Safety and Tolerability of Everolimus as Second-line Treatment in Poorly Differentiated Neuroendocrine Carcinoma / Neuroendocrine Carcinoma G3 (WHO 2010) and Neuroendocrine Tumor G3 - an Investigator Initiated Phase II Study

NCT02113800 | Completed Phase 2

• 3 other identifiers: AIO-NET-0112CRAD001KDE55T2012-004550-28
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed as an open-label, prospective, single arm, multicenter study of everolimus in histologically confirmed, neuroendocrine carcinoma G3 /neuroendocrine tumor G3 after failure of first-line platin-based chemotherapy (open-label pilot study). The aim of this study is to provide a second line therapy to patients with any type of platinum based first line chemotherapy, to gather data on disease control rate and progression free survival.

Conditions

Poorly Differentiated Malignant Neuroendocrine Carcinoma; Neuroendocrine Carcinoma, Grade 3; Neuroendocrine Carcinoma, Grade 1 [Well-differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Carcinoma, Grade 2 [Moderately Differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Tumor, Grade 3 and Disease Progression as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (AEs)

  Incidence of adverse events (AEs) overall and by severity, and serious adverse events (SAEs). Severity will be assessed using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) for Adverse Events, version 4.03 (CTCAEv4.03). To evaluate tolerability and safety of everolimus in second-line treatment of poorly differentiated neuroendocrine carcinoma / neuroendocrine carcinoma G3 according to WHO 2010 and neuroendocrine tumors G3.

  approx. 18 month

Secondary Outcomes (11)

• Progression free survival (PFS)

  approx. 18 month

• Objective response rate (ORR)

  approx. 18 month

• Disease control rate (DCR)

  approx. 18 month

• Duration of response (DR)

  approx. 18 month

• Overall Survival (OS)

  approx. 18 month

Study Arms (1)

Single Arm

EXPERIMENTAL

Patients receive Everolimus orally, 10 mg/day. The end of study will be performed when tumor progression has been observed for 28 patients. Patients who are still under treatment at that time may continue with chemotherapy at the discretion of the investigator, but will be excluded from the study.

Drug: Everolimus (Afinitor®)

Interventions

Everolimus (Afinitor®) DRUG

Formulation: 10 mg/day Route: oral (tablet)

Single Arm

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Male or female ≥ 18 years of age
• Patients with poorly differentiated neuroendocrine carcinoma, neuroendocrine carcinoma G3 (NEC - G3 according to WHO 2010) or well or moderately differentiated neuroendocrine carcinoma (NET - G1 / G2) that switched to G3 (confirmed by histology) or neuroendocrine tumor G3 (NET G3) and disease progression as measured by RECIST 1.1
• Progression during or after treatment with first-line platinbased chemotherapy. In NET G3 that switched from NET G2 the line of therapy is determined from the time of revised histology (confirming a G3 NEN)
• Measurable disease according to RECIST 1.1
• Performance Status according to Eastern Cooperative Oncology Group (ECOG) status 0 - 2 (Karnofsky Performance status ≥ 80%)
• Women of child-bearing potential must have a negative pregnancy test
• Laboratory requirements:
• Hematology
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 10\^9/L
• Leukocyte count ≥ 3.0 x 10\^9/L
• Hemoglobin ≥ 9 g/dL or 5.59 mmol/L
• Hepatic Function
• Total bilirubin ≤ 1.5 time the upper limit normal (ULN)

You may not qualify if:

• Known or suspected allergy or hypersensitivity reaction to any of the components of study treatment or their excipients.
• Previous therapy with mTOR inhibitor
• Radiotherapy :
• Concurrent radiotherapy involving target lesions used for this study.
• Concurrent palliative radiation (but radiation for non-target lesions is allowed if other target lesions are available outside the involved field)
• previous pre-operative or post-operative radiotherapy within 3 months before study treatment
• History of other malignant tumors within the last 5 years, except basal cell carcinoma or curatively excised cervical carcinoma in situ
• Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment
• Inadequate pulmonary function according to the Investigator's judgment, history of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
• Known active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or HIV infection
• Serious concomitant disease or medical condition that in the judgment of the investigator renders the patient at high risk from treatment complication
• Any systemic disease requiring oral intake of corticosteroids (except for replacement therapy of corticosteroids - hydrocortisone in case of adrenal or pituitary insufficiency)
• Hearing loss ≥ Grade 3 (CTCAE v4.03)
• Patient pregnant or breast feeding, or planning to become pregnant within 8 weeks after the end of treatment

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Assign Data Management and Biostatistics GmbH: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Charité-Universitätsmedizin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Related Publications (1)

• Jungels C, Deleporte A. State of the art and future directions in the systemic treatment of neuroendocrine neoplasms. Curr Opin Oncol. 2021 Jul 1;33(4):378-385. doi: 10.1097/CCO.0000000000000740.

  PMID: 33973550 DERIVED

Related Links

• Working Group for Medical Oncology (AIO) from the German Cancer Society (DKG)

MeSH Terms

Conditions

Carcinoma, Neuroendocrine; Lymphoma, Follicular; Neuroendocrine Tumors

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Marianne Pavel, Prof. Dr.

  Charité-Universitätsmedizin

  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: SPONSOR

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 15, 2014
• Study Start: August 1, 2015
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: October 28, 2020

Record last verified: 2020-10

Locations

DE (1)