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    Summary
    EudraCT Number:2016-002522-36
    Sponsor's Protocol Code Number:CPDR001E2201
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-06-17
    Trial results View 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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2016-002522-36
    A.3Full title of the trial
    An open label phase II study to evaluate the efficacy and safety of PDR001 in patients with advanced or metastatic, well-differentiated, non-functional neuroendocrine tumors of pancreatic, gastrointestinal (GI), or thoracic origin or poorly-differentiated gastroenteropancreatic neuroendocrine
    carcinoma (GEP-NEC), that have progressed on prior treatment
    Studio in aperto, di Fase II per valutare l¿efficacia e la sicurezza d¿impiego di PDR001 in pazienti con tumori neuroendocrini ben differenziati non funzionanti in stadio avanzato o metastatico, di origine pancreatica, gastrointestinale (GI) o toracica o carcinoma neuroendocrino gastroenteropancreatico scarsamente differenziato (GEP-NEC), in progressione al trattamento precedente
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An open label phase II study to find out if the drug PDR001 is safe and has beneficial effects in patient who have advanced or metastatic nonfunctional
    neuroendocrine tumors of pancreatic, gastrointestinal, thoracic origins or poorly-differentiated gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) and have progressed on prior treatment
    Studio di valutazione dell¿efficacia e della sicurezza d¿impiego di PDR001 in pazienti con tumori neuroendocrini ben differenziati non funzionanti in stadio avanzato o metastatico, di origine pancreatica, gastrointestinale (GI) o toracica o GEP-NEC scarsamente differenziato
    A.3.2Name or abbreviated title of the trial where available
    -
    -
    A.4.1Sponsor's protocol code numberCPDR001E2201
    A.5.4Other Identifiers
    Name:-Number:-
    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 SponsorNOVARTIS PHARMA AG
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNOVARTIS FARMA S.p.A
    B.5.2Functional name of contact pointDrug Regulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressLargo Umberto Boccioni, 1
    B.5.3.2Town/ cityORIGGIO
    B.5.3.3Post code21040
    B.5.3.4CountryItaly
    B.5.4Telephone number0296541
    B.5.5Fax number029659066
    B.5.6E-mailinfo.studiclinici@novartis.com
    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 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 namePDR001
    D.3.2Product code PDR001
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    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 INNPDR001
    D.3.9.2Current sponsor codePDR001
    D.3.9.3Other descriptive namePDR001
    D.3.9.4EV Substance CodeSUB171710
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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.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
    Advanced neuroendocrine tumor (NET) of pancreatic, GI or lung origin
    -
    E.1.1.1Medical condition in easily understood language
    Advanced neuroendocrine cancer of gastrointestinal or pancreatic or lung origin
    -
    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 10052399
    E.1.2Term Neuroendocrine tumour
    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
    Part 1
    To estimate the antitumor activity of PDR001 as a single agent in the
    well-differentiated NET and poorly differentiated GEP-NEC groups.
    Part 2
    To estimate the antitumor activity of
    PDR001 as a single agent in the
    expanded well-differentiated NET
    cohorts
    -
    E.2.2Secondary objectives of the trial
    Key secondary (part 1 and part 2 for
    expanded cohort(s))
    - To estimate efficacy of PDR001
    - To assess the safety and tolerability of PDR001
    - To evaluate additional efficacy
    parameters
    - To evaluate biochemical response to treatment (based on CgA and
    NSE) in the well-differentiated NET and poorly-differentiated GEP-NEC
    groups
    - To characterize the pharmacokinetics of PDR001 with 400 mg flat dose
    Q4W in the well differentiated NET and poorlydifferentiated GEP-NEC
    groups
    - To characterize patient's healthrelated quality of life with PDR001 in
    the well-differentiated NET and poorly-differentiated GEP-NEC groups
    - To evaluate the prevalence and incidence of immunogenicity in the
    well-differentiated NET and poorlydifferentiated GEP-NEC groups
    -.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients eligible for inclusion in this study have to meet all of the following criteria:
    1. Written informed consent must be obtained prior to any screening procedures
    2. Adult males or females = 18 years at screening.
    3. Pathologically confirmed, advanced (unresectable or metastatic):
    - Well-differentiated (G1 or G2) based on local pathology report, , non-functional
    neuroendocrine tumor of GI, pancreatic or thoracic (including lung and thymus) origin.
