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Tenofovir Alafenamide in Preventing Liver Complications in Participants With Current or Past Hepatitis B Virus Who Are Receiving Anti-Cancer Therapy for Solid Tumors

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ClinicalTrials.gov Identifier: NCT03887702
Recruitment Status : Recruiting
First Posted : March 25, 2019
Last Update Posted : September 9, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE March 21, 2019
First Posted Date  ICMJE March 25, 2019
Last Update Posted Date September 9, 2019
Actual Study Start Date  ICMJE February 21, 2019
Estimated Primary Completion Date February 21, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
Time until adverse liver outcome, assessed by incidence of adverse liver outcome graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0 [ Time Frame: From the start of study treatment up to 24 months ]
Adverse liver outcome defined as liver-related death or liver failure (ascites, hepatic encephalopathy or impaired hepatic synthetic function defined as total bilirubin >= 5 mg/dL or international normalized ration [INR] >= 2.0) not due to disease progression in the liver. The study will recruit patients with multiple different cancer types, but predominantly lung, breast, colon, prostate, gynecological, and head and neck cancers. Estimates of adverse liver outcomes at 1 year will be derived using cumulative incidence to account for the competing risk of death. The final analysis will rely on Cox regression, adjusting for the stratification factors.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Incidence of hepatitis B Virus (HBV) reactivation among patients with solid malignancies and chronic or past HBV infection during or after completion of anti-cancer therapy [ Time Frame: Up to 24 months ]
    Estimates of HBV reactivation at one year will be derived using cumulative incidence to account for competing risks. Under this scenario, a sample size of n=222 patients for each randomized study will allow the investigators to estimate the confidence interval to within +/- 6% (based on the upper bound of the 95% confidence interval using an exact binomial in patients with complete follow-up), if the assumed incidence is at least 20%. Thus, this sample size will allow the confidence interval to be estimated to within +/- 31.1% of the assumed incidence (the ?relative accuracy?, defined as: (95% confidence interval [CI] upper bound ? p)/p], where p is the assumed incidence).
  • HBV reactivation rate [ Time Frame: Up to 24 months ]
    The investigators will compare HBV reactivation rates by arm within each randomized trial. Based on a two-sample survival design accounting for the competing risk of death (~20% deaths at 1 year [hazard rate of 0.223]), and a one-sided alpha=0.05 test, then n=222 patients (111 per arm) will give 81% power to detect a hazard ratio for HBV reactivation for experimental to standard arms of 0.47, representing a 53% reduction in the hazard risk of HBV reactivation in the first year (from a hazard=0.223 down to hazard = 0.105), or an absolute reduction of 50% (from 20% down to 10%). Multivariable Cox regression will compare the effect of intervention assignment, adjusting for the stratification factors specified in the main clinical study.
  • Hepatitis flare defined as alanine aminotransferase (ALT) > 3 x baseline and > 100 U/L [ Time Frame: Up to 24 months ]
  • Initiation of upon indication tenofovir alafenamide (TAF) therapy [ Time Frame: Up to 24 months ]
  • Cancer therapy interruption defined as dose reduction, treatment delay, or termination of anti-cancer therapy due to hepatic-related reasons other than disease progression in the liver [ Time Frame: Up to 24 months ]
  • Death due to any cause [ Time Frame: From date of randomization up to 24 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tenofovir Alafenamide in Preventing Liver Complications in Participants With Current or Past Hepatitis B Virus Who Are Receiving Anti-Cancer Therapy for Solid Tumors
Official Title  ICMJE A Phase III Randomized Trial of Prophylactic Antiviral Therapy in Patients With Current or Past Hepatitis B Virus (HBV) Infection Receiving Anti-Cancer Therapy for Solid Tumors
Brief Summary This phase III trial studies how well tenofovir alafenamide works in preventing liver complications in participants with current or past hepatitis B virus (HBV) who are receiving anti-cancer therapy for solid tumors. People with chronic or past HBV who are undergoing therapy for cancer are at an increased risk for changes in the liver which could be minor or severe. Tenofovir alafenamide is a drug that acts against infections caused by HBV and may help reduce the chance that HBV gets worse or comes back in participants receiving anti-cancer therapy for solid tumors.
Detailed Description

PRIMARY OBJECTIVES:

I. To compare the effect of prophylactic tenofovir alafenamide (TAF) therapy versus upon indication TAF therapy on time-to-adverse liver outcomes of liver failure or liver-related death in patients with chronic HBV infection (hepatitis B surface antigen positive [HBsAg+] and antibody to hepatitis B core antigen positive [anti-HBc+]) receiving anti-cancer therapy for solid tumors.

II. To compare the effect of upon indication TAF therapy versus usual care on time-to-adverse liver outcomes of liver failure or liver-related death in patients with past HBV infection (hepatitis B surface antigen negative [HBsAg-] and anti-HBc+) receiving anti-cancer therapy for solid tumors.

SECONDARY OBJECTIVES:

I. Using time-to-event analysis, to compare the effect of TAF therapy versus upon indication TAF therapy on HBV reactivation, on the combined endpoint of adverse liver outcomes (liver failure or liver-related death) and HBV reactivation, and on HBV flare by arm in patients with chronic HBV infection receiving anti-cancer therapy for solid tumors.

II. Using time-to-event analysis, to compare the effect of upon indication TAF therapy versus usual care on HBV reactivation, on the combined endpoint of adverse liver outcomes (liver failure or liver-related death) and HBV reactivation, and on HBV flare by arm in patients with past HBV infection receiving anti-cancer therapy for solid tumors.

TRANSLATIONAL OBJECTIVES:

I. To compare baseline and changes in overall immune status and HBV-specific immune response in patients with solid tumors and chronic or past HBV infection receiving anti-cancer therapy, and to compare the differences in these immune responses by HBV reactivation status.

