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

NCT03352934 | Completed Phase 2

• 2 other identifiers: 2016-0072016-004373-40
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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.

Conditions

Cancer

Keywords

avelumab; anti-PD-L1; neuroendocrine tumor; NET G3; neuroendocrine carcinoma; NEC G3

Outcome Measures

Primary Outcomes (1)

• disease control rate (DCR) after 16 weeks of avelumab treatment

  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.

  16 weeks

Secondary Outcomes (9)

• disease control rate (DCR) on other assessments

  8, 24, 36, 48, 60 weeks

• Objective response rate (ORR) on every assessment

  8, 16, 24, 36, 48, 60 weeks

• Best overall response (BOR)

  8, 16, 24, 36, 48, 60 weeks

• Duration of disease control

  up to 1 year

• Time to response (TTR)

  up to 1 year

Other Outcomes (4)

• assessment of serum levels in Chromatogranin A (CgA)

  0, 8, 16, 24, 36, 48, 60 weeks

• assessment of serum levels in Neuron specific enolase (NSE)

  0, 8, 16, 24, 36, 48, 60 weeks

• Tumor growth rate (TGR)

  0, 8, 16, 24, 36, 48, 60 weeks

Study Arms (1)

Avelumab

EXPERIMENTAL

10 mg/kg Avelumab every 2 weeks

Drug: Avelumab

Interventions

Avelumab DRUG

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.

Also known as: MSB0010718C, anti-PD-L1

Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
• 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)

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (4)

Poliklinik für Innere Medizin I Universitätsklinikum Halle

Halle, D-06120, Germany

Location

Nationales Centrum für Tumorerkrankungen Universitätsklinikum Heidelberg

Heidelberg, D-69120, Germany

Location

Schwerpunkt Endokrinologie und Stoffwechselerkrankungen Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, D-55131, Germany

Location

Klinik für Innere Medizin, Abteilung Gastroenterologie Universitätsklinikum Gießen und Marburg

Marburg, D35043, Germany

Location

MeSH Terms

Conditions

Neoplasms; Neuroendocrine Tumors; Carcinoma, Neuroendocrine

Interventions

avelumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Study Officials

• Matthias M Weber, MD

  Johannes Gutenberg University Mainz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 3, 2017
• First Posted: November 24, 2017
• Study Start: December 7, 2017
• Primary Completion: February 18, 2022
• Study Completion: February 18, 2022
• Last Updated: February 25, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)