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Sorafenib Tosylate and Hydroxychloroquine Sulfate in Treating Patients with Advanced or Metastatic Liver Cancer

Trial Status: Active

This phase II trial studies how well sorafenib tosylate and hydroxychloroquine sulfate work in treating patients with liver cancer that has spread to other parts of the body (advanced or metastatic). Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hydroxychloroquine sulfate may increase the effectiveness of sorafenib tosylate. Giving sorafenib tosylate and hydroxychloroquine may work better in treating patients with liver cancer.

Inclusion Criteria

  • Cytologically or histologically confirmed advanced or metastatic HCC; if no histological diagnosis, patient must have imaging studies compatible with HCC
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Not a candidate for curative treatments (i.e., resection, transplantation)
  • Child-Pugh class A or B7-8 liver function
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Patients who received prior local therapy (e.g., transarterial chemoembolization [TACE]) are eligible
  • Documented virology status of hepatitis, as confirmed by screening anti-hepatitis B surface antigen (HBsAg), anti-hepatitis B virus core antibody (HBc), and/or anti-hepatitis C virus (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
  • Granulocyte count > 1500/mm^3 (within 21 days prior to cycle 1 day 1)
  • Platelet count > 75,000/mm^3 (within 21 days prior to cycle 1 day 1)
  • Hemoglobin > 8 g/dL (within 21 days prior to cycle 1 day 1)
  • Total bilirubin < 2.0 (within 21 days prior to cycle 1 day 1)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 5 x upper limit of normal (ULN) (within 21 days prior to cycle 1 day 1)
  • Serum creatinine < 1.5 x ULN (within 21 days prior to cycle 1 day 1)
  • Able to provide written informed consent
  • Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the investigational product
  • COHORT 1 (WITH SORFENIB): No previous systemic therapy with sorafenib or previous immunotherapy, TACE and local treatments are permitted
  • COHORT 2 (ON PROGRESSION OF SORAFEINIB): Patients who have received prior sorafenib therapy for at least 4 weeks and has confirmation of disease progression on computed tomography/magnetic resonance imaging (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 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
  • Major surgery or significant traumatic injury occurring within 21 days prior to treatment
  • Corrected QT (QTc) > 500 ms at baseline (on a single electrocardiogram [EKG]) or average of 3 determinations at 10-minute intervals
  • 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 nasojejunal (NJ), jejunostomy (J) or gastrostomy (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
  • 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


San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Status: ACTIVE
Contact: Sukeshi Patel Arora
Phone: 210-450-1015


I. To determine the clinical efficacy with time to tumor progression (TTP) of the combination of hydroxychloroquine sulfate (HCQ) and sorafenib tosylate (sorafenib) in sorafenib-naive advanced hepatocellular carcinoma (HCC) (cohort 1); and the addition of HCQ to sorafenib in patients who progress on sorafenib (cohort 2).


I. To determine the overall survival in advanced HCC patients receiving HCQ and sorafenib in both cohort 1 and 2.

II. To evaluate the tumor response rate in advanced HCC patients receiving HCQ and sorafenib.

III. To further define the safety in advanced HCC patients receiving HCQ and sorafenib.

IV. To identify biomarkers of autophagy modulation and immune markers that correlate with clinical efficacy in advanced HCC patients receiving HCQ and sorafenib.


Patients receive sorafenib tosylate orally (PO) twice daily (BID) and hydroxychloroquine sulfate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

Principal Investigator
Sukeshi Patel Arora

  • Primary ID CTMS 16-0076
  • Secondary IDs NCI-2017-00157, HSC20160515H
  • ID NCT03037437