Prospective Study in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 Infection
- Conditions
- SARS-CoV-2 (COVID-19) InfectionAdvanced or Metastatic Hematological or Solid Tumor
- Interventions
- Registration Number
- NCT04333914
- Lead Sponsor
- Centre Leon Berard
- Brief Summary
A prospective, controlled, randomized, multicenter study whose goal is to compare the efficacy of an autophagy inhibitor (GNS561), an anti-NKG2A (monalizumab) and an anti-C5aR (avdoralimab) versus standard of care in patients with advanced or metastatic cancer who have Sars-CoV-2 infection not eligible to a resuscitation unit.
According to their severity level at the time of enrolment, eligible patients will be randomized into 2 different cohorts:
* COHORT 1 (mild symptoms or asymptomatic): GNS561 vs anti-NKG2A vs standard of care (randomization ratio 1:1:1).
* COHORT 2 (moderate/severe symptoms): anti-C5aR vs standard of care (randomization ratio 1:1).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description anti-C5aR (Avdoralimab) Standard of care - Autophagy inhibitor (GNS651) Autophagy inhibitor (GNS651) - Autophagy inhibitor (GNS651) Standard of care - Standard of care Standard of care - anti-NKG2A (Monalizumab) Standard of care - anti-C5aR (Avdoralimab) Avdoralimab - anti-NKG2A (Monalizumab) Monalizumab -
- Primary Outcome Measures
Name Time Method 28-day survival rate 28 days from randomization 28-day survival rate, defined by the proportion of patients still alive 28 days after randomization.
If vital status at 28 days post randomisation is not available due to early transfer in an external resuscitation unit, patients will be considered as failure at the date of the transfer.
Comparison of each experimental arm (GNS561 then monalizumab for cohort1 and avdoralimab for cohort2) to control arm will be performed using a Fisher exact test.
- Secondary Outcome Measures
Name Time Method Rate of throat swab negativation Day 7, Day 14, Day 28 Clinical status Day 7, Day 14, Day 28 The NEWS2 score (National Early Warning Score) allocates a score based on six physiological parameters (respiratory rate / oxygen saturation / systolic blood pressure / heart rate / consciousness / temperature).
It Determines the degree of illness of a patient and prompts critical care intervention.
The total possible score ranges from 0 to 21. The higher the score, the greater the clinical risk. A total score close to 0 corresponds to a low risk and a total score higher than 7 corresponds to a high risk.Length of stay in Intensive Care Unit 3 months (i.e. at the time of last patient last visit) The length of stay in Intensive Care Unit (from the date of admission in the Unit to the date of discharge).
Overall survival 3 months (i.e. at the time of last patient last visit) Overall survival will be defined by the time from date of randomization until date of death, regardless of the cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 3 months (i.e. at the time of last patient last visit) Treatment-Emergent Adverse Events, Serious Adverse Events, Suspected Unexpected Serious Adverse Reactions, New Safety Issues described using the NCI-CTC AE classification v5.
Number of participants with a discontinuation or temporary suspension of study drugs (for any reason).The rate of patients with SARS-CoV-2 IgG antibodies at D7, D14 and D28 Day 7, Day 14, Day 28 Mean change in the ranking of the NEWS2 score from baseline to D7, D14 and D28 Day 7, Day 14, Day 28 Mean change in clinical status from baseline will be assessed by using the NEWS2 score (National Early Warning Score).
The NEWS2 score (National Early Warning Score) allocates a score based on six physiological parameters (respiratory rate / oxygen saturation / systolic blood pressure / heart rate / consciousness / temperature).
It Determines the degree of illness of a patient and prompts critical care intervention.
The total possible score ranges from 0 to 21. The higher the score, the greater the clinical risk. A total score close to 0 corresponds to a low risk and a total score higher than 7 corresponds to a high risk.Biological parameters 3 months (i.e. at the the time of last patient last visit) Changes from baseline in pro-inflammatory cytokine (IL6)
Time to clinical improvement 28 days from randomization Time to clinical improvement defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale (WHO-ISARIC) or live discharge from the hospital, whichever comes first.
Mean change in the ranking on the ordinal scale from baseline to D7, D14 and D28 Day 7, Day 14, Day 28 Mean change in clinical status from baseline will be assessed by using a 7-point ordinal scale.
Duration of mechanical ventilation or high flow oxygen devices 3 months (i.e. at the time of last patient last visit) The duration of mechanical ventilation or high flow oxygen devices (from the date of intubation to the stop date of mechanical ventilation or high flow oxygen)
Quantitative SARS-CoV-2 virus in throat swab and blood samples Day 7, Day 14, Day 28 The rate of secondary infection by other documented pathogens (bacteria, fungi) Day 7, Day 14, Day 28 (if available) Duration of hospitalization 3 months (i.e. at the time of last patient last visit) The duration of hospitalization (from the date of hospitalization to the date of definitive discharge for live patients)
Cost-Effectiveness Analyses (CEA) 3 months (i.e. at the time of last patient last visit) Incremental Cost-Effectiveness Ratios (ICERs) expressed in cost per Life Year Gained.
Trial Locations
- Locations (12)
AP-HP Hôpital Bichat Claude Bernard
🇫🇷Paris, France
GH Diaconesses Croix Saint Simon
🇫🇷Paris, France
Institut Gustave Roussy
🇫🇷Villejuif, France
AP-HP Tenon
🇫🇷Paris, France
CHU Clermont Ferrand
🇫🇷Clermont Ferrand, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
AP-HP Hôpital Saint Antoine
🇫🇷Paris, France
Centre Oscar Lambret
🇫🇷Lille, France
AP-HP La Pitié Salpétrière
🇫🇷Paris, France
Hôpital Saint-Joseph
🇫🇷Paris, France
Centre Léon Bérard
🇫🇷Lyon, Rhône, France
Institut de cancérologie Strasbourg Europe (ICANS)
🇫🇷Strasbourg, France