Randomized Trial of Prophylactic Antiviral Therapy in Patients with Current or Past Hepatitis B Virus (HBV) Infection Receiving Cytotoxic Therapy for Solid Tumors

- 5.1 Disease Related Criteria

a. Patients must be diagnosed with Stage I-III solid tumor malignancy. Patients with only carcinoma in situ or with Stage IV disease are excluded.

b. Patients must not have been diagnosed with a malignancy other than the current malignancy within the past five years, with the exception of basal cell or squamous cell skin cancer, or non-invasive (in situ) malignancies of the cervix, breast, or skin.

c. Patients must not have lymphoma, leukemia, or myeloma.

d. Patients must not have primary liver cancer, known cirrhosis, or evidence of any malignancy that involves the liver.

5.2 Prior/Concurrent Therapy Criteria

a. Patients must be planning to receive systemic anti-cancer therapy (either single agent or some combination of systemic cytotoxic therapy, systemic immunotherapy or systemic targeted therapy) for this solid tumor.

b. Patients must not have been previously treated with the same anti-cancer therapy regimen that is now anticipated. The anti-cancer therapy does not have to be first-line therapy. Prior and/or concurrent radiotherapy is allowed.

c. Patients must be registered <= 28 days prior to the planned start date of anti-cancer therapy. If the patient has started systemic anti-cancer therapy, patient must be registered <= 42 days after the initiation of first cycle of anti-cancer therapy.

d. Patients who have received prior anti-cancer therapy must have discontinued all previous therapies (excluding planned anti-cancer therapy to occur in conjunction with this study) >= 1 day prior to registration to this study.

e. Patients must not have had any cancer therapy regimen that includes anti-CD20.

f. Patients must not be receiving antiviral medications active against HBV, including: adefovir, entecavir, lamivudine, telbivudine, tenofovir disoproxil fumarate, tenofovir alafenamide (TAF), or any other FDA approved agents for the treatment of Hepatitis B. Patients who have previously received antiviral medication must not have required any antiviral medication active against HBV >= 90 days prior to registration to this study.

g. Patients must not have had hematopoietic stem cell transplantation therapy.

h. Patients receiving any of the following medications must discontinue them (under the supervision of their treating physician) prior to registration, and must not be planning to take them during protocol therapy: acyclovir, aminoglycosides, coumadin/warfarin, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, valacyclovir, high-dose NSAIDs (“high-dose” based on package insert), and St. John’s Wort.

5.3 Clinical/Laboratory Criteria

a. Patients must have results for the following HBV tests done within 28 days prior to registration: HBsAg AND anti-HBc (total Ig or IgG, but not IgM only) AND anti-HBs. For the anti-HBs test, quantitative or qualitative (including “indeterminate”) results are allowable. Refer to Appendix 18.2 for viral status information.

b. Patients must have tested positive for HBsAg or anti-HBc (total Ig, IgG, but not IgM) and must have baseline HBV DNA completed <= 42 days prior to registration. See Appendix 18.2 for viral status information.

c. Complete blood count (CBC) must be completed <= 28 days prior to registration. Results do not need to be in the institutional limits of normal.

d. International Normalized Ratio (INR) must be completed <= 28 days prior to registration. Results must <1.2x institutional limits of normal.

e. ALT, total bilirubin and creatinine results must be obtained <= 28 days prior to registration. ALT, total bilirubin and calculated creatinine clearance must be < 1.5x institutional ULN.

Calculated creatinine clearance = (140 - age) x wt (kg) x 0.85 (if female)
72 x creatinine (mg/dl)

f. Patients must not have known current active hepatitis C infection (HCV). Active HCV is defined by a detectable HCV RNA level. Note: HCV testing is not required for eligibility.

g. Patients must not have a history of human immunodeficiency (HIV) infection. Patients with unknown HIV status must have HIV testing completed <= 365 days prior to registration.

h. Patients must have Zubrod performance status of 0-2.

i. Patients must be at least 18 years old.

j. Patients must not be pregnant or nursing, as the safety of the study drug in pregnant and nursing women has not been established. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.

5.4 Specimen Submission Criteria

a. Patients must have specimens collected for submission as outlined in Section 15.1.

b. Patients must be offered the opportunity to participate in optional translational medicine studies as outlined in Section 15.2.

5.5 Regulatory Criteria

a. Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator).

b. Patients may have concurrent participation in other clinical trials that entail cytotoxic, immunotherapy, targeted therapy; surgical treatment; radiotherapy treatment; or any combination thereof.

c. Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

d. As a part of the OPEN registration process (see Section 13.3 for OPEN access instructions) the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.