Clinical Trials /

Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer

NCT03037437

Description:

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).

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer
  • Official Title: Modulation of Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer

Clinical Trial IDs

  • ORG STUDY ID: CTMS 16-0076
  • SECONDARY ID: HSC20160515H
  • NCT ID: NCT03037437

Conditions

  • Hepatocellular Cancer

Interventions

DrugSynonymsArms
Sorafenib (SOR)NexavarNo prior systemic treatment
Hydroxychloroquine (HCQ)PlaquenilNo prior systemic treatment

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
No prior systemic treatmentExperimentalSorafenib (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.
  • Sorafenib (SOR)
  • Hydroxychloroquine (HCQ)
Progress on sorafenibExperimentalAs second-line treatment, we will add hydroxychloroquine (HCQ) to sorafenib (SOR) dose the patient was tolerating at the time of progression.
  • Sorafenib (SOR)
  • Hydroxychloroquine (HCQ)

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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to tumor progression evaluated via tumor imaging
Time Frame:Through study completion, an average of 1 year
Safety Issue:
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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The University of Texas Health Science Center at San Antonio

Trial Keywords

  • Hepatocellular Cancer
  • Sorafenib
  • Hydroxychloroquine

Last Updated

January 25, 2019