|- candidate number||21585|
|- NTR Number||NTR5041|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||16-jan-2015|
|- Secondary IDs||NL50842.031.14 |
|- Public Title||Phase II Study of cisplatin and everolimus in patients with metastatic or unresectable neuroendocrine carcinomas (NEC) of extrapulmonary origin|
|- Scientific Title||Phase II Study of cisplatin and everolimus in patients with metastatic or unresectable neuroendocrine carcinomas (NEC) of extrapulmonary origin|
|- Healt Condition(s) or Problem(s) studied||Metastasis, Neuroendocrine tumors, Extra pulmonary|
|- Inclusion criteria||1. Pathologically confirmed unresectable locally advanced NEC where no curative (chemoradiation) treatment options are available, and/or metastatic NECs of extrapulmonary origin as first line therapy NEC of extrapulmonary origin (WHO 2010 classification; Ki67 >20 %) including merkel cell carcinoma. |
2. Measurable disease according to RECIST 1.1, on CT-scan or MRI
3. ECOG Performance status 0-2 (see Appendix 2)
4. Adequate bone marrow function as shown by: ANC°›1.5 x 109/L, Platelets °›100 x 109/L, Hb >6 mmol/L
5. Adequate liver function as shown by:
Total serum bilirubin °‹1.5 ULN
ALT and AST °‹2.5x ULN (°‹5x ULN in patients with liver metastases)
6. Adequate renal function: calculated creatinin clearance > 60ml/min. (Cockcroft-Gault formula)
7. Life expectancy of at least 3 months.
8. Male or female age °› 18 years.
9. Signed informed consent.
10. Able to swallow and retain oral medication.
|- Exclusion criteria||1. Previous chemotherapy for metastatic or unresectable NEC of extrapulmonary origin. (prior peri-operative chemotherapy or chemoradiation for curative intention is allowed if at least 6 months have elapsed between completion of this therapy and enrolment into the study). |
2. Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus, everolimus)
3. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.
4. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) or cisplatin
5. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
6. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
7. Patients who have any severe and/or uncontrolled medical conditions such as: a. unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction °‹6 months prior to randomization, serious uncontrolled cardiac arrhythmia. b. active or uncontrolled severe infection, c. liver disease such as cirrhosis, decompensated liver disease, and known history chronic hepatitis d. known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air), e. active, bleeding diathesis;
8. Chronic treatment with corticosteroids or other immunosuppressive agents
9. Known history of HIV seropositivity
10. Pregnant or nursing (lactating) women
11. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 8 weeks after stopping study treatment.
12. Sexually active males, unless they use a condom during intercourse while taking study medication and for 8 weeks after stopping study medication.
13. History of documented congestive heart failure; angina pectoris requiring medication; evidence of transmural myocardial infarction on ECG; poorly controlled hypertension (systolic BP >180 mmHg or diastolic BP >100 mmHg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias.
14. Patients with dyspnoea at rest due to complications of advanced malignancy or other disease, or who require supportive oxygen therapy.
15. History or clinical evidence of brain metastases.
16. Any investigational drug treatment within 4 weeks of start of study treatment.
17. Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed if palliative radiotherapy given to bone metastastic site peripherally and patient recovered from any acute toxicity).
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||Single arm|
|- planned startdate ||1-apr-2015|
|- planned closingdate|
|- Target number of participants||39|
|- Interventions||everolimus and cisplatin|
|- Primary outcome||Primary endpoint of this study will be Disease Control Rate (DCR), defined as the sum of Overall Response Rate (ORR) consisting of Complete (CR), Partial Response Rate (PR) and stable disease (SD), all according to RECIST 1.1|
|- Secondary outcome||Secondary endpoints will be Time to relapse; Progression-free survival (PFS); Disease-free survival (DFS); Overall survival (OS); Effect on the markers chromogranin A (CgA) and neuron-specific enolase (NSE); Safety of everolimus in combination with cisplatin. |
|- Timepoints||Response to treatment will be assessed every 9 weeks and patients with stable disease or a better response will be allowed to continue protocol treatment up to 6 cycles . After this (combined) treatment, patients will be allowed to continue with single-agent everolimus until disease progression or unacceptable toxicity. All patients will be followed for toxicity, tumour progression and survival |
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES|| |
|- CONTACT for SCIENTIFIC QUERIES|| |
|- Sponsor/Initiator ||Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI AVL) |
(Source(s) of Monetary or Material Support)
|Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI/AVL)|
|- Brief summary|
|- Main changes (audit trail)|
|- RECORD||16-jan-2015 - 18-apr-2015|