Protocol for SARS-CoV-2 post-vaccine surveillance study in Australian adults and children with cancer: an observational study of safety and serological and immunological response to SARS-CoV-2 vaccination (SerOzNET)

Abstract

Background Cancer is associated with excess morbidity and mortality from coronavirus disease 2019 (COVID-19) following infection by the novel pandemic coronavirus SARS-CoV-2. Vaccinations against SARS-CoV-2 have been rapidly developed and proved highly effective in reducing the incidence of severe COVID-19 in clinical trials of healthy populations. However, patients with cancer were excluded from pivotal clinical trials. Early data suggest that vaccine response is less robust in patients with immunosuppressive conditions or treatments, while toxicity and acceptability of COVID-19 vaccines in the cancer population is unknown. Unanswered questions remain about the impact of various cancer characteristics (such as treatment modality and degree of immunosuppression) on serological response to and safety of COVID-19 vaccinations. Furthermore, as the virus and disease manifestations evolve, ongoing data is required to address the impact of new variants. Methods SerOzNET is a prospective observational study of adults and children with cancer undergoing routine SARS-CoV-2 vaccination in Australia. Peripheral blood will be collected and processed at five timepoints (one pre-vaccination and four post-vaccination) for analysis of serologic responses to vaccine and exploration of T-cell immune correlates. Cohorts include: solid organ cancer (SOC) or haematological malignancy (HM) patients currently receiving (1) chemotherapy, (2) immune checkpoint inhibitors (3) hormonal or targeted therapy; (4) patients who completed chemotherapy within 6–12 months of vaccination; (5) HM patients with conditions associated with hypogammaglobulinaemia or immunocompromise; (6) SOC or HM patients with allergy to PEG or polysorbate 80. Data from healthy controls already enrolled on several parallel studies with comparable time points will be used for comparison. For children, patients with current or prior cancer who have not received recent systemic therapy will act as controls. Standardised scales for quality-of-life assessment, patient-reported toxicity and vaccine hesitancy will be obtained. Discussion The SerOzNET study was commenced in June 2021 to prospectively study immune correlates of vaccination in specific cancer cohorts. The high proportion of the Australian population naïve to COVID-19 infection and vaccination at study commencement has allowed a unique window of opportunity to study vaccine-related immunity. Quality of life and patient-reported adverse events have not yet been reported in detail post-vaccination for cancer patients. Trial registration This trial is registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001004853. Submitted for registration 25 June 2021. Registered 30 July 2021 (Retrospectively registered). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382281&isReview=true

Evaluation of Safety and Side Effects COVID-19 Vaccine in Cancer Patients Being Treated

“…Covid-19 vaccines can help decrease problems in these patients, and this group are therefore prioritized in vaccination (Hwang et al, 2021); nevertheless, the issues requiring clarification in cancer patients receiving Covid-19 vaccines include the effects and potentially-significant side-effects of the vaccine in patients with immunodeficiency (Waleed et al, 2020), the risk of allergy to adjuvant substances in certain vaccines, the potential of these vaccines for protecting against severe Covid-19, and the prognosis and response to treatment considering interactions of the vaccine with the cancer and medications used. Treatments such as chemotherapy, immunotherapy and radiotherapy can counteract the effect of the vaccine (Noguchi et al, 2014;Body et al, 2022,). Although cytotoxic chemotherapeutics affect and suppress the proliferation and synthesis of (DNA) and the cell cycle, this suppression is incomplete and leads to the immune response to vaccination (Monin et al, 2021).…”

SARS-CoV-2 post-vaccine surveillance studies in Australian children and adults with cancer: SerOzNET Statistical Analysis Plan

“…The sample size of 100 per cohort will have over 80% power(of 0.80) to detect a decrease of 10% seroconversion rate in any cancer cohort (compared with assumed non-cancer population incidence of 95%) with 95% confidence (a of 0.05). (1)…”

SARS-CoV-2 post-vaccine surveillance studies in Australian children and adults with cancer: SerOzNET Quality of Life, Toxicity and Vaccine Beliefs Substudy Statistical Analysis Plan

“…A secondary aim of the study was to “document patient response to vaccination using qualitative measures, including patient-reported outcomes, vaccine hesitancy survey and post-hoc toxicity recording” (Body, et al, 2022). This statistical analysis plan describes the analysis of the data collected to address this aim.…”

“…The primary outcome of the main SerOzNET study is the seroconversion rate. According to the main study's sample size calculation (Body, et al, 2022), within a subgroup defined by cancer type, 100 individuals would provide 80% power to detect a decrease of 10% seroconversion rate compared to an assumed rate of 95% in a non-cancer population. This suggests a total sample size of 600 patients.…”

“…SerOzNET is a prospective cohort study of adults and children with cancer undergoing routine SARS-CoV-2 vaccination in Australia. Peripheral blood was collected and processed at multiple points (one pre-vaccination and five or more post-vaccination) to address the primary aim of the study to assess the serological and immunological responses to vaccination.A secondary aim of the study was to “document patient response to vaccination using qualitative measures, including patient-reported outcomes, vaccine hesitancy survey and post-hoc toxicity recording” (body, et al,2022). This statistical analysis plan describes the analysis of the data collected to address this aim.…”