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

NCT ID: NCT04333914

Last Updated: 2022-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-15
• Study Completion Date: 2021-12-31

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).

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Autophagy inhibitor (GNS651)

Group Type: EXPERIMENTAL

Autophagy inhibitor (GNS651)

Intervention Type: DRUG

Cohort 1 (arm B): 200mg q.d. orally for 10 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.

Standard of care

Intervention Type: OTHER

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.

Standard of care

Group Type: OTHER

Standard of care

Intervention Type: OTHER

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.

anti-NKG2A (Monalizumab)

Group Type: EXPERIMENTAL

Standard of care

Intervention Type: OTHER

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.

Monalizumab

Intervention Type: DRUG

Cohorte 2 (arm G) : 50mg (flat dose),intravenously, single infusion at Day 1.

anti-C5aR (Avdoralimab)

Group Type: EXPERIMENTAL

Standard of care

Intervention Type: OTHER

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.

Avdoralimab

Intervention Type: DRUG

Cohorte 2 (arm H): 500mg, intravenously, at Day 1 then 200mg once daily every 2 days during 14 Days

Interventions

Autophagy inhibitor (GNS651)

Cohort 1 (arm B): 200mg q.d. orally for 10 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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Avdoralimab

Cohorte 2 (arm H): 500mg, intravenously, at Day 1 then 200mg once daily every 2 days during 14 Days

Intervention Type: DRUG

Monalizumab

Cohorte 2 (arm G) : 50mg (flat dose),intravenously, single infusion at Day 1.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

I1. Age 18 or older at the time of enrolment for women and age 60 or older at the time of enrolment for men.

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) without indication of transfer in a rescucitation unit.; 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).

Note: Item cancelled (addendum 2 - October 2020)

I6. Life-expectancy longer than 3 months.

I7. Adequate bone marrow and end-organ function defined by the following laboratory results:

• Bone marrow:

• Hemoglobin ≥ 9.0 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/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 1) 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 1) 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-NKG2A.

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

E3. Patient presents a contraindication to monalizumab treatment (cohort 1 only) or to avdoralimab (cohort 2 only) as per respective IB, including known hypersensitivity to one of these study drugs or severe hypersensitivity reaction to any monoclonal antibody.

E4. For cohort 1 only: Patient known to have intolerance or hypersensitivity to chloroquine or any quinoline derivatives (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 received 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
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Leon Berard

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Virginie AVRILLON, M.D.

Role: PRINCIPAL_INVESTIGATOR

Centre Leon Berard

Jean-Yves BLAY, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Centre Leon Berard

Locations

Centre Léon Bérard

Lyon, Rhône, France

Centre Jean Perrin

Clermont-Ferrand, , France

CHU Clermont Ferrand

Clermont-Ferrand, , France

Centre Oscar Lambret

Lille, , France

AP-HP Hôpital Saint Antoine

Paris, , France

AP-HP La Pitié Salpétrière

Paris, , France

Hôpital Saint-Joseph

Paris, , France

AP-HP Tenon

Paris, , France

AP-HP Hôpital Bichat Claude Bernard

Paris, , France

GH Diaconesses Croix Saint Simon

Paris, , France

Institut de cancérologie Strasbourg Europe (ICANS)

Strasbourg, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

Other Identifiers

2020-001373-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ET20-076 - IMMUNONCOVID-20

Identifier Type: -

Identifier Source: org_study_id