

The purpose of this study is to prospectively demonstrate the value of radiation therapy in combination with chemoimmunotherapy, as compared to chemoimmunotherapy alone, for patients with intrahepatic cholangiocarcinoma that is not surgically resectable and/or has spread outside of the liver. The study will compare the overall survival times between patients who are randomly assigned to one of the two treatment arms. The randomization will be in a 2:1 ratio (chemoimmunotherapy+radiation therapy vs. chemoimmunotherapy alone). Patients who are randomized to chemoimmunotherapy alone will be allowed to receive radiation therapy later on. Other objectives of the study are to measure the time to progression in the two treatment arms, the quality of life of patients in the two treatment arms, and correlate the outcomes of the patients with blood/imaging/tissue biomarkers.

Inclusion Criteria

1. Patients older than the age of 18 years old at the time of study entry. 2. Patients with a body mass greater than 30 kg. 3. Patients with a pathological diagnosis or radiographic evidence of intrahepatic cholangiocarcinoma and at least one intrahepatic tumor measuring 3 cm in greatest dimension 4. Patients must have pathological or radiographic evidence of either: a. locally advanced unresectable iCCA – a multidisciplinary discussion should be documented for patients who have liver confined disease, confirming that the patient is not resectable. b. extrahepatic metastasis at the time of enrollment – allowable extrahepatic metastases may include disease in non-regional lymph nodes (note that metastatic involvement of regional lymph nodes in the hilum of the liver alone do not qualify as M1 disease), lung, and/or bone. 5. Patients should receive at least 4 cycles of systemic therapy with gemcitabine/cisplatin or other gemcitabine-based combinations as per standard of care with durvalumab. If one of the drugs (gemcitabine/cisplatin/durvalumab) was held at any point for medical reasons during the initial 4 cycles, the patient is still eligible as long as the treating team agrees about the ability of the patient to continue systemic therapy. 6. Patients must be appropriate candidates for radiation therapy with adequate liver function, at the discretion of the treating physician. 7. A patient may pre-register at any time before cycle 4 of systemic therapy. To be eligible to pre-register for the trial, they must meet all other inclusion and exclusion criteria, except criteria number 5 regarding the number of cycles of systemic therapy.Pre-registration is not required to enroll. 8. Have adequate organ function for study treatments. 9. Must have a life expectancy of at least 12 weeks 10. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization 11. 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. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocolrelated procedures, including screening evaluations. 12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria

1. Participation in another clinical study with an investigational product during the last 1 month. 2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 3. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria a. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. b. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. 4. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment other than stated in the inclusion criteria. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 5. Major surgical procedure (as defined by the treating physician) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 6. History of allogenic organ transplantation. 7. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following is an exception to this criterion: a. Patients with asymptomatic or controlled autoimmune disease may be permitted if treating physicians agree that immunotherapy is safe. 8. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 9. History of leptomeningeal carcinomatosis 10. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry. Patients with brain metastasis or metastases confirmed on imaging will be excluded. 11. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) 12. History of active primary immunodeficiency 13. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of antiHBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Required Tests Prior to Study

Blood tests, an EKG and imaging must be done and be within the study criteria within 28 days of study enrollment.

Potential Side Effects

The radiation therapy can cause short and long term side effects, and the degree of side effects depends on the patient and what needs to be treated with radiation (for example, the liver tumor alone, or the liver tumor plus nearby lymph nodes). Generally, radiation therapy causes short term nausea and fatigue. Some patients may have vomiting due to the nausea. The radiation therapy can also reduce blood counts, leading to an increased risk of bleeding and infection. A small number of patients may need blood transfusion(s). Longer term side effects include scar tissue in the field of radiation that can lead to problems in the intestines and liver. The chances of severe side effects in the short term and long term with the modern radiation techniques are all low, and the safety of modern radiation therapy for the treatment of intrahepatic cholangiocarcinoma have been demonstrated in multiple studies. Chemoimmunotherapy is the standard of care for patients with intrahepatic cholangiocarcinoma, and also carries risks. Patients can experience nausea, vomiting, fatigue, and organ dysfunction as a consequence of the treatments.

Financial Assistance Available

No

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