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Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer

Primary Purpose

Hepatocellular Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sorafenib (SOR)
Hydroxychloroquine (HCQ)
Sponsored by
The University of Texas Health Science Center at San Antonio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Cancer focused on measuring Hepatocellular Cancer, Sorafenib, Hydroxychloroquine

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Cytologically or histologically confirmed advanced or metastatic HCC. If no histological diagnosis, patient must have imaging studies compatible with HCC.
  • Age 18 years and above
  • ECOG performance status of 0 or 1
  • Not a candidate for curative treatments (i.e., resection, transplantation)
  • Child-Pugh class A or B7 liver function
  • Measurable disease as defined by RECIST 1.1
  • Patients who received prior local therapy (e.g., TACE) are eligible.
  • Documented virology status of hepatitis, as confirmed by screening HBsAg, anti-HBc, and/or anti-HCV
  • Life expectancy> 3 months
  • For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two adequate methods of contraception. For men: agreement to use a barrier method of contraception during the treatment period
  • Hematologic, Biochemical, and Organ Function within 7 days prior to Cycle 1 Day 1: Granulocyte count > 1500/mm3, Platelet count > 75,000/ mm3, Hemoglobin > 8 g/dL; Total bilirubin < 2.0; Albumin > 2.8g/dl; AST (SGOT) and ALT (SGPT) < 5 x ULN; Serum creatinine< 1.5 x ULN
  • Cohort 1 (with sorafenib): No previous systemic therapy including sorafenib or chemotherapy treatment. Previous TACE and local treatments are permitted.
  • Cohort 2 (on progression of sorafenib): Patients who have received prior sorafenib therapy for at least 4 weeks and has confirmation of disease progression on CT/MRI. Prior surgery or local therapy within 4 weeks prior to Cycle 1 Day 1, with the exception of palliative radiation therapy to the bone

Exclusion Criteria:

  • Patients receiving prior therapy with HCQ.
  • Patients with uncontrolled brain metastases. Patients with brain metastases must be asymptomatic and off corticosteroids for at least one week.
  • Due to risk of disease exacerbation, patients with psoriasis are ineligible unless the disease is well controlled, and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations.
  • Patients with previously documented macular degeneration or or untreated diabetic retinopathy (stable retinopathy is allowed).
  • Patients may not be receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to HCQ.
  • Patients requiring the use of enzyme-inducing anti-epileptic medication (phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine) are not eligible for entry into the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • QTc > 500 milliseconds (ms) at baseline.
  • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease. Patients with NG-tube, J-tube, or G-tube will not be allowed to participate.
  • Pregnant women are excluded from this study because sorafenib has the potential for teratogenic or abortifacient effects. For this reason, women of childbearing potential and men must also agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.
  • Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib, breastfeeding should be discontinued.
  • Informed Consent - No study specific procedures will be performed without a written and signed informed consent document. Patients who do not demonstrate the ability to understand or the willingness to sign the written informed consent document will be excluded from study entry.

Sites / Locations

  • University of Texas Health Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

No prior systemic treatment

Progress on sorafenib

Arm Description

Sorafenib (SOR)-naïve patients receive SOR 400 mg by PO twice daily on Cycle1/Day1 (C1D1). In clinical practice, dose reduction of SOR is often required. Therefore, on C1D15, the clinician will dose-reduce sorafenib based on toxicity and hydroxychloroquine (HCQ) 400 mg PO daily will be started. C2D1 of each cohort, toxicity of HCQ will be assessed. Dose reductions due to adverse events (AEs) to each agent are allowed for SOR per standard of care and/or HCQ for grade 3+ AE.

As second-line treatment, we will add hydroxychloroquine (HCQ) to sorafenib (SOR) dose the patient was tolerating at the time of progression.

Outcomes

Primary Outcome Measures

Time to tumor progression evaluated via tumor imaging
Computerized axial tomography (CAT) Scan or Magnetic resonance imaging (MRI) will be done at Screening, then every other cycle and evaluated using RECIST version 1.1

Secondary Outcome Measures

Full Information

First Posted
January 19, 2017
Last Updated
June 28, 2023
Sponsor
The University of Texas Health Science Center at San Antonio
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1. Study Identification

Unique Protocol Identification Number
NCT03037437
Brief Title
Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer
Official Title
Modulation of Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 16, 2017 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center at San Antonio

