Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial Comparing PLA to HIGRT Therapy (PROVE-HCC) (PROVE-HCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03402607
Recruitment Status : Suspended (Administrative hold)
First Posted : January 18, 2018
Last Update Posted : September 3, 2020
Sponsor:
Collaborators:
Durham VA Medical Center
Hunter Holmes McGuire VA Medical Center
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE January 11, 2018
First Posted Date  ICMJE January 18, 2018
Last Update Posted Date September 3, 2020
Actual Study Start Date  ICMJE August 8, 2018
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2018)
Quality of Life (QOL) [ Time Frame: Baseline to one month ]
To compare change in Quality of Life (QOL), as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30) post treatment in patients receiving PLA vs HIGRT.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2018)
  • Quality of Life (QOL) [ Time Frame: Baseline to 3 months ]
    To compare change in Quality of Life (QOL), as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30) post treatment in patients receiving PLA vs HIGRT.
  • Quality of Life (QOL) [ Time Frame: Baseline to 6 months ]
    To compare change in Quality of Life (QOL), as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30) post treatment in patients receiving PLA vs HIGRT.
  • Quality of Life [ Time Frame: Baseline to one month ]
    To compare change in Quality of Life (QOL), as measured by the FACT-Hep questionnaire post treatment in patients receiving PLA vs HIGRT.
  • Acute toxicity: Assess patients for grade 2 or higher acute toxicity as defined by the CTCAE v4.0 [ Time Frame: Up to 90 days post treatment ]
    Assess patients for grade 2 or higher acute toxicity as defined by the CTCAE v4.0
  • Financial toxicity: Assess the total healthcare system cost associated with PLA vs HIGRT [ Time Frame: From time of intervention to 90 days post treatment ]
    Assess the total healthcare system cost associated with PLA vs HIGRT
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial Comparing PLA to HIGRT Therapy (PROVE-HCC)
Official Title  ICMJE Phase II Randomized Trial Comparing Percutaneous Ablation to Hypofractionated Image-Guided Radiation Therapy in Veteran and Non-Veteran, Non-surgical Hepatocellular Carcinoma Patients (PROVE-HCC)
Brief Summary This phase II, randomized trial will compare Quality of Life for patients with Hepatocellular Carcinoma (HCC) who are not surgical candidates or decline surgery and are treated with Percutaneous Local Ablation (PLA) or Hypofractionated Image-Guided Radiation Therapy (HIGRT).
Detailed Description

Primary liver cancer is the world's third most common cause of cancer death. In the United States, unlike other malignancies such as breast, prostate and lung cancer, the incidence of hepatocellular carcinoma (HCC) is increasing. The present gold standard for HCC patients who are medically fit is HCC resection or liver transplant. Surgery is a treatment option for just one third of patients with HCC. For the patients who are not fit for surgery either due to underlying liver disease with associated liver dysfunction or other co-morbidity, a number of non-operative treatments are available for treatment including percutaneous tumor ablation (PLA) or the emerging option of external beam radiotherapy techniques, such as hypo-fractionated image guided radiation therapy (HIGRT) -also known as stereotactic body radiotherapy (SBRT).

Percutaneous local ablation (PLA) selectively targets the tumor with an additional intentional margin of 0.5-1cm of non-cancerous liver tissue and induces tumor cell death, most often via coagulative necrosis. Local application of chemical agents or microwave/radiofrequency waves does not induce systemic effects and is typically performed under real-time ultrasound guidance using local anesthesia and conscious sedation.

Worldwide, RFA is the most commonly used ablation technique. In the US, MWA is quickly becoming the preferred modality of PLA. MWA induces thermal injury through the delivery of electromagnetic energy and the application of rapidly alternating microwave frequency current leads to coagulative necrosis of tissue. Compared with RFA, MWA appears to be more effective for lesions in close proximity to the portal or hepatic veins; heat sink is less of an issue given increased speed with which therapy can be delivered. Additionally, tumor sizes >3cm sometimes can be effectively treated with MWA. A recent meta-analysis comparing RFA to MWA for primary HCC showed they had similar efficacy, although MWA appeared to have improved local tumor control over RFA in the treatment larger tumors.

Advances in radiotherapy simulation, treatment planning and delivery integrated together collectively termed HIGRT or SBRT, have facilitated safe dose escalation to HCC. A number of small, single institutional prospective studies have evaluated the use of HIGRT for treatment of HCC. These experiences suggest that HIGRT is well tolerated and yields excellent local control rates, however, follow up is short and thus many institutions and consensus guidelines favor ablation for early stage HCC patients who are not surgical candidates. The benefits of HIGRT are that it is a non-invasive, outpatient procedure typically delivered in 3-10 fractions. Although no randomized studies have compared HIGRT with other local therapies, in retrospective analysis outcomes appear comparable , warranting further evaluation.

Health-related quality of life (QOL) for patients with HCC is important. QOL targets are important post-treatment metrics; previous studies have shown that both pre-treatment QOL and post-treatment QOL have been associated with overall survival in various cancers. While both PLA and SBRT can ablate tumors, they do have known impacts on patients' QOL. QOL has recently been reported as a clinically important target in patients treated with HIGRT for HCC.

Patients who are potentially eligible for study enrollment will be identified by their treating physician. Ninety patients will be randomized with equal allocation to the two arms. . Randomization will be stratified by whether the baseline QOL score is < 60 or ≥ 60, where QOL is measured by the QLQ-C30 scale. The primary outcome is the change in QOL from baseline to 1 month. The investigators anticipate that approximately 10% of the accrued patients will withdraw before 1 month, leaving 80 evaluable patients to be used in the statistical analyses.

The general linear model will be used to test for an arm effect (in patients receiving PLA vs HIGRT) by regressing change across time in QOL on arm, controlling for the baseline value of QOL and the Child Pugh score. To calculate the power of the arm effect (in patients receiving PLA vs HIGRT) on change in QOL, the investigators first note that the standard deviation of a normally distributed change score (SDC) depends upon the SD of the pre-score, the SD of the post-score, and the Pearson correlation (ρ) between the two scores. If the SD's of the pre-score and the post-score are assumed equal and the correlation between them is 0.50, then SDC = SD. For purposes of the power calculation the investigators assume that SD=10 and ρ = 0.5; therefore SDC= 10. Assuming 40 evaluable patients per arm, the two-sample t-test (1-sided alpha = 0.10) of an arm difference in change across time in QoL has power 0.82 when the true arm difference in change score is 5 (i.e., 50% of SDC). An arm difference of 50% of a standard deviation of an outcome variable is generally considered to be a "medium"-sized effect. In order to have 80 evaluable patients, 90 patients will be accrued (assuming drop out prior to the 1 month EOTRC QOL-C30 questionnaire).

Patients will be on study therapy for approximately 6 months. The end of study participation will be at the completion of the 6 month survey, approximately 180 days post treatment (+/- 30 days). Thereafter patients will continue to be followed by the treating physician as per standard of care for follow up care and long-term follow up information will continue to be collected.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE
  • Procedure: Percutaneous Local Abalation
    Microwave Ablation (MWA) is a form of percutaneous localized ablation using thermal ablation techniques to treat cancer via direct coagulative necrosis. Microwaves can generate high temperatures in a short period of time; MWA has the potential to improve treatment efficacy over radiofrequency ablation as it can be used to treat larger lesions and has less susceptibility to heat-sink due to vessel proximity. MWA uses electromagnetic waves (300 MHz to 300 GHz) to produce oscillation of polar molecules within tissue; this generates tissue necrosis through frictional heating. For HCC, one or more microwave antennae are inserted into the liver, usually under the guidance of ultrasonography or computed tomography (CT). Frequency and length of treatment is determined on a case by case basis depending on tumor size and proximity to vessels or other organs at risk.
    Other Name: Microwave Abalation (MWA)
  • Radiation: Hypofractionated Image Guided Radaition Therapy
    HIGRT represents the only non-invasive curative modality in the management of HCC. HCC patients typically have a host of other medical comorbidities complicated by underlying liver dysfunction that makes the implementation of liver-directed therapy challenging. Presently HIGRT is typically offered only after alternative surgical (transplantation/hepatectomy) and non-operative approaches (PLA/embolization) have been exhausted.
    Other Name: HIGRT
Study Arms  ICMJE
  • Active Comparator: Percutaneous Local Abalation (PLA)
    A PLA procedure uses high-energy radio waves to treat liver tumors. Using CT and ultrasound guidance the doctor inserts a thin, needle-like probe into the liver tumor A high-frequency current is then passed through the tip of the probe, which heats the tumor with the goal to destroy the cancer cells. This may be done as an outpatient procedure or a short (1-2 day) hospital stay. PLA is the standard treatment for patients with liver cancer who cannot undergo liver surgery.
    Intervention: Procedure: Percutaneous Local Abalation
  • Active Comparator: Hypofractionated Image-Guided Radiation Therapy (HIGRT)
    HIGRT is an emerging treatment option for patients with HCC; it utilizes external radiation where multiple beams enter the body from multiple angles to treat the liver cancer over typically 5-10 treatments while minimizing radiation to normal tissues. You will receive between 5-10 fractions (treatments) of radiation. Fraction size will be either 5 or 10 Gy (pronounced Gray, a standard unit of radiation measurement) depending on your tumor size and location or underlying liver function. The total dose of radiation is 50 Gy.
    Intervention: Radiation: Hypofractionated Image Guided Radaition Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: January 17, 2018)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2026
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient has signed informed consent
  • HCC diagnosed either by histology/pathology or Liver Imaging Reporting and Data System (LIRADs 5 per the ACR's LIRADs criteria) by CT or MRI
  • Patient is 18 years or older
  • ECOG Performance status of 0-2
  • Child Pugh score A5, A6, B7 or B8
  • Lesions less than or equal to 5cm in size
  • Less than or equal to 3 lesions in the liver to be treated on protocol
  • Lesion amenable to treatment with both PLA and HIGRT; for PLA treatment this requires the lesion be visible via ultrasound and/or non-contrast CT or feasible per treating physician

Exclusion Criteria:

  • Child Pugh score B9 or C10
  • Fluctuating ascites
  • Inability to complete baseline QOL forms
  • Concurrent administration of systemic therapy for HCC
  • Prior liver RT is an exclusion unless subject participation is approved by the PI
  • Positive serum pregnancy test
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03402607
Other Study ID Numbers  ICMJE Pro00089525
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE
  • Durham VA Medical Center
  • Hunter Holmes McGuire VA Medical Center
Investigators  ICMJE
Principal Investigator: Brian Czito, MD Duke University
PRS Account Duke University
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP