RECRUITING

Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer

Conditions

Hepatocellular Carcinoma Biliary Tract Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This research study is studying a combination of drugs as a possible treatment for Hepatocellular Carcinoma or Biliary Tract Cancer. The interventions involved in this study are: * Durvalumab * Tremelimumab * Radiation Therapy

Official Title

A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer

Quick Facts

Study Start:2018-05-14

Study Completion:2026-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03482102

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically or cytologically confirmed hepatocellular carcinoma or biliary tract cancer * Locally advanced/unresectable or metastatic disease * Age ≥ 18 years at time of study entry * ECOG Performance Status ≤ 1 * One previously unirradiated lesion amenable to 8 Gy x 3 radiotherapy based on dosimetric organ tolerance AND another unirradiated measurable lesion (per irRECIST) outside of the radiation field * Immunotherapy-naïve * Progressed on, be intolerant of, or refused sorafenib \[for HCC\], second line treatment and beyond for cholangiocarcinoma or gemcitabine-based chemotherapy for biliary tract cancer * The benefits of sorafenib have been discussed with the patient and the patient has refused treatment with sorafenib. * Viral status (Hepatitis B and C) must be known. All HBV-positive patients must be on antiviral medication for viral suppression. * Patients with concomitant HBV infection must have a confirmed diagnosis of HBV characterized by the presence of hepatitis B core antibodies, and be sufficiently suppressed with active antiviral treatment (per local institutional practice) prior to enrollment to ensure adequate viral suppression (HBV deoxyribonucleic acid \[DNA\] \<2000 IU/mL). * Patients with concomitant HCV infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV ribonucleic acid (RNA or anti-HCV antibody upon enrollment. * Body weight ≥ 30 kg * Child-Pugh Score of A. A score of B7 is allowed without severe ascites or without hepatic encephalopathy. * Adequate organ and marrow function, defined as: * Hemoglobin ≥ 9 g/dL * ANC ≥ 1.5 x 10\^9/L * Platelet count ≥75×109/L * Serum bilirubin ≤2.0× the upper limit of normal (ULN). * ALT and AST ≤ 3 x institutional ULN * Albumin \> 2.8 g/dL * INR \< 2.0 * Calculated creatinine clearance \> 40 mL/min as determined by Cockcroft-Gault (using actual body weight) * Males: * Females: * Ability to understand and the willingness to sign a written informed consent document * Female subjects must be either of non-reproductive potential (i.e., post-menopausal by history: ≥ 50 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry. * Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations with follow up	* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC * Prior irradiation to the planned radiation target lesion * Prior immunotherapy including but not limited to anti-CTLA4, including tremelimumab anti-PD-1, and anti-PD-L1, including durvalumab * Concurrent enrollment in another study unless it is an observational (e.g. non-interventional) study * Received live attenuated vaccines within 30 days of first dose * Mean QT interval corrected for heart rate (QTc) ≥ 470 ms using Fredericia's Correction * History of primary immunodeficiency * History of solid organ transplantation * Active or prior documented autoimmune disease within the past 2 years (NOTE: The following are exceptions to this criterion: Participants with vitiligo or alopecia; Participants with hypothyroidism (e.g. following Hashimoto syndrome) who are stable on hormone replacement; Participants with celiac disease controlled by diet alone: Participants with Grave's disease, or any chronic skin condition not requiring systemic treatment. Participants without active disease in the last 5 years may be included but only after consultation with the study physician.) * Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis) * Prior other malignancy within 2 years (except for in situ disease, which is permissible) * History of hypersensitivity to durvalumab, tremelimumab or any excipient * History of (non-infectious) pneumonitis that required steroids; or evidence of interstitial lung disease or 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, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent * Current or prior use of immunosuppressive medication within 28 days before the first dose of treatment on this protocol, with the exceptions of * Intranasal and inhaled corticosteroids * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent * Premedication for hypersensitivity reactions (e.g. to CT contrast for scans) * Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Subjects with uncontrolled seizures * Female subjects who are pregnant or breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period. * 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 * Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. * Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. * Brain metastases or spinal cord compression. 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 or brain metastases or spinal cord compression unless the patient is stable (asymptomatic; no evidence of new or emerging brain metastases; and stable and off steroids and anti-convulsants for at least 14-28 days prior to start of study treatment). Following radiotherapy and/or surgery of the brain metastases patients must wait 4 weeks following the intervention to confirm stability.

Inclusion Criteria

Exclusion Criteria

* Histologically or cytologically confirmed hepatocellular carcinoma or biliary tract cancer
* Locally advanced/unresectable or metastatic disease
* Age ≥ 18 years at time of study entry
* ECOG Performance Status ≤ 1
* One previously unirradiated lesion amenable to 8 Gy x 3 radiotherapy based on dosimetric organ tolerance AND another unirradiated measurable lesion (per irRECIST) outside of the radiation field
* Immunotherapy-naïve
* Progressed on, be intolerant of, or refused sorafenib \[for HCC\], second line treatment and beyond for cholangiocarcinoma or gemcitabine-based chemotherapy for biliary tract cancer
* The benefits of sorafenib have been discussed with the patient and the patient has refused treatment with sorafenib.
* Viral status (Hepatitis B and C) must be known. All HBV-positive patients must be on antiviral medication for viral suppression.
* Patients with concomitant HBV infection must have a confirmed diagnosis of HBV characterized by the presence of hepatitis B core antibodies, and be sufficiently suppressed with active antiviral treatment (per local institutional practice) prior to enrollment to ensure adequate viral suppression (HBV deoxyribonucleic acid \[DNA\] \<2000 IU/mL).
* Patients with concomitant HCV infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV ribonucleic acid (RNA or anti-HCV antibody upon enrollment.
* Body weight ≥ 30 kg
* Child-Pugh Score of A. A score of B7 is allowed without severe ascites or without hepatic encephalopathy.
* Adequate organ and marrow function, defined as:
* Hemoglobin ≥ 9 g/dL
* ANC ≥ 1.5 x 10\^9/L
* Platelet count ≥75×109/L
* Serum bilirubin ≤2.0× the upper limit of normal (ULN).
* ALT and AST ≤ 3 x institutional ULN
* Albumin \> 2.8 g/dL
* INR \< 2.0
* Calculated creatinine clearance \> 40 mL/min as determined by Cockcroft-Gault (using actual body weight)
* Males:
* Females:
* Ability to understand and the willingness to sign a written informed consent document
* Female subjects must be either of non-reproductive potential (i.e., post-menopausal by history: ≥ 50 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
* Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations with follow up

* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
* Prior irradiation to the planned radiation target lesion
* Prior immunotherapy including but not limited to anti-CTLA4, including tremelimumab anti-PD-1, and anti-PD-L1, including durvalumab
* Concurrent enrollment in another study unless it is an observational (e.g. non-interventional) study
* Received live attenuated vaccines within 30 days of first dose
* Mean QT interval corrected for heart rate (QTc) ≥ 470 ms using Fredericia's Correction
* History of primary immunodeficiency
* History of solid organ transplantation
* Active or prior documented autoimmune disease within the past 2 years (NOTE: The following are exceptions to this criterion: Participants with vitiligo or alopecia; Participants with hypothyroidism (e.g. following Hashimoto syndrome) who are stable on hormone replacement; Participants with celiac disease controlled by diet alone: Participants with Grave's disease, or any chronic skin condition not requiring systemic treatment. Participants without active disease in the last 5 years may be included but only after consultation with the study physician.)
* Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)
* Prior other malignancy within 2 years (except for in situ disease, which is permissible)
* History of hypersensitivity to durvalumab, tremelimumab or any excipient
* History of (non-infectious) pneumonitis that required steroids; or evidence of interstitial lung disease or 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, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
* Current or prior use of immunosuppressive medication within 28 days before the first dose of treatment on this protocol, with the exceptions of
* Intranasal and inhaled corticosteroids
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
* Premedication for hypersensitivity reactions (e.g. to CT contrast for scans)
* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
* Subjects with uncontrolled seizures
* Female subjects who are pregnant or breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.
* 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
* Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
* Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
* Brain metastases or spinal cord compression. 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 or brain metastases or spinal cord compression unless the patient is stable (asymptomatic; no evidence of new or emerging brain metastases; and stable and off steroids and anti-convulsants for at least 14-28 days prior to start of study treatment). Following radiotherapy and/or surgery of the brain metastases patients must wait 4 weeks following the intervention to confirm stability.

Contacts and Locations

Study Contact

Theodore Hong, MD

CONTACT

617-726-6050

TSHONG1@mgh.harvard.edu

Principal Investigator

Theodore S. Hong, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Massachusetts General Hospital

Boston, Massachusetts, 02214

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Collaborators and Investigators

Sponsor: Massachusetts General Hospital

Theodore S. Hong, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-05-14

Study Completion Date2026-10

Study Record Updates

Study Start Date2018-05-14

Study Completion Date2026-10

Terms related to this study

Keywords Provided by Researchers

Hepatocellular Carcinoma
Biliary Tract Cancer

Additional Relevant MeSH Terms

Hepatocellular Carcinoma
Biliary Tract Cancer