Optimization for Regorafenib in HCC

NCT04476329 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 21305
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 9

Brief Summary

This is a randomized, two arm, phase II study of 1st Cycle dose optimization for regorafenib treatment compared to standard dose of regorafenib treatment in HCC patients for whom the physician is intending to treat with regorafenib and who failed any 1st line systemic treatment.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Liver Cancer; HCC; Regorafenib; Sorafenib; Stivarga

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  The primary objective is to evaluate whether, or not, an 80 mg/day starting dose of regorafenib that escalates weekly by 40 mg until 160 mg/day is non-inferior compared to the FDA approved labeling 160 mg starting dose of regorafenib in terms of Overall Survival in HCC subjects.

  24 months

Secondary Outcomes (6)

• Regorafenib treatment cycles

  24 months

• Tumor Progression

  24 months

• Dosing Patterns

  24 months

• EORTC QOL-C30 Quality of Life Measurements

  24 months

• Optional CD14-16 cell sub-study

  36 months

Study Arms (2)

A

ACTIVE COMPARATOR

Arm A: Regorafenib Cycle 1: * 80 mg daily Week 1 * 120 mg daily Week 2 * 160 mg daily week 3 then 1 week off followed by Cycle 2+ (160 mg for 21 days/1 week off) Subsequent Treatment Cycles * 160 mg daily for 21 days, then 1 week off.

Drug: Regorafenib 40 MG

B

ACTIVE COMPARATOR

Arm B: Regorafenib Cycle 1: * 160 mg daily for 21 days/then 1 week off Subsequent Treatment Cycles * 160 mg daily for 21 days, then 1 week off

Drug: Regorafenib 40 MG

Interventions

Regorafenib 40 MG DRUG

Regorafenib (BAY 73-4506) is an oral small molecule tyrosine kinase inhibitor (TKI) that potently blocks multiple protein kinases, including kinases involved in tumor angiogenesis (vascular endothelial growth factor receptor \[VEGFR\] 1, 2, 3, Tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 \[TIE2\]), stem cell growth factor receptor (KIT, rearranged during transfection \[RET\], p38-alpha, a member of the mitogen activated protein kinase \[MAPK\] family, proto-oncogene c-RAF \[c-RAF\], proto-oncogene BRAF \[BRAF\], BRAFV600E), metastasis (VEGFR3, platelet-derived growth factor receptor \[PDGFR\], fibroblast growth factor receptor1 \[FGFR1\]) and tumor immunity (colony stimulating factor 1 receptor \[CSF1R\]).

Also known as: Stivarga

A; B

Eligibility Criteria

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

You may qualify if:

• Patients age ≥ 18 years.
• Histological, cytological confirmation of hepatocellular carcinoma or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases (AASLD) criteria in patients with a confirmed diagnosis of cirrhosis.
• Locally advanced or metastatic and/or unresectable HCC that is not amenable or progressed after curative surgical and/or locoregional therapies.
• Patients who received one prior systemic treatment and for whom the treating physician has decided to treat with regorafenib.
• Life expectancy of ≥ 3 months.
• The following laboratory values obtained ≤ 7 days prior to randomization.
• Absolute neutrophil count (ANC) \> 1500/mm3
• Platelet count \> 60,000/mm3
• Hemoglobin \> 9.0 g/dL
• Albumin \> 2.7 gm/dL
• Total bilirubin \< 2 mg/dl (Mildly elevated total bilirubin (\< 6 mg/dL) is allowed if Gilbert's syndrome is documented)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5 x ULN
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance \> 50 mL/min (calculated using the Cockcroft-Gault formula)
• INR/PTT ≤ 1.5 x ULN
• Alkaline phosphatase limit ≤ 2.5 x ULN

You may not qualify if:

• Prior treatment with regorafenib.
• Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to randomization.
• Congestive heart failure \> New York Heart Association (NYHA) class 2.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) or myocardial infarction less than 6 months prior to randomization.
• Cardiac arrhythmias requiring anti-arrhythmic therapy. Note: beta blockers or digoxin are permitted.
• Uncontrolled hypertension. (Systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management).
• History of or current pheochromocytoma.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism ≤ 6 months prior to randomization.
• Ongoing infection \> grade 2 NCI-CTCAE version 5.0.
• Patients with seizure disorder requiring medication.
• Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of randomization and is clinically stable with respect to the tumor at the time of randomization.
• NOTE: Patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies).
• History of organ allograft (including corneal transplant), except prior liver transplant.
• Hepatic Encephalopathy requiring hospital admission within six (6) months prior to randomization.
• Ascites requiring paracentesis within four (4) weeks of randomization.

Sponsors & Collaborators

• SC Liver Research Consortium, LLC: lead
• Bayer: collaborator

Study Sites (9)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

VA Long Beach Health System

Long Beach, California, 90822, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Henry Ford Health Systems

Detroit, Michigan, 48202, United States

Location

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89014, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Catherine T Frenette, MD

  Scripps MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Madappa Kundranda, MD

  Banner MD Andersen Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This trial will not be masked, subjects will know which arm they are randomly assigned to.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm A will initiate Cycle 1 treatment at 80mg daily of regorafenib escalating up to but not exceeding 160mg daily at 40mg per week increments. Arm B will initiate Cycle 1 treatment at 160mg daily of regorafenib.

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 20, 2020
• Study Start: January 21, 2021
• Primary Completion: October 13, 2021
• Study Completion: December 10, 2021
• Last Updated: December 30, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)