Prophylactic Antiviral Therapy in Patients With Current or Past Hepatitis B Virus Infection Receiving Anti-Cancer Therapy for Solid Tumors
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| ClinicalTrials.gov Identifier: NCT03887702 |
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Recruitment Status :
Recruiting
First Posted : March 25, 2019
Last Update Posted : August 12, 2021
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Sponsor:
Southwest Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group
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Brief Summary:
This phase III trial studies the effect of tenofovir alafenamide in preventing liver complications in patients 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 patients receiving anti-cancer therapy for solid tumors.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatitis B Infection Malignant Solid Neoplasm | Other: Best Practice Drug: Entecavir Drug: Tenofovir Alafenamide Drug: Tenofovir Disoproxil Fumarate | Phase 3 |
Show detailed description
| 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 1, 2026 |
| Estimated Study Completion Date : | February 2027 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Entecavir
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group A (TAF, TDF, entecavir)
Patients receive TAF PO QD or TDF PO QD or entecavir PO QD immediately or within 42 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.
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Drug: Entecavir
Given PO
Other Names:
Drug: Tenofovir Alafenamide Given PO
Other Names:
Drug: Tenofovir Disoproxil Fumarate Given PO
Other Names:
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Experimental: Group B (TAF, TDF, entecavir)
Patients receive TAF PO QD or TDF PO QD or entecavir 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.
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Drug: Entecavir
Given PO
Other Names:
Drug: Tenofovir Alafenamide Given PO
Other Names:
Drug: Tenofovir Disoproxil Fumarate Given PO
Other Names:
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Experimental: Group C (TAF, TDF, entecavir, usual care)
Patients receive TAF PO QD or TDF PO QD or entecavir 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.
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Other: Best Practice
Receive best practice
Other Names:
Drug: Entecavir Given PO
Other Names:
Drug: Tenofovir Alafenamide Given PO
Other Names:
Drug: Tenofovir Disoproxil Fumarate Given PO
Other Names:
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Primary Outcome Measures :
- Time until adverse liver outcome, assessed by incidence of adverse liver outcome [ Time Frame: From the start of study treatment up to 24 months ]Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0. 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.
Secondary Outcome Measures :
- 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 [ Time Frame: Up to 24 months ]Defined as alanine aminotransferase (ALT) > 3 x baseline and > 100 U/L.
- Initiation of upon indication tenofovir alafenamide (TAF) therapy [ Time Frame: Up to 24 months ]
- Cancer therapy interruption [ Time Frame: Up to 24 months ]Defined as dose reduction, treatment delay, or termination of anti-cancer therapy due to hepatic-related reasons other than disease progression in the liver.
- Death due to any cause [ Time Frame: From date of randomization up to 24 months ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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, or non-invasive (in situ) malignancies of the cervix, breast, or skin
- 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 =< 42 days after the initiation of first cycle of anti-cancer therapy
- 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 results for the following HBV tests done within 28 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 =< 42 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
- International normalized ratio (INR) must be completed =< 28 days prior to registration; results must < 1.2 x institutional limits of normal
- Alanine aminotransferase (ALT) must be obtained =< 28 days prior to registration; ALT must be =< 1.5 x institutional ULN
- Total bilirubin must be obtained =< 28 days prior to registration; total bilirubin must be =< 1.5 x institutional ULN
- Creatinine results must be obtained =< 28 days prior to registration; creatinine must be =< 1.5 x institutional ULN
- Patients must not have known current active hepatitis C infection (HCV); active HCV is defined by a detectable HCV ribonucleic acid (RNA) level; Note: HCV testing is not required for eligibility
- 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
- Patients must have Zubrod performance status of 0-2
- 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 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)
- 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
Information from the National Library of Medicine
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
Locations
Show 193 study locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
| 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 12, 2021 |
| Last Verified: | August 2021 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Infections Communicable Diseases Hepatitis A Hepatitis B Hepatitis Disease Attributes Pathologic Processes Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections |
Blood-Borne Infections Hepadnaviridae Infections DNA Virus Infections Tenofovir Entecavir Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents |