Stereotactic Body Radiotherapy (SBRT) Followed by Immunotherapy in Liver Cancer

NCT03203304 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IRB17-0578
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

External beam photon stereotactic body radiotherapy (SBRT) using a linear accelerator to a total dose of 40 Gy in 5 fractions delivered once daily with at least 48 hours between each fraction. SBRT treatment will be completed within a 21-day window. Starting within 14 days after completion of SBRT, intravenous nivolumab 240 mg will be given every 2 weeks as monotherapy or in combination with ipilimumab 1 mg/kg IV every 6 weeks.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; nivolumab; ipilimumab; stereotactic body radiotherapy; SBRT

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events

  To determine the safety and tolerability of SBRT followed by nivolumab or ipilimumab with nivolumab for hepatocellular carcinoma by establishing the rates of toxicity that occur within 6 months from start of SBRT by analyzing the number of patients with adverse events.

  3 years

Secondary Outcomes (6)

• Overall response rate

  3 years

• Number of long-term adverse events

  from date of randomization until the date of last documented adverse event or date of death from any cause, whichever comes first, up to 100 months

• Time to progression free survival

  from date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, up to 100 months

• Time of overall survival

  from date of randomization until the date of death from any cause, whichever comes first, up to 100 months

• Rate of disease control

  from date of randomization until the date of death from any cause, whichever comes first, up to 100 months

Study Arms (2)

Nivolumab

EXPERIMENTAL

Patients will be randomly placed in either of the two arms. All patients will undergo CT simulation and stereotactic body radiotherapy (SBRT). SBRT treatment will be completed within a 21-day window. After the final fraction of SBRT, patients will receive treatment with nivolumab 240 mg will be initiated within 14 days. Patients will receive nivolumab infusions once every 2 weeks. Patients will be restaged after every 4 doses of nivolumab (every 8 weeks). Treatment beyond progression is allowed as per irRC evaluation.

Drug: Nivolumab

Nivolumab and ipilimumab

EXPERIMENTAL

Patients will be randomly placed in either of the two arms. All patients will undergo CT simulation and stereotactic body radiotherapy (SBRT). SBRT treatment will be completed within a 21-day window. After the final fraction of SBRT, treatment with nivolumab and ipilimumab will be initiated within 14 days. Patients will be restaged after every 4 doses of nivolumab (every 8 weeks). Treatment beyond progression will be allowed as per irRC evaluation. Patients will receive nivolumab infusions once every 2 weeks and ipilimumab infusions once every 6 weeks.

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

240mg every two weeks by IV infusion

Also known as: Opdivo

Nivolumab; Nivolumab and ipilimumab

Ipilimumab DRUG

1mg/kg every six weeks by IV infusion

Also known as: Yervoy

Nivolumab and ipilimumab

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have ECOG performance status 0-1.
• Pretreatment CT chest /abdomen /pelvis within 28 days of protocol enrollment.
• Pathologic diagnosis of hepatocellular carcinoma (including fibrolamellar variants and biphenotypic tumors with an HCC component).
• Child Pugh Class A (score = 5 or 6)cirrhosis (assessed within 14 days of SBRT)
• Deemed ineligible for curative intent therapy with surgical resection or liver transplantation.
• Patients with diffuse/multifocal liver involvement are eligible.
• Patients with extrahepatic disease are eligible.
• Prior systemic therapies for HCC are allowed but not required.
• Must have at least one intrahepatic lesion amenable to SBRT.
• Prior transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) allowed, however, patient must have separate intrahepatic lesion amenable to SBRT and biopsy.
• Intrahepatic lesion amenable to pre and post SBRT biopsies, unless the investigator determines that the tumor biopsies would be unsafe.
• Have measurable disease based on RECIST 1.1.
• Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 14 days of treatment initiation.

You may not qualify if:

• Prior external beam radiation therapy to the liver (defined as \> 1 Gy).
• Prior yttrium-90 radioembolization treatment.
• Patients with HBV viral load \> 100 IU/mL (antiviral therapy per local practice is required).
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose of \>10 mg prednisone daily or equivalent at time of first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to nivolumab or ipilimumab or any of its excipients.
• Has had prior anticancer therapy within 4 weeks of study Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has a known additional malignancy that is progressing or requires active treatment.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with allografts (including liver transplants) are not eligible for this protocol.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Chih-Yi Liao, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: June 29, 2017
• Study Start: August 25, 2017
• Primary Completion: March 13, 2019
• Study Completion: March 13, 2019
• Last Updated: June 10, 2021

Record last verified: 2021-06

Locations

US (3)