EVINEC: Safety and Tolerability of Everolimus as second-line treatment in poorly differentiated neuroendocrine carcinoma / neuroendocrine carcinoma G3 according to WHO 2010 and neuroendocrine tumor G3 - an investigtor initiated Phase II study.

Phase 1

• Conditions: • Poorly differentiated neuroendocrine carcinoma, neuroendocrine carcinoma G3 (NEC G3 according to WHO 2010) with primary tumor outside lung• Well to moderately differentiated neuroendocrine carcinoma (NET G1/G2) that switched to G3 (confirmed by histology)• Neuroendocrine tumor G3 (NET G3); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004550-28-DE
• Lead Sponsor: AIO-Studien-gGmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10-14
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Signed written informed consent
2. Male or female =18 years of age
3. 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
4. Progression during or after treatment with first-line platin-based chemotherapy. In NET G3 that switched from NET G2 the line of therapy is determined from time of revised histology (confirming a G3 NEN)
5. Measurable disease according to RECIST 1.1
6. ECOG status 0-2 (Karnofsky Performance status =80%)
7. Women of child-bearing potential must have a negative pregnancy test
8. Laboratory requirements:
• Hematology
o Absolute neutrophil count =1.5x10^9/L
o Platelet count =100x10^9/L
o Leukocyte count =3.0x10^9/L
o Hemoglobin =9 g/dL or 5.59 mmol/l
• Hepatic Function
o Total bilirubin =1.5 time the upper limit normal (ULN)
o AST =3xULN in absence of liver metastases, or =5xULN in presence of liver metastases
o ALT =3xULN in absence of liver metastases, or =5xULN in presence of liver metastases
• Renal Function
o Creatinine clearance =50 mL/min according to Cockroft-Gault formula
• Metabolic Function
o Magnesium = lower limit of normal
o Calcium = lower limit of normal
o Others:
o CRP (PCT if CRP is elevated to exclude infection)
o negative urinary screening test for leucocytes and nitrite to exclude urinary tract infection (U - stix)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Known or suspected allergy or hypersensitivity reaction to any of the components of study treatment or their exipients.
2. Previous therapy with mTOR inhibitor
3.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
4. History of other malignant tumors within the last 5 years, except basal cell carcinoma or curatively excised cervical carcinoma in situ
5. Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
6. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =1year before enrolment
7. 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
8. Known active HBV, HCV or HIV infection
9. Serious concomitant disease or medical condition that in the judgment of the investigator renders the patient at high risk from treatment complication
10. Any systemic disease requiring oral intake of corticosteroids (except for replacement therapy of corticosteroids – hydrocortisone in case of adrenal or pituitary insufficiency)
11. Hearing loss = Grade 3 (CTCAE v4.03) 12. Patient pregnant or breast feeding, or planning to become pregnant within 8 weeks after the end of treatment
13. Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 8 weeks (male or female) after the end of treatment.
14. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 28 days prior to treatment start
15. Concurrent treatment with inhibitors (e.g. itraconazol, ketoconazol) and inducers (e.g. phenytoin, rifampicin) of CYP3A4 and/or the multidrug efflux pump P-glycoprotein (PgP).
16. Known drug abuse/alcohol abuse
17.Peripheral polyneuropathy = Grade 2 (CTCAE v4.03)
18. Active chronic inflammatory bowel disease
19. Any condition which might interfere with study objectives (e.g. infections) or would limit the patient’s ability to complete the study in the opinion of the investigator
20. Patient who has be incarcerated or involuntarily institutionalized by court order or the authorities (AMG § 40, Abs. 1 No. 4).
21. Affected persons who might be dependent on the sponsor or the investigator

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified