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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04333914
Recruitment Status : Suspended (Potential recrutment related to the epidemic context.)
First Posted : April 3, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Centre Leon Berard

Tracking Information
First Submitted Date  ICMJE April 1, 2020
First Posted Date  ICMJE April 3, 2020
Last Update Posted Date June 16, 2020
Actual Study Start Date  ICMJE April 15, 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2020)
28-day survival rate [ Time Frame: 28 days from randomization ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2020)
  • Time to clinical improvement [ Time Frame: 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.
  • Clinical status [ Time Frame: Day 7, Day 14, Day 28 ]
    Clinical status will be assessed using a 7-point ordinal scale :
    1. Not hospitalized, no limitations on activities
    2. Not hospitalized, limitation on activities;
    3. Hospitalized, not requiring supplemental oxygen;
    4. Hospitalized, requiring supplemental oxygen;
    5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    6. Hospitalized, on invasive mechanical ventilation or ECMO;
    7. Death.
  • Mean change in clinical status from baseline to days [ Time Frame: Day 7, Day 14, Day 28 ]
    Mean change in clinical status from baseline will be assessed using a 7-point ordinal scale.
  • Overall survival [ Time Frame: 3 months (i.e. at the 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.
  • Length of stay in Intensive Care Unit [ Time Frame: 3 months (i.e. at the 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).
  • Duration of mechanical ventilation or high flow oxygen devices [ Time Frame: 3 months (i.e. at the 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)
  • Duration of hospitalization [ Time Frame: 3 months (i.e. at the 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)
  • Rate of throat swab negativation [ Time Frame: Day 7, Day 14, Day 28 ]
  • Quantitative SARS-CoV-2 virus in throat swab and blood samples [ Time Frame: Day 7, Day 14, Day 28 ]
  • Rate of secondary infection by other documented pathogens [ Time Frame: Day 7, Day 14, Day 28 (if available) ]
  • Biological parameters [ Time Frame: 3 months (i.e. at the the time of last patient last visit) ]
    Changes from baseline in neutrophils count (G/L)
  • 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) ]
    • 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).
  • Cost-Effectiveness Analyses (CEA) [ Time Frame: 3 months (i.e. at the the time of last patient last visit) ]
    Incremental Cost-Effectiveness Ratios (ICERs) expressed in cost per Life Year Gained.
  • Biological parameters [ Time Frame: 3 months (i.e. at the the time of last patient last visit) ]
    Changes from baseline in lymphocytes count (G/L)
  • Biological parameters [ Time Frame: 3 months (i.e. at the the time of last patient last visit) ]
    Changes from baseline in platelets count (G/L)
  • Biological parameters [ Time Frame: 3 months (i.e. at the the time of last patient last visit) ]
    Changes from baseline in hemoglobin count (g/dL)
  • Biological parameters [ Time Frame: 3 months (i.e. at the the time of last patient last visit) ]
    Changes from baseline in CRP count (mg/L)
  • Biological parameters [ Time Frame: 3 months (i.e. at the the time of last patient last visit) ]
    Changes from baseline in pro-inflammatory cytokine (IL6)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prospective Study in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 Infection
Official Title  ICMJE A Prospective, Controlled, Randomized, Multicenter Study to Compare the Efficacy of a Chloroquine Analog (GNS561), an Anti-PD-1 (Nivolumab), an Anti-NKG2A (Monalizumab), an Anti-interleukine-6 Receptor (Tocilizumab) and an Anti-C5aR (Avdoralimab) Versus Standard of Care in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 (COVID-19) Infection.
Brief Summary

A prospective, controlled, randomized, multicenter study whose goal is to compare the efficacy of a chloroquine analog (GNS561), an anti PD-1 (nivolumab), an anti-NKG2A (monalizumab), an anti-C5aR (avdoralimab) 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 anti-NKG2A vs standard of care (randomization ratio 1:1:1:1).
  • COHORT 2 (moderate/severe symptoms): GNS561 vs anti-IL6 vs anti-C5aR vs standard of care (randomization ratio 1:1:1:1).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
  • COHORT 1 : Patients with mild symptoms or asymptomatic
  • COHORT 2 : Patients with moderate/severe symptoms
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • SARS-CoV-2 (COVID-19) Infection
  • Advanced or Metastatic Hematological or Solid Tumor
Intervention  ICMJE
  • Drug: Chloroquine analog (GNS651)

    Cohort 1 (arm B): 200mg bid loading dose for 2 days then, 200 qd orally for 14 consecutive days.

    Cohorte 2 (arm E): 200mg bid loading dose for 2 days then, 200 qd/day orally, per os, for 14 consecutive days.

    If for any reason a treatment is not given within the allowed treatment window (± 12h) it will be cancelled (i.e., missed for that time point), and treatment will be resumed at the next dosing day.

  • Drug: Nivolumab
    Cohorte 1 (arm C): 0.3mg/Kg, intravenously, single infusion at Day 1.
  • Drug: Tocilizumab
    Cohorte 2 (arm F): 400mg flat dose, intravenously, single infusion at Day 1.
  • Other: Standard of care

    In cohorts 1 and 2, patients allocated in the standard of care arms should receive best supportive care, as per the investigator's discretion and the local routine practices. With regards to the respiratory symptoms and medical resoures at investigational site, the following should be given according to the patient's condition: oxygen supplementation, non-invasive ventilation, invasive ventilation, antibiotherapy, vasopressor support, renal replacement therapy, or extracorporeal membrane oxygenation.

    Additional care and medications should be administered in the patient's best interest.

  • Drug: Avdoralimab
    Cohorte 2 (arm H): 500mg, intravenously, at Day 1 then 200mg once daily every 2 days during 14 Days
  • Drug: Monalizumab
    Cohorte 2 (arm G) : 50mg (flat dose),intravenously, single infusion at Day 1.
Study Arms  ICMJE
  • Experimental: Chloroquine analog (GNS651)
    Interventions:
    • Drug: Chloroquine analog (GNS651)
    • Other: Standard of care
  • Experimental: Anti-PD-1 (nivolumab)
    Interventions:
    • Drug: Nivolumab
    • Other: Standard of care
  • Experimental: Anti-IL-6 (tocilizumab)
    Interventions:
    • Drug: Tocilizumab
    • Other: Standard of care
  • Standard of care
    Intervention: Other: Standard of care
  • Experimental: anti-NKG2A (monalizumab)
    Interventions:
    • Other: Standard of care
    • Drug: Monalizumab
  • Experimental: anti-C5aR (avdoralimab)
    Interventions:
    • Other: Standard of care
    • Drug: Avdoralimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: June 5, 2020)
384
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2020)
273
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.; Nota Bene : A maximum time of 7 days may have elapsed between the date of first symptoms and the date of consent for patient cohort 1 (mild). In cohort 2 (severe), up to 10 days may have elapsed since the first symptoms.

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. Multidisciplinary approach that patient is 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 enrollment (in case of emergency situation, please refer to protocol section 12.1 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, anti-CTLA4 or anti-NKG2A.

E2. For cohort 2 only: Patient currently receiving therapy with an anti- IL-6 or anti-IL-6R or with an anti-C5aR.

E3. Contraindication to treatment with nivolumab or monalizumab (cohort 1 only) or to tocilizumab or avdoralimab (cohort 2 only) as per respective SPC and IB, 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 (quinine, chloroquine, tafenoquine, hydroxychloroquine, mefloquine). Patients previously exposed to CQ, HCQ or other quinoline derivates should have interrupted their treatment at least 72h prior to randomization.

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, including but not limited to :

  • Major surgery.
  • Azithromycine and chloroquine or any quinoline derivatives (quinine, chloroquine, tafenoquine, hydroxychloroquine, mefloquine)
  • 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 known active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening), known active hepatitis C (Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA at screening) or known 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04333914
Other Study ID Numbers  ICMJE ET20-076 - IMMUNONCOVID-20
2020-001373-70 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Centre Leon Berard
Study Sponsor  ICMJE Centre Leon Berard
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Philippe CASSIER Centre Leon Berard
PRS Account Centre Leon Berard
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP