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Avelumab Treatment in Patients With Neuroendocrine Carcinomas (NEC G3) Progressive After Chemotherapy (AveNEC)

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ClinicalTrials.gov Identifier: NCT03352934
Recruitment Status : Recruiting
First Posted : November 24, 2017
Last Update Posted : August 28, 2019
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
Prof. Dr. Matthias M. Weber, Johannes Gutenberg University Mainz

Brief Summary:
The purpose of the AveNEC trial is to investigate the clinical activity and safety of avelumab in patients with NEC G3 (WHO 2010), including "NET G3" who are progressive after first line chemotherapy.

Condition or disease Intervention/treatment Phase
Cancer Drug: Avelumab Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-label, Multicenter Trial to Investigate the Clinical Activity and Safety of Avelumab in Patients With Advanced, Metastatic High Grade Neuroendocrine Carcinomas NEC G3 (WHO 2010) Progressive After Chemotherapy
Actual Study Start Date : December 7, 2017
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Avelumab
10 mg/kg Avelumab every 2 weeks
Drug: Avelumab
Avelumab will be administered as intravenous infusion at 10 mg/kg once every two weeks until documented disease progression (PD), unacceptable toxicity, or any criterion for treatment withdrawal are met.
Other Names:
  • MSB0010718C
  • anti-PD-L1




Primary Outcome Measures :
  1. disease control rate (DCR) after 16 weeks of avelumab treatment [ Time Frame: 16 weeks ]
    The primary endpoint is the disease control rate (DCR) after 16 weeks of avelumab treatment. DCR is defined as the percentage of subjects with a confirmed reduction in tumor size compared to baseline (complete response (CR) and partial response (PR)) as well as fulfilling the criteria for stable disease (SD) according RECIST1.1.


Secondary Outcome Measures :
  1. disease control rate (DCR) on other assessments [ Time Frame: 8, 24, 36, 48, 60 weeks ]
    Disease control rate (DCR) on other assessments. DCR is the proportion of patients with complete response, partial response and stable disease according to RECIST1.1.

  2. Objective response rate (ORR) on every assessment [ Time Frame: 8, 16, 24, 36, 48, 60 weeks ]
    Objective response rate (ORR) on every assessment. ORR is the proportion of patients with complete response (CR) or partial response (PR) according to RECIST1.1.

  3. Best overall response (BOR) [ Time Frame: 8, 16, 24, 36, 48, 60 weeks ]
    Best overall response (BOR). BOR is recorded from the start of the treatment until disease progression/recurrence according to RECIST1.1.

  4. Duration of disease control [ Time Frame: up to 1 year ]
    Duration of disease control: Duration of disease control is defined as the time from the first disease control (CR, PR, SD) to progression of disease (PD) according to RECIST1.1.

  5. Time to response (TTR) [ Time Frame: up to 1 year ]
    Time to response (TTR): TTR is the time from the first dose of trial medication to the first documentation of either complete response (CR) or partial response (PR) according to RECIST1.1.

  6. Median Progression-free survival time (PFS) [ Time Frame: up to 2 years ]
    Median Progression-free survival time (PFS). The time from first dose of trial medication to first documentation of objective tumor progression (PD) or to death due to any cause, whichever occurs first.

  7. Overall survival (OS) and survival rate after 1 and 2 years [ Time Frame: up to 2 years ]
    Overall survival (OS) and survival rate after 1 and 2 years: Overall survival is defined as the time from first dose of trial medication to date of death due to any cause. Survival rate is defined as rate of subjects surviving for at least 1 year or 2 years after first application of trial medication.

  8. Quality of life (QoL) [ Time Frame: 0, 8, 16, 24, 36, 48, 52, 60 weeks ]
    Quality of life (QoL) assessed by the EORTC QLQ-C30 questionnaire on Screening/Baseline, during Treatment on every assessment, on End of Treatment and on Safety FU visit

  9. Incidence of adverse events (AEs) [ Time Frame: 60 weeks ]
    Reporting of number and frequency of adverse Events (AEs) during treatment with avelumab and until Safety Follow


Other Outcome Measures:
  1. assessment of serum levels in Chromatogranin A (CgA) [ Time Frame: 0, 8, 16, 24, 36, 48, 60 weeks ]
    assessment of serum levels in Chromatogranin A (CgA) measured at time of tumor assessments

  2. assessment of serum levels in Neuron specific enolase (NSE) [ Time Frame: 0, 8, 16, 24, 36, 48, 60 weeks ]
    assessment of serum levels in and Neuron specific enolase (NSE) measured at time of tumor assessments

  3. Tumor growth rate (TGR) [ Time Frame: 0, 8, 16, 24, 36, 48, 60 weeks ]
    Tumor growth rate (TGR): TGR is the percentage change in tumor volume over one month

  4. Tumor response according to irRECIST [ Time Frame: 8, 16, 24, 36, 48, 60 weeks ]
    Tumor response according to irRECIST



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects aged ≥ 18 years
  • Histologically proven neuroendocrine neoplasia NEC G3 (WHO 2010)
  • One block or 20 slides (cut at 4 microns) of archival tumor tissue, if available, to perform biomarker assessment
  • No curative option available
  • Progressive disease within 9 months before study Initiation and after at least one chemotherapy (platinum based chemotherapy or STZ/TEM/DTIC based chemotherapy in NET G3)
  • Presence of measurable disease as per RECIST1.1 criteria
  • Physiologic function:

