Clinical trial NCT05025514: Retrospective Study of COVID-19 Vaccines in Patients Undergoing Immunotherapy for Cancer.
Official title: Pharmaco-epidemiological Study of COVID 19 Vaccines in Patients Undergoing Immunotherapy for Cancer. A Retrospective Open Cohort Study.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cancer
Immunotherapy
Keywords: Cancer
Covid-19
Vaccination
Immunotherapy
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
Collaborators: name: University Hospital, Montpellier
name: Institut du Cancer de Montpellier - Val d'Aurelle
name: Centre Hospitalier de Bagnols-sur-Cèze
name: Centre Hospitalier du Bassin de Thau
name: University Hospital, Toulouse
name: Centre Hospitalier de Cahors
name: Centre Hospitalier d'Auch
name: Centre Hospitalier Intercommunal de Castres
name: Centre Hospitalier d'Albi
name: Clinique Claude Bernard, Albi
name: Centre Hospitalier de Bigorre - Tarbes
name: Clinique La Croix du Sud Quint-Fonsegrives
name: Clinique Les Cèdres Cornebarrieu
name: Centre Hospitalier Ales
name: CENTRE HOSPITALIER COMMINGES PYRENEES
First posted: 2021-08-27
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of all patients with cancer requiring anti-PD, anti-PDL1 or antiCTLA4 immunotherapy for any tumour (solid, liquid) who have been vaccinated or eligible for vaccination against COVID19 (of any kind, except live, attenuated virus) and treated in the medical oncology departments of the Occitanie region.

Brief summary: The investigators wish to set up a pharmaco-epidemiological cohort within the Hospital Territorial Groups of the Cévennes-Gard Camargue, East-Hérault and Haute-Garonne and West Tarn on a specific population, patients undergoing immunotherapy for cancer, as currently there is no data available under "real life" conditions following anti-COVID vaccination19. The hypothesis is that patients undergoing immunotherapy will not develop more vaccine-related adverse events than those observed in the efficacy and safety validation studies of the BNT162b2 mRNA Covid-19, mRNA-1273 SARS CoV-2, Oxford/AstraZeneca and Ad26COV2.S, JMJ Vaccine or J \& J COVID-19 Vaccine.

Detailed description: The recent outbreak of Coronavirus 2019 (COVID-19) caused by a new zoonotic coronavirus SARS-Cov-2 poses a major public health threat, with at least 100,000,000 people infected worldwide by the end of January 2021 and over 2 million deaths. Given the scale of the pandemic, it has become imperative to quickly develop a vaccine and over 30 vaccine candidates have entered clinical evaluation. The first vaccine to receive marketing authorization in Europe and France was an mRNA vaccine, Comirnaty® (Bnt162b2; Pfizer/BioNtech). In a Phase III study of 43,448 participants, after a median follow-up of 2 months, the number of cases of COVID-19 was 8 in the vaccine arm vs. versus 162 in the placebo arm, respectively, with 1 versus 9 serious cases (Polack et al. 2020). Adverse events occurred in more than 50% of vaccinated participants and included local reactions as well as frequent systemic reactogenicity such as fatigue and headache. Fever occurred in about 15% of the participants who received the vaccine. The second vaccine to be licensed was also an mRNA vaccine: the Moderna COVID-19 mRNA (nucleoside modified) vaccine (mRNA-1273, Moderna). A Phase III trial involving 30,420 volunteers reported efficacy and safety comparable to the Pfizer/BioNtech vaccine. A severe form of COVID-19 occurred in 30 subjects, with one death; all 30 cases were in the placebo group. Moderate and transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group.

Serious adverse events were rare and the incidence was similar in both groups. Within the vaccination strategy implemented on a national level, the Comirnaty® vaccine (Pfizer/BioNtech) and the Moderna COVID-19 mRNA vaccine (nucleoside modified) may be used interchangeably, depending on logistical constraints.

For several weeks now, the Oxford-AstraZeneca chimpanzee adenovirus vector vaccine ChAdOx1 nCoV-19 (AZD1222) has been available in France and its efficacy and safety of use have been evaluated. Also the non-replicating viral vector (adenovirus) vaccine for CVD 19 from Janssen Laboratories (a subsidiary of Johnson \& Johnson; other names: Ad26COV2.S; JMJ Vaccine or J \& J COVID-19 Vaccine) was launched in France a few weeks ago. Its efficacy and safety have been validated in a phase III trial. A number of other candidate vaccines using various techniques such as mRNA, protein subunit, viral vector or inactivated vaccines are currently under investigation and will be available soon.

Cancer patients are particularly at risk of developing a severe form of COVID-19. Patients with solid tumors appear to be at a greater risk, particularly in the first year after diagnosis. Severity and mortality rates in the COVID-19 and Cancer Consortium (CCC19) registry and other cohorts range from 5% to 61% (a meta-analysis showed 26%), which is well above the general population. Although data on vaccination in cancer patients are limited, there is sufficient evidence to support anti-infective vaccination in general, even in cancer patients on immunosuppressive therapy. In its notice dated January 25th, 2021, the National Cancer Institute defined its recommendations for prioritizing cancer patients for vaccination against SARS-CoV-2. This report stresses that the data acquired from science is limited in quantity and quality concerning the emerging field of vaccination against SARS-CoV-2 and even more so in sub-populations including cancer patients. It reminds us that the challenge remains to vaccinate the entire population of patients who have or have had cancer, i.e. approximately 3.8 million people.

The level of efficacy can be expected to be generally reduced in certain cancer patient populations with intense immunosuppression, such as haematopoietic stem cell transplant recipients. However, based on extrapolation of data from other vaccines and the mechanism of action of COVID-19 (non-live) vaccines, it is conceivable that the efficacy and safety of COVID-19 vaccination could be estimated to be similar to that of non-cancer patients, although data from clinical trials are lacking. The efficacy and duration of immunity in cancer patients is still unknown and unexplored. It is therefore legitimate to propose surveillance through dedicated registries and clinical trials. Furthermore, close monitoring and follow-up of cancer patients is required after COVID-19 vaccination to assess potential adverse events and measure clinical outcomes, e.g. infection, severity and mortality from COVID-19, cancer complications etc... The investigators wish to set up a pharmaco-epidemiological cohort within the Hospital Territorial Groups of the Cévennes-Gard Camargue, East-Hérault and Haute-Garonne and West Tarn on a specific population, patients undergoing immunotherapy for cancer, as currently there is no data available under "real life" conditions following anti-COVID vaccination19. Our hypothesis is that patients undergoing immunotherapy will not develop more vaccine-related adverse events than those observed in the efficacy and safety validation studies of the BNT162b2 mRNA Covid-19, mRNA-1273 SARS CoV-2, Oxford/AstraZeneca and Ad26COV2.S, JMJ Vaccine or J \& J COVID-19 Vaccine.

Eligibility criteria: Inclusion Criteria:

* Patient having been vaccinated or eligible for inoculation with one of the available anti-COVID19 vaccines (except live attenuated virus) while they were or are undergoing immunotherapy with anti-PD1, anti-PDL1 or anti-CTLA4 immunotherapy whatever the tumor (solid, liquid) managed within the medical oncology services of the Occitanie region.
* Patients affiliated to or beneficiaries of a health insurance scheme.
* Patients who have received written and oral information about the study and who have no objection to participation.
* Adult patients (≥ 18 years).

Exclusion Criteria:

* Patients who have been vaccinated with a live attenuated vaccine.
* Patients with a contraindication to inclusion (including hypersensitivity to the active substance or to one of the excipients, COVID+ PCR test in the last 3 months).
* Minor patients, pregnant women, parturients, nursing mothers, persons in nursing mothers, persons in emergency situations, persons unable to persons unable to express their consent and persons under persons under court protection, subguardianship or subguardianship may not be included in this research.
* Patients in an exclusion period determined by another study.
* Patients for whom it is impossible to give clear information.
* Patients who have expressed an objection to participating in the study.

Primary outcomes:
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 24 hours after the vaccination
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 48 hours after the vaccination
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 8 days after the vaccination
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 24 hours after the following vaccination
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 48 hours after the following vaccination
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 8 days after the following vaccination
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 1 month after the following vaccination
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 3 months after the following vaccination
measure: Tolerance of immunotherapy following anti-COVID-19 vaccination
timeFrame: 6 months after the following vaccination
Secondary outcomes:
measure: A. Tolerance of immunotherapy after anti-COVID-19 vaccination
timeFrame: 24 hours after the vaccination
measure: A. Tolerance of immunotherapy after anti-COVID-19 vaccination
timeFrame: 48 hours after the vaccination
measure: A. Tolerance of immunotherapy after anti-COVID-19 vaccination
timeFrame: 8 days after the vaccination
measure: A. Tolerance of immunotherapy after anti-COVID-19 vaccination
timeFrame: 24 hours after the following vaccination
measure: A. Tolerance of immunotherapy after anti-COVID-19 vaccination
timeFrame: 48 hours after the following vaccination
measure: A. Tolerance of immunotherapy after anti-COVID-19 vaccination
timeFrame: 1 month after the following vaccination
measure: A. Tolerance of immunotherapy after anti-COVID-19 vaccination
timeFrame: 3 months after the following vaccination
measure: A. Tolerance of immunotherapy after anti-COVID-19 vaccination
timeFrame: 6 months after the following vaccination
measure: B.Response to vaccine: dosage of anti-Spike antibodies (ELISA)
timeFrame: Day 0
measure: B.Response to vaccine: dosage of anti-RBD antibodies (ELISA)
timeFrame: Day 0
measure: B. Response to vaccine: Lymphocyte count by Quantiferon
timeFrame: Day 0
measure: B. Response to vaccine: dosage of anti-Spike antibodies (ELISA)
timeFrame: 1 month after the injection
measure: B. Response to vaccine: dosage of anti-RBD antibodies (ELISA)
timeFrame: 1 month after the injection
measure: B. Response to vaccine: Lymphocyte count by Quantiferon
timeFrame: 1 month after the injection
measure: B. Response to vaccine: dosage of anti-spike antibodies (ELISA)
timeFrame: 1 month after the following injection
measure: B. Response to vaccine: dosage of anti-RBD antibodies (ELISA)
timeFrame: 1 month after the following injection
measure: B. Response to vaccine: Lymphocyte count by Quantiferon
timeFrame: 1 month after the following injection
measure: B. Response to vaccine: dosage of anti-spike antibodies (ELISA)
timeFrame: 3 months after the following injection
measure: B. Response to vaccine: dosage of anti-RBD antibodies (ELISA)
timeFrame: 3 months after the following injection
measure: B. Response to vaccine: Lymphocyte count by Quantiferon
timeFrame: 3 months after the following injection
measure: B. Response to vaccine: dosage of anti-spike antibodies (ELISA)
timeFrame: 6 months after the following injection
measure: B. Response to vaccine: dosage of anti-RBD antibodies (ELISA)
timeFrame: 6 months after the following injection
measure: B. Response to vaccine: Lymphocyte count by Quantiferon
timeFrame: 6 months after the following injection
measure: C. Efficacy of vaccination against the incidence of COVID-19
timeFrame: 1 month after vaccination
measure: C. Efficacy of vaccination against the incidence of COVID-19
timeFrame: 3 months after vaccination
measure: C. Efficacy of vaccination against the incidence of COVID-19
timeFrame: 6 months after vaccination
measure: D. Constitution of a biobank
timeFrame: Up to 6 months after vaccination
Other outcomes:
measure: Sex of patients
timeFrame: Day 0
measure: Age of patients
timeFrame: Day 0
measure: Weight of patients
timeFrame: Day 0
measure: Height of patients
timeFrame: Day 0
measure: Patients' WHO status
timeFrame: Day 0
measure: Type of cancer and its location
timeFrame: Day 0
measure: Treatment type
timeFrame: Day 0
measure: Therapeutic line
timeFrame: Day 0
measure: Other vaccinations
timeFrame: Day 0
measure: Lymphocyte count
timeFrame: Day 0
measure: COVID-19 serology test
timeFrame: Day 0
Locations:
city: Albi
country: France
facility: Clinique Claude Bernard
city: Albi
country: France
facility: Centre Hospitalier d'Albi
city: Alès
country: France
facility: Centre Hospitalier d'Alès
city: Auch
country: France
facility: CH d'Auch
city: Bagnols-sur-Cèze
country: France
facility: CH de Bagnols sur Cèze
city: Cahors
country: France
facility: CH de Cahors
city: Cornebarrieu
country: France
facility: Clinique des Cèdres - Capio
city: Montpellier
country: France
facility: Institut de Cancer de Montpellier
city: Quint-Fonsegrives
country: France
facility: Clinique La Croix du Sud
city: Saint-Gaudens
country: France
facility: Centre Hospitalier COMMINGES PYRENEES
city: Sete
country: France
facility: Centre Hospitalier du bassin de Thau
city: Tarbes Cedex 9
country: France
facility: CH de Bigorre
city: Toulouse
country: France
facility: Centre Hospitalier de Toulouse
Study officials:
affiliation: Centre Hospitalier Universitaire de Nīmes
name: Nadine HOUEDE, Professeur
role: PRINCIPAL_INVESTIGATOR
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