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Samenvatting
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In ons onderzoeksproject ‘VOICE: Vaccination against cOvid In CancEr’ (onderdeel van het COVID-19 programma van NWO), onderzoeken we of behandelingen tegen kanker (chemotherapie, immunotherapie, of chemo-immunotherapie) invloed hebben op hoe patiënten met een solide tumor reageren op COVID-19 vaccinatie.

 

Het is een prospectieve longitudinale studie in patiënten met een solide tumor die een actieve behandeling tegen kanker ondergaan. Hiervoor worden meerdere cohorten, verspreid over verschillende centra in Nederland, bestudeerd. De immuunrespons in reactie op mRNA vaccinaties tegen COVID-19 wordt vergeleken tussen patiënten die chemo- en/of immunotherapie ondergaan enerzijds, en personen zonder kanker anderzijds. Naast het meten van de antilichaamrespons, worden ook de opgewekte immuunreactie in T-cellen, de bijwerkingen van de vaccinatie, en het voorkomen en de ernst van COVID-19 na vaccinatie bestudeerd.

 

We hebben reeds aangetoond dat de meeste patiënten met kanker, die worden behandeld met chemotherapie en/of immunotherapie tegen een solide tumor, een adequate antilichaamrespons ontwikkelen in reactie op twee vaccinaties met het mRNA-1273 COVID-19 vaccin. Het vaccin is ook veilig voor deze patiënten. Op dit moment worden de effecten van extra vaccinaties in de deelnemers onderzocht.

 

Resultaten
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De VOICE studie heeft aangetoond dat mRNA vaccins tegen COVID-19 veilig zijn voor patiënten met solide tumoren die actieve behandeling met chemo- en immunotherapie ondergaan. Recente resultaten wijzen erop dat vaccinaties van belang en veilig zijn voor deze groep patiënten, en hebben bijgedragen aan het beleid in Nederland omtrent een derde vaccinatie en tweede booster in deze patiëntengroep. De resultaten die tot nu toe gepubliceerd zijn, zijn vrij toegankelijk voor alle geïnteresseerden (een lijst van publicaties is te vinden via www.zonmw.nl/nl/over-zonmw/coronavirus/programmas/project-detail/covid-19-programma/voice-vaccination-against-covid-in-cancer/resultaten/).

Samenvatting van de aanvraag

Samenvatting
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RESEARCH QUESTION In patients with cancer, the disease and immunotherapy and chemotherapy may significantly impact the ability to develop an effective immune-response to COVID-19 vaccination and could even increase the risk of adverse events.

 

OBJECTIVE To assess immune-response and adverse events after vaccination with one vaccine against COVID-19 in patients with cancer treated with immunotherapy and/or chemotherapy.

 

STUDY DESIGN This is a prospective multicenter, multicohort study.

 

STUDY POPULATION 4 cohorts:

A. Individuals without cancer (partners of patients in cohort B, C & D)

Patients with cancer treated:

B. with immunotherapy

C. with chemotherapy

D. chemo-immunotherapy

 

Main inclusion criteria:

• > 17 years of age

• life expectancy > 12 months

• ability to provide informed consent

• last immunotherapy cycle <3 months of vaccination (cohort B & D)

• last chemotherapy cycle 4 weeks of vaccination (cohort C & D)

 

Main exclusion criteria:

• confirmed SARS-CoV-2 infection (current or previous)

• women who are pregnant or breastfeeding

• active hematologic malignancy

• immune-deficiency not related to cancer or cancer treatment

• systemic immune suppressive medication, including chronic steroid use >10 mg prednisone or equivalent

 

INTERVENTION Participants receive 2 vaccinations against COVID-19 according to the manufacturer’s instructions. Blood samples are collected before vaccination and at day 28 and 6 and 12 months after second vaccination. To evaluate vaccination related adverse events (AEs), patients will be asked to report local and systemic AEs for 7 days after each vaccination using a questionnaire. Similarly serious AEs (SAEs). Most patients receiving systemic cancer treatment experience multiple AEs, treatment or disease related. Vaccination related AEs are mainly expected within the first week after vaccination. Therefore, all immune related AEs = grade 3 are collected in cohorts B & D up to 28 days after last vaccination. Furthermore, AEs of special interest (AESIs) will be collected for the study duration in cohorts B-D.

Information on incidence of SARS-CoV-2 infection, outcome of COVID-19 during 12 months after vaccination is collected with questionnaires. For those who give separate consent, information on positive corona tests will also be collected from the RIVM.

 

ENDPOINTS The primary endpoint is the antibody-based immune-response on day 28 after the second vaccination. Participants will be classified as responders or non-responders. The definition of response will be based on a serological correlate of protection for COVID-19 based on SARS-CoV-2 spike (S)- protein-specific serum IgG antibody levels if established, and if not established, we will use seroconversion (= 4-fold increase of geometric mean concentration of anti-S protein IgG antibodies over baseline). This definition will be added before data analysis to ClinicalTrials.gov. The percentage of responders of each patient cohort will be compared with the percentage responders in the control group. Safety is a secondary endpoint is reported as percentage of solicited local and systemic AEs. Other secondary endpoints include longevity at 6 months and SARS-CoV-2 specific T cell response levels.

 

SAMPLE SIZE/DATA-ANALYSIS The primary endpoint is the antibody-based immune response day 28 after the second vaccination in patients receiving cancer treatment as compared to individuals without cancer. Participants are classified as responders or non-responders to vaccination against COVID-19. In patients treated with immunotherapy, we assume that the immune response rate is similar to that in individuals without cancer. In patients treated with chemotherapy or chemo-immunotherapy, we expect a lower immune response rate. As the percentage of responders is still unknown for vaccination against COVID-19, especially when a lower immune response rate is expected, a power calculation for different scenarios has been performed, thereby comparing cohorts B, C, and D separately with cohort A.

In summary, these power calculations indicate that for the cohort C vs A comparison and for the cohort D vs. A comparison we need 205 individuals without cancer, 205 patients treated with chemotherapy and 205 patients treated with chemo-immunotherapy. With these numbers we have enough power to assess noninferiority with an alpha of 0.05 and 80% power. In addition, we corrected for non-evaluable patients by increasing each cohort with 20%. This means that 246 participants will be recruited in cohorts A, C & D, and 135 participants in cohort B. In total, 873 participants (627 patients and 246 individuals without cancer) will be included.

 

EXPECTED RESULTS This study will generate information about immune response and side effects after vaccination against cancer in a vulnerable patient population. This information will support physicians and patients in deciding who should be vaccinated and identify patients who need other additional approaches to protect them against COVID-19.

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