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    Summary
    EudraCT Number:2020-002715-21
    Sponsor's Protocol Code Number:AIO-KRK-0220
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-02-26
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2020-002715-21
    A.3Full title of the trial
    Perioperative/Adjuvant atezolizumab in patients with MSI-high or MMR-deficient stage III colorectal cancer ineligible for oxaliplatin-based chemotherapy– a Phase II study (ANTONIO)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Perioperative/Adjuvant atezolizumab in patients with MSI-high or MMR-deficient stage III colorectal cancer ineligible for oxaliplatin-based chemotherapy– a Phase II study
    A.3.2Name or abbreviated title of the trial where available
    ANTONIO
    A.4.1Sponsor's protocol code numberAIO-KRK-0220
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAIO-Studien-gGmbH
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.4.1Name of organisation providing supportImmodulon Therapeutics Ltd.
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAIO-Studien-gGmbH
    B.5.2Functional name of contact pointAIO-Studien-gGmbH
    B.5.3 Address:
    B.5.3.1Street AddressKuno-Fischer-Str. 8
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code14057
    B.5.3.4CountryGermany
    B.5.4Telephone number004930814534462
    B.5.5Fax number004930322932926
    B.5.6E-mailaio.regulatory@aio-studien-ggmbh.de
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tecentriq (R)
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAtezolizumab
    D.3.2Product code L01XC32
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNATEZOLIZUMAB
    D.3.9.1CAS number 1380723-44-3
    D.3.9.4EV Substance CodeSUB178312
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tecentriq (R)
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAtezolizumab
    D.3.2Product code L01XC32
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNATEZOLIZUMAB
    D.3.9.1CAS number RO5541267
    D.3.9.4EV Substance CodeSUB178312
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIMM-101
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntradermal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIMM-101
    D.3.9.3Other descriptive nameIMM-101
    D.3.9.4EV Substance CodeSUB33966
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeIMM-101 is an immunotherapeutic agent containing heat-killed whole cell Mycobacterium obuense National Collection of Type Cultures (NCTC) 13365
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with MSI-high or MMR-deficient stage III colorectal cancer who are ineligible for or who refuse oxaliplatin-based chemotherapy after R0 tumor resection (main study) or planned resection (sub-study)
    E.1.1.1Medical condition in easily understood language
    patients with stage III colon or rectum cancer who are ineligible or refuse oxaliplatin-based chemotherape after surgical removal of the tumor (main study) oder the surgery is planned (sub-study)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10009955
    E.1.2Term Colon cancer stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10009966
    E.1.2Term Colon carcinoma stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 22.0
    E.1.2Level PT
    E.1.2Classification code 10078672
    E.1.2Term DNA mismatch repair protein gene mutation
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10080676
    E.1.2Term Microsatellite instability
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10001167
    E.1.2Term Adenocarcinoma of colon
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10001171
    E.1.2Term Adenocarcinoma of colon stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10061451
    E.1.2Term Colorectal cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10010034
    E.1.2Term Colorectal cancer stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10052360
    E.1.2Term Colorectal adenocarcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10007446
    E.1.2Term Carcinoma of rectum
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10007450
    E.1.2Term Carcinoma of rectum stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10007468
    E.1.2Term Carcinoma rectum stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    main study: To determine whether atezolizumab alone ( or atezolizumab combined with IMM-101, patient enrolled in arm B before May 31st 2023) can significantly improve disease-free survival rate at 3 years compared to historical control when used as adjuvant treatment in patients with MSI-H/dMMR stage III colorectal cancer for whom oxaliplatin regimens are not a viable treatment option

    sub-study: To assess the efficacy of perioperative atezolizumab (with IMM 101, patient enrolled in substudy before May 31st 2023) in patients with MSI-high clinical stage III colorectal cancer for whom oxaliplatin regimens are not a viable treatment option in terms of pathological complete (pCR) or subtotal (<10% vital tumor cells) regression after 5 weeks of neoadjuvant treatment
    E.2.2Secondary objectives of the trial
    main study: Determine whether atezolizumab monotherapy or atezolizumab combined with IMM-101 show promising efficacy (DFS and overall survival) compared to historical control when used as adjuvant treatment in patients with MSI-H/dMMR stage III colon or rectal cancer for whom oxaliplatin regimens are not a viable treatment option.
    To assess the safety and tolerability profile of atezolizumab with or without IMM-101 in patients with MSI-high stage III colorectal cancer for whom oxaliplatin regimens are not a viable treatment option
    To determine the impact of atezolizumab with or without IMM-101 on patient-reported outcomes and health-related QoL, and functional domains of health-related QoL.
    sub-study: To asses efficacy in terms of disease-free survival and overall survival.
    To assess safety, tolerability, and QoL of perioperative atezolizumab with IMM 101 in patients with MSI-high clinical stage III colorectal cancer for whom oxaliplatin regimens are not a viable treatment option.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
    2. Male or female ≥ 18 years of age
    3. Histologically confirmed adenocarcinoma of the colon or rectum
    4. For the main study: Pathological Stage III disease For the perioperative sub-study: Clinical stage III disease
    5. For the main study: R0-resected primary tumor For the perioperative sub-study: Resectable primary tumor; R0 resection anticipated (R1-resected patients can remain on study.)
    6. Tumor is MSI-high (MSI-H) or MMR-deficient (dMMR) For the main study: assessed from biopsy or from resected tumor tissue For the perioperative sub-study: assessed from biopsy
    7. ECOG status 0 – 2
    8. Ineligible for oxaliplatin-based adjuvant chemotherapy or patient’s refusal of oxaliplatin-based adjuvant chemotherapy
    9. Adequate blood count, liver enzymes, and renal function – re-testing can be undergone once in case of initial results near cutoff
    - White blood cell count ≥ 3.5 x 106/mL
    - Platelet count ≥ 100 x 109/L (>100,000 per mm3)
    - Hemoglobin ≥ 9 g/dL (blood transfusion > 2 weeks before testing is permitted)
    - AST (SGOT)/ALT (SGPT) ≤ 5 x institutional upper limit of normal
    - Serum Creatinine ≤ 1.5 x institutional ULN and a calculated glomerular filtration rate ≥ 30 mL per minute
    10. Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and PTT < 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of registration
    11. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
    12. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly-effective contraception (i.e., one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for up to 6 months after the last dose of study drug.
    E.4Principal exclusion criteria
    1. Severe infection within 4 weeks prior to registration e.g. hospitalization for complications of infection, bacteremia, known active pulmonary disease with hypoxia, or severe pneumonia or any active infection requiring systemic therapy within 4 weeks prior to registration. Patients with positive test result for SARS-CoV2 should be managed as per local institutional guidelines
    2.For the main study: Distant metastases or residual disease/For the perioperative sub-study: Distant metastases or macroscopic residual disease (R2 resection status)
    3. Neoadjuvant radiotherapy or radio-chemotherapy (rectal cancer patients without prior radio- or radio-chemotherapy allowed); prior neoadjuvant radio-chemotherapy or radiotherapy for rectal cancer is allowed if >5 years and secondary colorectal cancer
    4. Prior adjuvant chemotherapy for colorectal cancer; allowed if >5 years and secondary colorectal cancer
    5. Prior treatment with atezolizumab or any other checkpoint inhibitor
    6. Prior exposure to IMM-101
    7. Treatment with systemic immunosuppressive medication within 2 weeks prior to treatment start, or anticipation of need for systemic immunosuppressive medication during study treatment
    8. Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment.
    9. History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins.
    10. Known hypersensitivity to CHO cell products or any component of the atezolizumab formulation.
    11. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. If any of these lung diseases is suspected based on the patient’s history or the integrated evaluation of clinical and radiological records, an additional spirometry should be conducted.
    12. Active HBV infection (chronic or acute), defined as having a positive HBsAg test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total HBcAb test at screening followed by a negative HBV DNA test, are eligible for the study. The HBV DNA test will be performed only for patients who have a positive total HBcAb test. Patients are also eligible if HBV DNA < 500 IU/mL obtained within 28 days prior to initiation of study treatment, AND anti-HBV treatment for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
    13 Anti-viral therapy against HCV during the trial (allowed prior to trial)
    14. Positive HIV test. As an exception, known HIV+ patients may be included if they have: A stable regimen of HAART; No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests
    15. a) Treatment with a live, attenuated vaccine within 4 weeks prior to first dose of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the last dose of study treatment. b) Treatment with any vaccine during screening and the first cycle of treatment.
    16. Active tuberculosis
    17. Active or history of autoimmune disease or immune deficiency e.g. myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
    18. Prior (<3 years) or concurrent malignancy that either progresses or requires active treatment. Exceptions: basal cell cancer of the skin, pre-invasive cancer of the cervix, T1a or T1b prostate carcinoma, superficial urinary bladder tumor
    19. History of hypersensitivity to any of the study drugs or any excipient IMM-101
    20. History of allergic reaction to any mycobacterial product
    21. Prior allogeneic stem cell or solid organ transplantation requiring immunosuppressive therapy or other major immunosuppressive therapy
    22. Severe non-healing wounds, ulcers or bone fractions
    23. Evidence of bleeding diathesis or coagulopathy
    24. Major gastrointestinal bleeding within 4 weeks prior to treatment start, unless cause of bleeding was resected tumor
    25. Major surgical procedures other than primary tumor resection, except open biopsy, nor significant traumatic injury within 28 days prior to registration, or anticipation of the need for major surgical procedure during the course of the study except for surgery of central intravenous line placement for chemotherapy administration.
    26. Medication that is known to interfere with any of the agents applied in the trial.
    E.5 End points
    E.5.1Primary end point(s)
    For the main study: The primary efficacy endpoint is disease-free survival (DFS) rate at 3 years, defined as the proportion of patients without relapse or tumor-related death from any cause 3 years after start of treatment in the intention-to-treat population.

    For the sub-study: Pathological complete (pCR) or subtotal (<10% vital tumor cells) regression (measured in resected tumors) after completion of 5 weeks of neoadjuvant treatment.

    Safety endpoints
    Safety endpoints in both the main study and the sub-study are the incidence, severity and causality/ relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI).
    Severity will be assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 5.0 (CTCAE v5.0).
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint 3-year DFS rate is defined as the proportion of patients being alive without recurrent disease 3 years after surgery in the ITT population.
    Each arm will be analyzed separately according to the ITT principle (i.e. include all patients who received at least 1 dose of study treatment).
    To facilitate a PP analysis, the formal sample size is inflated by 8% to yield 50 patients in patient group with atezolizumab only (Arm A) per treatment arm as the accrual goal for the main study. Arm B (patient group with atezolizumab plus IMM101) will be closed with 10 patients.
    Patients with/without IMM-101 will be evaluated together. A subgroup analysis is planned.
    E.5.2Secondary end point(s)
    For the main study:
    ▪ DFS including 1-, and 2-year tumor-specific DFS rates
    ▪ Overall Survival (OS) including 1-, 2- and 3-year OS rates

    Exploratory endpoints
    ▪ Rate of patients without detectable ctDNA after 12 months. ctDNA-free is defined as a ctDNA level below the lowest limit of detection of the respective Liquid Biopsy Assay
    ▪ Quality of life, assessed by EORTC QLQ-C30 and PRO-CTCAE questionnaires

    Safety endpoints
    Safety endpoints in both the main study and the sub-study are the incidence, severity and causality/ relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI).
    Severity will be assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 5.0 (CTCAE v5.0).

    In addition, all efficacy, safety and exploratory endpoints of the main study will also be assessed for the sub-study.

    E.5.2.1Timepoint(s) of evaluation of this end point
    All other efficacy and safety parameters will be evaluated in an explorative or descriptive manner, providing proportions, means, medians, ranges, standard deviations and/or confidence intervals, or Kaplan-Meier estimates, as appropriate.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    single arm, open, neoadjuvant/adjuvant treatment
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned40
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months54
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state80
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients will be treated according to standard-of-care at the discretion of the investigator
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-08-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-10-22
    P. End of Trial
    P.End of Trial StatusOngoing
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