    - Poorly-differentiated GEP-NEC based on local pathology report
    4. No active symptoms related to carcinoid syndrome during the last 3 months prior to start of study treatment.
    5. Patients must have received prior treatment for advanced disease:
    - Well-differentiated NET group:
    a. Thoracic (lung and thymus origin) cohort:
    - Thymus origin: at least one prior systemic therapy according to investigator’s choice
    - Lung origin: at least one prior systemic therapy is required, which must include everolimus.
    b. GI cohort: at least two prior systemic regimens, which must include everolimus. Prior systemic therapies may include: somatostatin analogs, PRRT, and/or chemotherapy.
    c. pNET cohort: at least two prior systemic regimens, which must include everolimus and/or sunitinib. Prior systemic therapies may include: somatostatin analogs, PRRT and/or chemotherapy.
    Note: For well-differentiated NET, Prior treatment with interferon alpha is allowed provided that it is not the last treatment received prior to study entry.
    - Poorly-differentiated GEP-NEC group: at least one prior chemotherapy regimen according to Investigator’s choice.
    6. Radiological documentation of disease progression:
    - Well-differentiated NET group: Disease progression while on/or after the last treatment, and this progression must have been observed within 6 months prior to start of study treatment (i.e. maximum of 24 weeks from documentation of progression until study entry). Disease must show evidence of radiological disease progression based on scans performed not more than 12 months apart.
    - Poorly-differentiated GEP-NEC group: Disease progression while on or after prior treatment.
    7. At least one measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
    Note: Any lesions which have been subjected to percutaneous therapies or radiotherapy should not be considered measurable, unless the lesion has clearly progressed since the procedure.
    8. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
    9. Tumor biopsy material must be provided for all patients for the purpose of biomarker analysis:
    - Well-differentiated (G1/2) NET: Biopsy material must be provided following the diagnosis of metastatic disease. The tumor sample must be collected from a metastatic site not previously irradiated and should preferably be taken within 6 months but not more than 24 months prior to start of study treatment.
    - Poorly-differentiated GEP-NEC: Biopsy material must be collected from the primary tumor or from a metastatic site not previously irradiated, taken not more than 24 months prior to start of study treatment.
    10. Women of childbearing potential must have had a negative serum pregnancy test within 72 hours prior to the start of study treatment. Highly effective contraception must be used while on study.
    11. Patient is deemed by the investigator to have the ability and means to be compliant with the protocol (treatment and follow-up).
    12. Patient must meet the following laboratory values at the screening visit:
    - Absolute Neutrophil Count =1.5 x 109/L
    - Platelets =75 x 109/L
    - Hemoglobin (Hgb) =9 g/dL
    - Serum creatinine <1.5 mg/dL
    - Total bilirubin =1.5 x ULN
    - Aspartate transaminase (AST) = 3.0 x ULN, except for patients with liver metastasis, if AST =5.0 x ULN
    - Alanine transaminase (ALT) = 3.0 x ULN, except for patients with liver metastasis, if ALT =5.0 x ULN
    13. Patients enrolled in Part 2: life expectancy of at least 3 months
    -
    E.4Principal exclusion criteria
    1. Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell
    carcinoma.
    2. Pretreatwith interferon as last treatment prior to start of study treatment
    3. Prior treatment for study indication
    4. Systemic chronic steroid therapy (= 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment.
    5. Any untreated central nervous system (CNS) lesion.
    6. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents = 2 weeks prior to the first dose of study treatment.
    7. Malignant disease, other than that being treated in this study.
    8. Major surgery, open biopsy, or significant traumatic injury within 2 weeks prior to start of
    study treatment.
    9. Anticipation of the need for major surgical procedure during the course of the study
    10. Radiation therapy within 4 weeks prior to start of study treatment
    11. Hepatic intra-arterial embolization within the last 6 months.
    12. History of severe hypersensitivity reactions to other monoclonal antibodies
    13. Impaired cardiac function or clinically significant cardiac disease, including any of the
    following:
    14. Active, known or suspected autoimmune disease or a documented history of autoimmune
    disease, including ulcerative colitis and Crohn's disease
    15. Active infection requiring systemic antibiotic therapy.
    16. Known history of testing positive for Human Immunodeficiency Virus (HIV) infection.
    17. Patients with active Hepatitis B infection (HBsAg positive) will be excluded.
    18. Patients with positive test for hepatitis C ribonucleic acid (HCV RNA)..
    19. Any medical condition that would, in the investigator's judgment, prevent the patient's
    participation in the clinical study due to safety concerns, compliance with clinical study
    procedures or interpretation of study results.
    20. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
    21. Presence of = CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy, and ototoxicity, which are exclusion criteria if = CTCAE grade 3) due to prior cancer therapy.
    22. Not able to understand and to comply with study instructions and requirements.
    23. Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test within
    72 hours prior to initiating study treatment. Note: Low levels of hCG may also be considered a tumor marker, therefore if low hCG levels are detected, another blood sample at least 4 days later must be taken to assess the kinetics of the increase and transvaginal ultrasound must be performed to rule out pregnancy.
    -
    E.5 End points
    E.5.1Primary end point(s)
    Part 1
    ORR (confirmed PR and CR)
    according to blinded independent
    review committee (BIRC) radiological
    assessment by RECIST 1.1
    Part 2
    ORR (confirmed PR and CR) according
    to blinded independent review committee
    (BIRC) radiological assessment by
    RECIST 1.1
    -
    E.5.1.1Timepoint(s) of evaluation of this end point
    Imaging:
    Treatment Period: Every 8 weeks counting from Cycle 1 Day 1 for the first 13 cycles and then every 12 weeks from Cycle 13 Day1 thereafter
    EOT: If a scan was not conducted within 30 days prior to end of study
    treatment
    Efficacy follow-up: Continue same schedule as during treatment period until BIRC confirmed irRECIST progression
    -
    E.5.2Secondary end point(s)
    DoR by RECIST 1.1 and as per BIRC
    Frequency and severity of adverse events
    Other safety data as considered appropriate
    Disease Control Rate (DCR), Time to Response (TTR), PFS by RECIST 1.1 and as per BIRC
    Immune Response Criteria by irRECIST and as per BIRC (irORR,irDoR, irTTR, irDCR, irPFS)
    1-year and 2-year overall survival (OS) rate
    Changes from baseline in CgA and
    NSE
    PK parameters (e.g. Ctrough)
    Global health status/QOL score of the EORTC QLQ-C30 and the index score of the EQ-5D-5L
    Antidrug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment
    -
    E.5.2.1Timepoint(s) of evaluation of this end point
    Imaging:
    Treatment Period: Every 8 weeks counting from C1 D1 for the first 13 cycles and then every 12 weeks from C13 D1 thereafter
    EOT: If a scan was not conducted within 30 days prior to end of study treatment
    Efficacy f/u: until BIRC confirmed irRECIST progression PK/IG:
    Treatment period:
    At D1 of all cycles until C13 and D1 of every 6 cycles thereafter
    EOT 30-Day safety f/u
    Unscheduled:
    At the time of PD based on RECIST 1.1
    At the time of PD based on irRECIST
    PRO:
    Screening
    Treatment: Every 8 weeks from C3 D1 for the first 13 cycles and every 12 weeks from C13 D1 thereafter EOT 30-day safety follow-up
    Efficacy follow-up: Continue same schedule as during treatment period until BIRC confirmed irRECIST progression CgA/NSE:
    Screening
    Treatment: D1 of each cycle
    -
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open No
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA29
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    Israel
    Japan
    United States
    Austria
    Belgium
    France
    Germany
    Italy
    Netherlands
    Norway
    Spain
    Sweden
    Switzerland
    United Kingdom
    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: 'end of study' will be declared after all patients have discontinued study treatment and completed the safety follow-up period regardless of the efficacy follow-up.
    LPLS 'fine dello studio' sar¿ dichiarata dopo che tutti i pazienti hanno sospeso il trattamento e completato il peridodo di follow-up di sicurezza indipendentemente dell'efficacia del peridodo di follow-up.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days0
    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: 194
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 96
    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 state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 105
    F.4.2.2In the whole clinical trial 290
    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)
    Protocol: At the end of the study, every effort will be made to continue
    provision of investigational treatment outside this study through an
    alternative setting to patients who in the opinion of the Investigator
    are still deriving clinical benefit.
    ICF: After trial completion you will continue to be monitored as per
    standard clinical practice; if a new treatment is required your doctor
    will discuss with you the therapeutic options considered adequate to
    treat the disease.
    -
    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 Decision2017-03-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-12-21
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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