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 |
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Recruitment Status :
Active, not recruiting
First Posted : March 25, 2019
Last Update Posted : August 20, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatitis B Virus Positive Malignant Solid Neoplasm | Other: Best Practice Other: Laboratory Biomarker Analysis Drug: Tenofovir Alafenamide | Phase 3 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 444 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Prevention |
| Official Title: | 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 |
| Actual Study Start Date : | February 21, 2019 |
| Estimated Primary Completion Date : | February 21, 2025 |
| Estimated Study Completion Date : | February 21, 2025 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Other: Laboratory Biomarker Analysis
Correlative studies Drug: Tenofovir Alafenamide Given PO
Other Names:
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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.
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Other: Laboratory Biomarker Analysis
Correlative studies Drug: Tenofovir Alafenamide Given PO
Other Names:
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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.
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Other: Best Practice
Receive best practice
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Tenofovir Alafenamide Given PO
Other Names:
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- Time until adverse liver outcome [ Time Frame: Up to 24 months ]Calculated as from date of randomization to date of first adverse liver outcome. 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.
- Time until hepatitis B Virus (HBV) reactivation [ Time Frame: Up to 24 months ]
Calculated as from date of randomization to date of first HBV reactivation. HBV reactivation defined as one of the following:
- ≥ 2 log (100-fold) increase in HBV DNA compared to baseline in patients with detectable HBV DNA at baseline, or
- HBV DNA ≥ 3 log (1,000) IU/mL in a patient with previously undetectable HBV DNA, or
- HBV DNA ≥ 4 log (10,000) IU/mL if baseline HBV DNA not available, or
- HBsAg seroreversion (HBsAg- to HBsAg+) in a patient previously HBsAg-
- Time until HBV Reactivation or Adverse Liver Outcome [ Time Frame: Up to 24 months ]Calculated as from date of randomization to date of first adverse liver outcome or HBV activation, whichever occurs first.
- Time until Hepatits Flare [ Time Frame: Up to 24 months ]Calculated as from date of randomization to date of first hepatitis flare. Hepatitis flare defined as alanine aminotransferase (ALT) > 3 x baseline and > 100 U/L.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03887702
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| Principal Investigator: | Jessica P Hwang | Southwest Oncology Group |
| Responsible Party: | Southwest Oncology Group |
| ClinicalTrials.gov Identifier: | NCT03887702 |
| Other Study ID Numbers: |
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 ) |
| First Posted: | March 25, 2019 Key Record Dates |
| Last Update Posted: | August 20, 2020 |
| Last Verified: | August 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Hepatitis A Hepatitis B Hepatitis Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections |
DNA Virus Infections Tenofovir Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents |