Clinical Trials /

Prospective Study in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 Infection

NCT04333914

Description:

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).

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Prospective Study in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 Infection
  • Official Title: Prospective, Controlled, Randomized, Multicenter Study to Compare the Efficacy of a Chloroquine Analog (GNS561), an Anti PD-1 (Nivolumab) and an Anti-interleukine-6 Receptor (Tocilizumab) vs Standard of Care in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 (COVID-19) Infection

Clinical Trial IDs

  • ORG STUDY ID: ET20-076 - IMMUNONCOVID-20
  • SECONDARY ID: 2020-001373-70
  • NCT ID: NCT04333914

Conditions

  • SARS-CoV-2 (COVID-19) Infection
  • Advanced or Metastatic Hematological or Solid Tumor

Interventions

DrugSynonymsArms
Chloroquine analog (GNS651)Chloroquine analog (GNS651)
NivolumabAnti-PD-1 (nivolumab)
TocilizumabAnti-IL-6 (tocilizumab)

Purpose

A prospective, controlled, randomized, multicenter study whose goal is to compare the efficacy of a chloroquine analog (GNS561), an anti PD-1 (nivolumab) and an anti-interleukine-6 receptor (tocilizumab) 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-PD1 vs standard of care (randomization ratio 1:1:1). - COHORT 2 (moderate/severe symptoms): GNS561 vs anti-IL6 vs standard of care (randomization ratio 1:1:1).

Trial Arms

NameTypeDescriptionInterventions
Chloroquine analog (GNS651)Experimental
  • Chloroquine analog (GNS651)
Anti-PD-1 (nivolumab)Experimental
  • Nivolumab
Anti-IL-6 (tocilizumab)Experimental
  • Tocilizumab
Standard of careOther

    Eligibility Criteria

            Inclusion Criteria:
    
            I1. Age 18 or older at the time of enrolment. I2. Histologically or cytologically confirmed
            diagnosis of advanced or metastatic hematological or solid tumor (hematological or solid
            tumor, any type and any localization).
    
            I3. Documented diagnosis of COVID-19 (diagnostic test performed in a certified laboratory)
            or symptoms of COVID-19 associated with radiological signs of pneumonia as described by Shi
            et al.; I4. Cohort 2: patients with pneumonia confirmed by chest imaging, and an oxygen
            saturation (Sao2) of 94% or less while they are breathing ambient air or a ratio of the
            partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) (Pao2:Fio2) at
            or below 300 mg Hg.
    
            I5. Patient not eligible for a transfer to Resuscitation Unit (either due to underlying
            medical condition - including cancer - or due to lack of available bed).
    
            I6. Life-expectancy longer than 3 months.
    
            I7. Adequate bone marrow and end-organ function defined by the following laboratory
            results:
    
              -  Bone marrow:
    
                   -  Hemoglobin ≥ 7.0 g/dL,
    
                   -  Absolute Neutrophils Count (ANC) ≥ 1.0 Gi/L,
    
                   -  Platelets ≥ 100 Gi/L;
    
              -  Hepatic function:
    
                   -  Total serum bilirubin ≤ 1.5 x ULN (except patients with Gilbert's syndrome who
                      must have total serum bilirubin ≤ 3.0 x ULN),
    
                   -  AST and ALT ≤ 5 ULN
    
              -  Renal function:
    
                   -  Serum creatinine ≤ 2.0 x ULN or Cr. Cl. ≥ 30ml/min/1.73m² (MDRD or CKD-EPI
                      formula); I8. Willingness and ability to comply with the study requirements; I9.
                      Signed and dated informed consent indicating that the patient has been informed
                      of all the aspects of the trial prior to enrolment (in case of emergency
                      situation, please refer to protocol section 13.1 PATIENT INFORMATION AND INFORMED
                      CONSENT); I10. Women of childbearing potential (Appendix 2) are required to have
                      a negative serum pregnancy test within 72 hours prior to study treatment start. A
                      positive urine test must be confirmed by a serum pregnancy test; I11. Women of
                      childbearing potential and male patients must agree to use adequate highly
                      effective contraception (Appendix 2) for the duration of study participation and
                      up to 6 months following completion of therapy; I12. Patient must be covered by a
                      medical insurance.
    
            Exclusion Criteria:
    
            E1. For cohort 1 only : Patient currently receiving therapy with an anti- PD-1, anti-
            PD-L1, or anti-CTLA4.
    
            E2. For cohort 2 only: Patient currently receiving therapy with an anti- IL-6 or
            anti-IL-6R.
    
            E3. Contraindication to treatment with nivolumab (cohort 1 only) or to tocilizumab (cohort
            2 only) as per respective SPC, including known hypersensitivity to one of these study drugs
            or severe hypersensitivity reaction to any monoclonal antibody.
    
            E4. Patient known to have intolerance or hypersensitivity to chloroquine or any quinoline
            derivates (e.g., quinine, chloroquine, mefloquine).
    
            E5. Patient has active autoimmune disease that has required systemic treatment in the past
            3 months before the date of randomisation or a documented history of clinically severe
            autoimmune disease, or a syndrome that requires systemic steroids at doses higher than 10
            mg/d prednisone equivalents or immunosuppressive agents.
    
            Note 1: Patients with vitiligo or resolved childhood asthma/atopy would be an exception to
            this rule. Patients that require intermittent use of bronchodilators or local steroid
            injections would not be excluded from the study. Patients with hypothyroidism stable on
            hormone replacement or Sjögren's syndrome will not be excluded from the study.
    
            Note 2: Patients may receive corticosteroids as required for the management of
            SARS-CoV-2-related symptoms.
    
            E6. Patient requires the use of one of the following forbidden treatment during the study
            treatment period:
    
              -  Major surgery.
    
              -  Live vaccines. Examples of live vaccines include, but are not limited to, the
                 following: measles, mumps, rubella, chicken pox, yellow fever and BCG. Seasonal
                 influenza vaccines for injection are generally killed virus vaccines and are allowed;
                 however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines,
                 and are not allowed.
    
            E7. Significant cardiovascular disease, such as New York Heart Association cardiac disease
            (Class II or greater), myocardial infarction within 3 months prior to the date of
            randomisation unstable arrhythmias or unstable angina, Known Left Ventricular Ejection
            Fraction (LVEF) < 50%.
    
            Note: Patients with known coronary artery disease, congestive heart failure not meeting the
            above criteria must be on a stable medical regimen that is optimized in the opinion of the
            treating physician and in consultation with a cardiologist if appropriate.
    
            E8. Patient has Active hepatitis B (chronic or acute; defined as having a positive
            hepatitis B surface antigen [HBsAg] test at screening), Active hepatitis C (Patients
            positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV
            RNA at screening) or Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibodies).
    
            E9. Prior allogeneic bone marrow transplantation or solid organ transplant in the past.
    
            E10. Has a history or current evidence of any condition, therapy, or laboratory abnormality
            that might confound the results of the trial, interfere with the subject's participation
            for the full duration of the trial, or is not in the best interest of the subject to
            participate, in the opinion of the treating Investigator.
    
            E11. Has known psychiatric or substance abuse disorders that would interfere with
            cooperation with the requirements of the trial.
    
            E12. Pregnant or breastfeeding patient, or expecting to conceive children within the
            projected duration of the trial, starting with the screening visit through 6 months after
            the last dose of study drugs.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:28-day survival rate
    Time Frame:28 days from randomization
    Safety Issue:
    Description:28-day survival rate, defined by the proportion of patients still alive 28 days after randomization. The 28-day survival rate will be described in each arm of each cohort.

    Secondary Outcome Measures

    Measure:Time to clinical improvement
    Time Frame:28 days from randomization
    Safety Issue:
    Description: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.
    Measure:Clinical status
    Time Frame:Day 7, Day 14, Day 28
    Safety Issue:
    Description:Clinical status will be assessed using a 7-point ordinal scale : Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.
    Measure:Mean change in clinical status from baseline to days
    Time Frame:Day 7, Day 14, Day 28
    Safety Issue:
    Description:Mean change in clinical status from baseline will be assessed using a 7-point ordinal scale.
    Measure:Overall survival
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description: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.
    Measure:Length of stay in Intensive Care Unit
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:The length of stay in Intensive Care Unit (from the date of admission in the Unit to the date of discharge).
    Measure:Duration of mechanical ventilation or high flow oxygen devices
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description: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)
    Measure:Duration of hospitalization
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:The duration of hospitalization (from the date of hospitalization to the date of definitive discharge for live patients)
    Measure:Rate of throat swab negativation
    Time Frame:Day 7, Day 14, Day 28
    Safety Issue:
    Description:
    Measure:Quantitative SARS-CoV-2 virus in throat swab and blood samples
    Time Frame:Day 7, Day 14, Day 28
    Safety Issue:
    Description:
    Measure:Rate of secondary infection by other documented pathogens
    Time Frame:Day 7, Day 14, Day 28 (if available)
    Safety Issue:
    Description:
    Measure:Biological parameters
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:Changes from baseline in neutrophils count (G/L)
    Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description: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).
    Measure:Cost-Effectiveness Analyses (CEA)
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:Incremental Cost-Effectiveness Ratios (ICERs) expressed in cost per Life Year Gained.
    Measure:Biological parameters
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:Changes from baseline in lymphocytes count (G/L)
    Measure:Biological parameters
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:Changes from baseline in platelets count (G/L)
    Measure:Biological parameters
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:Changes from baseline in hemoglobin count (g/dL)
    Measure:Biological parameters
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:Changes from baseline in CRP count (mg/L)
    Measure:Biological parameters
    Time Frame:3 months (i.e. at the the time of last patient last visit)
    Safety Issue:
    Description:Changes from baseline in pro-inflammatory cytokine (IL6)

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Centre Leon Berard

    Trial Keywords

    • Oncology
    • COVID-19
    • IL-6/IL-6 receptor pathway
    • Immunotherapy
    • GNS561

    Last Updated

    May 7, 2020