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
Overview
- Phase
- Phase 2
- Intervention
- Everolimus (Afinitor®)
- Conditions
- Poorly Differentiated Malignant Neuroendocrine Carcinoma
- Sponsor
- AIO-Studien-gGmbH
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events (AEs)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Detailed Description
As more efficient drugs are urgently needed for the treatment of neuroendocrine tumors the investigator evaluated phosphorylated Mammalian target of rapamycin (mTOR) and effectors in a series of NEC G3 at the Charité Center. Everolimus showed antiproliferative effects in bronchial NET. In a second approach the data of this study should be the basis to generate another study to further explore everolimus as maintenance therapy in NEC G3/ NET G3.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Single Arm
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.
Intervention: Everolimus (Afinitor®)
Outcomes
Primary Outcomes
Incidence of adverse events (AEs)
Time Frame: approx. 18 month
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.
Secondary Outcomes
- Progression free survival (PFS)(approx. 18 month)
- Overall Survival (OS)(approx. 18 month)
- Disease control rate (DCR)(approx. 18 month)
- chromogranin A & B(approx. 12 month)
- neuron-specific enolase(approx. 12 month)
- Duration of response (DR)(approx. 18 month)
- Time to Progression (TTP)(approx. 18 month)
- progastrin releasing peptide(approx. 12 month)
- Objective response rate (ORR)(approx. 18 month)
- Correlation mTOR pathway components in tumor tissue to tumor response(approx. 18 month)
- Quality of life(approx. 18 month)