    • Hematologic: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused)
    • Hepatic: total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 × ULN for subjects with documented metastatic disease to the liver)
    • Renal: estimated creatinine clearance ≥ 60 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
  • Pregnancy and contraception:

    • Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential.
    • Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 30 days for female and 90 days for male patients after avelumab treatment if the risk of conception exists.
  • ECOG Performance Status 0 - 2
  • Written informed consent: Signed and dated informed consent of the subject must be available before start of any specific trial procedures
  • Ability of subject to understand nature, importance and individual consequences of clinical trial.

Exclusion Criteria:

  • Merkel Cell carcinoma (MCC) or small cell lung cancer (SCLC)
  • Typical or Atypical Carcinoid of the lung with a Ki67 < 20%
  • Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints)
  • Neuroendocrine tumors that are potentially curable by surgery
  • Major surgery within 4 weeks of initiation of study medication.
  • TACE, TAE, SIRT or PRRT within 3 months of starting study treatment
  • Patients pretreated with Interferon as last treatment line prior to study entry
  • Concurrent anticancer treatment after the start of trial treatment (e.g., cyto-reductive therapy, TKI therapy, mTOR inhibitor therapy, radiotherapy [with the exception of palliative radiotherapy], immune therapy, or cytokine therapy except for erythropoietin or use of any investigational drug).
  • Immunosuppressants: Current use of immunosuppressive medication, EXCEPT for the following:

    1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
    2. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
    3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Prior organ transplantation, including allogeneic stem cell transplantation
  • Active infection requiring systemic therapy
  • HIV/AIDS: Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Hepatitis: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
  • Autoimmune disease: Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
  • Pregnancy or lactation
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Vaccination: Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
  • Hypersensitivity to study drug: Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
  • Cardiovascular disease: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  • Participation in other clinical trials during the present clinical trial or within the last 30 days or five terminal phase half-lives of the drug whichever is longer, prior to baseline (this also includes investigational formulation of market products).
  • Medical or psychological conditions that would jeopardise an adequate and orderly completion of the trial.
  • Patients, who are legally institutionalized

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03352934


Contacts
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Contact: Matthias M Weber, MD 00496131 ext 177260 mmweber@uni-mainz.de
Contact: Christian Fottner, MD 00496131 ext 177260 christian.fottner@unimedizin-mainz.de

Locations
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Germany
Klinik für Endokrinologie & Stoffwechselerkrankungen Universitätsklinikum Essen Not yet recruiting
Essen, Germany, D45147
Contact: Harald Lahner, MD    0049201 ext 723 6405    harald.lahner@uni-due.de   
Contact: Nicole Unger, MD       nicole.unger@uk-essen.de   
Poliklinik für Innere Medizin I Universitätsklinikum Halle Recruiting
Halle (Saale), Germany, D-06120
Contact: Sebastian Krug, MD    0049345 ext 557 2665    sebastian.krug@medizin-uni-halle.de   
Contact: Patrick Michl, MD       patrick.michl@uk-halle.de   
Nationales Centrum für Tumorerkrankungen Universitätsklinikum Heidelberg Recruiting
Heidelberg, Germany, D-69120
Contact: Leonidas A Apostolidis, MD    00496221 ext 56 5982    leonidas.apostolidis@med.uni-heidelberg.de   
Contact: Eva Winkler, MD       eva.winkler@med.uni-heidelberg.de   
Schwerpunkt Endokrinologie und Stoffwechselerkrankungen Universitätsmedizin der Johannes Gutenberg-Universität Mainz Recruiting
Mainz, Germany, D-55131
Contact: Matthias M Weber, MD    0049 6131 ext 177260    mmweber@unimedizin-mainz.de   
Contact: Christian Fottner, MD    0049 6131 ext 177260    christian.fottner@unimedizin-mainz.de   
Klinik für Innere Medizin, Abteilung Gastroenterologie Universitätsklinikum Gießen und Marburg Recruiting
Marburg, Germany, D35043
Contact: Anja Rinke, MD    00496421 ext 58 65968    sprengea@uni-marburg.de   
Contact: Vanessa Petry, MD    00496421 ext 58 66460      
Sponsors and Collaborators
Johannes Gutenberg University Mainz
Merck KGaA, Darmstadt, Germany
Investigators
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Principal Investigator: Matthias M Weber, MD Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. Medizinische Klinik und Poliklinik, Abteilung Endokrinologie und Stoffwechselkrankheiten, D-55131 Mainz, Germany

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Responsible Party: Prof. Dr. Matthias M. Weber, Principal Investigator, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier: NCT03352934     History of Changes
Other Study ID Numbers: 2016-007
2016-004373-40 ( EudraCT Number )
First Posted: November 24, 2017    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof. Dr. Matthias M. Weber, Johannes Gutenberg University Mainz:
avelumab
anti-PD-L1
neuroendocrine tumor
NET G3
neuroendocrine carcinoma
NEC G3
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Neuroendocrine
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs