Y90 Radiation Segmentectomy vs SBRT for HCC (SBRT vs Y90)

• ClinicalTrials.gov Identifier: NCT04235660
• Recruitment Status: Recruiting
• First Posted: January 22, 2020
• Last Update Posted: August 30, 2021
• Sponsor: Indiana University
• Information provided by (Responsible Party): Paul Michael Haste, MD, Indiana University

Study Description

Brief Summary:

The proposed study is a single site, prospective, randomized pilot study to assess the feasibility of recruitment of patients into a trial evaluating the efficacy and tolerability of selective transarterial Y90 radioembolization (radiation segmentectomy) versus stereotactic body radiation therapy (SBRT) for solitary early stage (≤ 3cm) hepatocellular carcinoma (HCC).

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma (HCC)	Radiation: Yttrium-90 Radiation Segmentectomy; Radiation: Stereotactic Body Radiation Therapy	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Radiologist assessing response will be blinded to the treatment type
• Primary Purpose: Treatment
• Official Title: Yttrium-90 Radiation Segmentectomy Versus Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Early Stage Hepatocellular Carcinoma (HCC): A Pilot Study
• Actual Study Start Date: July 22, 2020
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Yttrium-90 Radiation Segmentectomy	Radiation: Yttrium-90 Radiation Segmentectomy; This therapy arm involves two separate steps, a planning/mapping arteriogram and a therapy delivery. The planning arteriogram will be performed to confirm arterial anatomy is acceptable for RS (≤2 segment delivery) and that lung shunting is not too high to preclude treatment with RS. Once confirmed, patients will return for RS (within 45 days of mapping). Dose will be calculated based off the desired treatment volume using pre-treatment cross-sectional imaging. The desired segmental dose will be calculated to be ≥ 200Gy. RS will be performed by one of three separate interventional radiologists with experience in radioembolization. Actual administered activity and location of dose administration will be recorded.
Active Comparator: Stereotactic Body Radiation Therapy	Radiation: Stereotactic Body Radiation Therapy; SBRT will be delivered with linear accelerator-based photon beams with either fixed angle non- coplanar fields or dynamic arcs. An internal target volume (ITV) will be generated to account for tumor movement during breathing cycle. Finally, a planning target volume (PTV) will be an expansion of 3- 5mm from the ITV. For Child Pugh A patients, prescription dose will either be 5000cGy in 5 fractions delivered every other day or 4800cGy in 3 fractions delivered twice weekly. For Child Pugh B patients, prescription dose of 4000cGy in 5 fractions delivered every other day. Inverse planning will be used. 95% of the PTV or more will receive at least 100% of the prescription dose. Normal tissue dose constraints for each dose level will be respected with acceptable deviations permitted as outlined in appendix VII. Patients will be seen at least once per week by a clinician to grade toxicities, with on- treatment labs (CBC, CMP, INR) each week.

Outcome Measures

Primary Outcome Measures :

1. Feasibility of Recruitment (Recruitment Rate) [ Time Frame: 24 months ]
   Feasibility of recruitment will be measured by evaluating the proportion of patients enrolled versus those approached for the study after they have been determined to be a candidate.

Secondary Outcome Measures :

1. Proportion of patients with any toxicities [ Time Frame: 24 months ]
   the proportion of patients with any toxicities (≥ grade 4) using CTCAE between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC).
2. Mean change in hepatobiliary function [ Time Frame: 24 months ]
   the mean change in hepatobiliary function, as measured 3 months after treatment using a functional HIDA scan, between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC).
3. Mean change in Functional Assessment of Cancer Therapy- General (FACT-G) score [ Time Frame: 6 months ]
   the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Functional Assessment of Cancer Therapy- General (FACT-G) and
4. Mean change in Comprehensive Score for Financial Toxicity [ Time Frame: 6 months ]
   the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Comprehensive Score for Financial Toxicity (COST)
5. Disease-free survival (DFS) rates of RS and SBRT [ Time Frame: 24 months ]
   the disease-free survival (DFS) rates of RS and SBRT at 2 years using mRECIST on CT or MR for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC).
6. Time-to-secondary treatment (TTST) between RS and SBRT [ Time Frame: 24 months ]
   time-to-secondary treatment (TTST) between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) up to 2 years after initial treatment.
7. Objective response rate [ Time Frame: 6 months ]
   the objective response rate (ORR) of radiation segmentectomy (RS) and stereotactic body radiation therapy (SBRT) as measured at 6 months using mRECIST (appendix IV) for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) to better allow for an appropriately powered trial evaluating the efficacy of these treatments.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Ability to provide written informed consent and HIPAA authorization
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged ≥ 18 years at time of informed consent
• Solitary HCC (≤3 cm) diagnosed by imaging (LI-RADS 4-5) or histology
• Childs-Pugh score ≤ 7
• ECOG performance status 0-1
• Tumor location/characteristics eligible for either SBRT or Y90 therapy as deemed by local tumor board

• Adequate organ function defined as:

  1. serum bilirubin < 4.0 mg/dL ,
  2. albumin > 2 g/dL

Exclusion Criteria:

• Any prior locoregional therapy to the target tumor
• Any prior radiation therapy to the liver

• Pregnancy or lactation: Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:

  i. Has undergone a hysterectomy or bilateral oophorectomy; or ii. Has been naturally amenorrheic for at least 24 consecutive months

• Known severe allergic reaction (anaphylaxis) to iodinated contrast
• Coagulopathy (platelets < 50 K/mm3 and/or INR > 2) not correctable by transfusion
• Macrovascular invasion or extrahepatic HCC

Contacts and Locations

Contacts

Contact: Paul Haste, MD; 317-944-5005; phaste@iupui.edu

Locations

United States, Indiana

Indiana University; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Hayley Trussell, RN-BSN 317-963-0305 hktrusse@iu.edu

Principal Investigator: Paul Haste, MD

Sponsors and Collaborators

Indiana University

More Information

• Responsible Party: Paul Michael Haste, MD, Assistant Professor of Clinical Radiology & Imaging Sciences, Indiana University
• ClinicalTrials.gov Identifier: NCT04235660
• Other Study ID Numbers: IU-2001712954
• First Posted: January 22, 2020
• Last Update Posted: August 30, 2021
• Last Verified: August 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

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