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The PI is studying if sorafenib/hydroxychloroquine (HCQ) will have improved efficacy when compared to sorafenib alone and in patients progressing of sorafenib the addition of HCQ would lead to disease stability in patients with advanced hepatocellular cancer (HCC).
Detailed Description
Phase 2 study with two cohorts: Cohort 1: As second-line treatment, we will add HCQ to SOR dose the patient was tolerating at the time of progression. Cohort 2: SOR-naïve patients receive SOR 400 mg by PO twice daily on Cycle1 Day1 (C1D1). On Cycle 1 Day 15, HCQ 400 mg PO daily will be started. In clinical practice, dose reduction of SOR may be required. On C1D15 SOR maybe kept as starting dose or reduced for toxicity. On Cycle 2 Day 1 of toxicity of HCQ and SOR will be assessed. Each cycle is 28 days. Blood samples will be collected at Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 to assess for biomarkers. Disease evaluation every 2 cycles. Dose reductions due to adverse events are allowed for both sorafenib per standard of care and/or HCQ for grade 3 or more adverse event was related to study medication. Dose reductions are also permitted based on investigator clinical decision.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Cancer
Keywords
Hepatocellular Cancer, Sorafenib, Hydroxychloroquine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
No prior systemic treatment
Arm Type
Experimental
Arm Description
Sorafenib (SOR)-naïve patients receive SOR 400 mg by PO twice daily on Cycle1/Day1 (C1D1). In clinical practice, dose reduction of SOR is often required. Therefore, on C1D15, the clinician will dose-reduce sorafenib based on toxicity and hydroxychloroquine (HCQ) 400 mg PO daily will be started. C2D1 of each cohort, toxicity of HCQ will be assessed. Dose reductions due to adverse events (AEs) to each agent are allowed for SOR per standard of care and/or HCQ for grade 3+ AE.
Arm Title
Progress on sorafenib
Arm Type
Experimental
Arm Description
As second-line treatment, we will add hydroxychloroquine (HCQ) to sorafenib (SOR) dose the patient was tolerating at the time of progression.
Intervention Type
Drug
Intervention Name(s)
Sorafenib (SOR)
Other Intervention Name(s)
Nexavar
Intervention Description
Patients will receive SOR 400 mg by PO twice daily on Cycle1/Day1 (C1D1).
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine (HCQ)
Other Intervention Name(s)
Plaquenil
Intervention Description
400mg by mouth daily
Primary Outcome Measure Information:
Title
Time to tumor progression evaluated via tumor imaging
Description
Computerized axial tomography (CAT) Scan or Magnetic resonance imaging (MRI) will be done at Screening, then every other cycle and evaluated using RECIST version 1.1
Time Frame
Through study completion, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cytologically or histologically confirmed advanced or metastatic HCC. If no histological diagnosis, patient must have imaging studies compatible with HCC. Age 18 years and above ECOG performance status of 0 or 1 Not a candidate for curative treatments (i.e., resection, transplantation) Child-Pugh class A or B7 liver function Measurable disease as defined by RECIST 1.1 Patients who received prior local therapy (e.g., TACE) are eligible. Documented virology status of hepatitis, as confirmed by screening HBsAg, anti-HBc, and/or anti-HCV Life expectancy> 3 months For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two adequate methods of contraception. For men: agreement to use a barrier method of contraception during the treatment period Hematologic, Biochemical, and Organ Function within 7 days prior to Cycle 1 Day 1: Granulocyte count > 1500/mm3, Platelet count > 75,000/ mm3, Hemoglobin > 8 g/dL; Total bilirubin < 2.0; Albumin > 2.8g/dl; AST (SGOT) and ALT (SGPT) < 5 x ULN; Serum creatinine< 1.5 x ULN Cohort 1 (with sorafenib): No previous systemic therapy including sorafenib or chemotherapy treatment. Previous TACE and local treatments are permitted. Cohort 2 (on progression of sorafenib): Patients who have received prior sorafenib therapy for at least 4 weeks and has confirmation of disease progression on CT/MRI. Prior surgery or local therapy within 4 weeks prior to Cycle 1 Day 1, with the exception of palliative radiation therapy to the bone Exclusion Criteria: Patients receiving prior therapy with HCQ. Patients with uncontrolled brain metastases. Patients with brain metastases must be asymptomatic and off corticosteroids for at least one week. Due to risk of disease exacerbation, patients with psoriasis are ineligible unless the disease is well controlled, and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations. Patients with previously documented macular degeneration or or untreated diabetic retinopathy (stable retinopathy is allowed). Patients may not be receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical or biologic composition to HCQ. Patients requiring the use of enzyme-inducing anti-epileptic medication (phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine) are not eligible for entry into the study. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements QTc > 500 milliseconds (ms) at baseline. Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease. Patients with NG-tube, J-tube, or G-tube will not be allowed to participate. Pregnant women are excluded from this study because sorafenib has the potential for teratogenic or abortifacient effects. For this reason, women of childbearing potential and men must also agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib, breastfeeding should be discontinued. Informed Consent - No study specific procedures will be performed without a written and signed informed consent document. Patients who do not demonstrate the ability to understand or the willingness to sign the written informed consent document will be excluded from study entry.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Epp Goodwin
Phone
210-450-5798
Email
ctrcreferral@uthscsa.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sukeshi Patel Arora, MD
Phone
210-450-1015
Email
aroras@uthscsa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sukeshi Patel Arora, MD
Organizational Affiliation
Cancer Therapy & Research Center University of Texas Health Science Center San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Health Cancer Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Epp Goodwin
Phone
210-450-5798
Email
goodwine@uthscsa.edu

12. IPD Sharing Statement

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Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer

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