II. To identify demographic and clinical predictors and correlative immunologic biomarkers of HBV reactivation after receipt of anti-cancer therapy in patients with solid tumors and chronic or past HBV infection.

OUTLINE: Participants are randomized to 1 of 3 groups.

GROUP A (Cohorts 1a & 2a): Participants receive TAF orally (PO) once daily (QD) immediately or within 28 days after initial dose of chemotherapy. Treatment continues for up to 6 months after the last dose of chemotherapy or a maximum of 24 months in the absence of disease progression or unacceptable toxicity.

GROUP B (Cohorts 1b & 2b): Participants receive TAF PO QD after HBV reactivation during chemotherapy. Treatment continues for up to 6 months after the last dose of chemotherapy or a maximum of 24 months in the absence of disease progression or unacceptable toxicity.

GROUP C (Cohort 3): Participants receive TAF PO QD at the discretion of the physician during usual care. Treatment continues for up to 6 months after discontinuation of usual care or a maximum of 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up for up to 24 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Hepatitis B Virus Positive
  • Malignant Solid Neoplasm
Intervention  ICMJE
  • Other: Best Practice
    Receive best practice
    Other Names:
    • standard of care
    • standard therapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Tenofovir Alafenamide
    Given PO
    Other Names:
    • GS 7340
    • GS-7340
    • TFV Alafenamide
Study Arms  ICMJE
  • Experimental: Group A (tenofovir alafenamide)
    Participants receive TAF orally (PO) once daily (QD) immediately or within 28 days after initial dose of chemotherapy. Courses repeat for a maximum of 24 months in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Drug: Tenofovir Alafenamide
  • Experimental: Group B (tenofovir alafenamide)
    Participants receive TAF PO QD after HBV reactivation during chemotherapy. Courses repeat for a maximum of 24 months in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Drug: Tenofovir Alafenamide
  • Experimental: Group C (tenofovir alafenamide, usual care)
    Participants receive TAF PO QD at the discretion of the physician per usual care. Courses for a maximum of 24 months in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Best Practice
    • Other: Laboratory Biomarker Analysis
    • Drug: Tenofovir Alafenamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 21, 2019)
444
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 21, 2025
Estimated Primary Completion Date February 21, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must be diagnosed with stage I-III solid tumor malignancy; patients with only carcinoma in situ or with stage IV disease are excluded
  • 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, in situ cervical cancer, or in situ breast cancer
  • Patients must not have lymphoma, leukemia, or myeloma
  • Patients must not have primary liver cancer, known cirrhosis, or evidence of any malignancy that involves the liver
  • 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
  • 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
  • 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 =< 28 days after the initiation of first cycle of anti-cancer therapy or prior to the second cycle of the anti-cancer therapy, whichever occurs earlier
  • International normalized ratio (INR) must be completed =< 28 days prior to registration; results must be in the institutional limits of normal
  • 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
  • Patients must not have had any cancer therapy regimen that includes anti-CD20
  • Patients must not be receiving antiviral medications active against HBV, including: adefovir, entecavir, lamivudine, telbivudine, tenofovir disoproxil fumarate, tenofovir alafenamide (TAF), or any other Food and Drug Administration (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
  • Patients must not have had hematopoietic stem cell transplantation therapy
  • 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, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, valacyclovir, high-dose nonsteroidal anti-inflammatory drugs (NSAIDs), (?high-dose? based on package insert), and St. John?s wort
  • Patients must have complete results for the following HBV tests done =< 30 days prior to registration: HBsAg AND anti-HBc (total immunoglobulin [Ig] or IgG, but not IgM only) AND hepatitis B surface antibody (anti-HBs); for the anti-HBs test, quantitative or qualitative (including ?indeterminate?) results are allowable
  • Patients must have tested positive for HBsAg or anti-HBc (total Ig, IgG, but not IgM) and must have baseline HBV deoxyribonucleic acid (DNA) completed =< 90 days prior to registration
  • Complete blood count (CBC) must be completed =< 28 days prior to registration; results do not need to be in the institutional limits of normal
  • INR must be completed within 28 days prior to registration; results must be in the normal range
  • Alanine aminotransferase (ALT) must be obtained =< 28 days prior to registration; ALT must be within normal limits (> institutional lower limit of normal [ILLN] and < institutional upper limit of normal [IULN]) for the institution
  • Total bilirubin must be obtained =< 28 days prior to registration; total bilirubin must be within normal limits (> ILLN and < IULN) for the institution
  • Creatinine must be obtained =< 28 days prior to registration; creatinine must be within normal limits (> ILLN and < IULN) for the institution
  • Patients must not have known current active hepatitis C infection (HCV); active HCV is defined by a detectable HCV ribonucleic acid (RNA) level
  • Patients must not have a history of human immunodeficiency (HIV) infection; all patients must have HIV testing completed =< 365 days prior to registration
  • Patients must have Zubrod performance status of 0-2
  • Patients must be able to swallow tablets orally
  • 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
  • Patients must have specimens collected for submission as outlined
  • Patients must be offered the opportunity to participate in optional translational medicine studies as outlined
  • Patients may have concurrent participation in other clinical trials that entail cytotoxic, immunotherapy, targeted therapy; surgical treatment; radiotherapy treatment; or any combination thereof
  • 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
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03887702
Other Study ID Numbers  ICMJE S1614
NCI-2018-00592 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1614 ( Other Identifier: SWOG )
SWOG-S1614 ( Other Identifier: DCP )
S1614 ( Other Identifier: CTEP )
UG1CA189974 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Jessica P Hwang Southwest Oncology Group
PRS Account Southwest Oncology Group
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP