TEMCAP in Grade 3 and Low Ki-67 Gastroenteropancreatic Neuroendocrine Tumors

Study Overview
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Brief Summary
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GI tract including pancreas is the one of most common primary sites of neuroendocrine tumors. Current grading of neuroendocrine tumors are based on the 2010 WHO classification. This classifies grade 3 tumors as the neuroendocrine tumor with mitosis > 20 per 10 high power field or Ki-67 labeling index > 20%. Etoposide-based chemotherapy, mostly as the combination with cisplatin, has been the mainstay of the treatment for patients with grade 3 neuroendocrine tumors. However, a recent large retrospective analysis has suggested this regimen may not be effective in relatively low Ki-67 labeling index. Therefore, the investigators designed a clinical trial testing temozolomide-capecitabine combination, which has been mostly investigated in well differentiated (ie., grade 1 or 2) neuroendocrine tumors, in patients with grade 3 and low Ki-67 gastroenteropancreatic neuroendocrine tumors.

Official Title
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Phase 2 Study of Temozolomide Plus Capecitabine in Patients With Grade 3 and Low Ki-67 Gastroenteropancreatic Neuroendocrine Tumors

Conditions
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Neuroendocrine Tumors, Neuroendocrine Carcinoma, Temozolomide, Capecitabine

Intervention / Treatment
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* Drug: TEMCAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 19 years and older Histologically confirmed neuroendocrine tumors of gastrointestinal tract or pancreas Unresectable or metastatic disease Grade 3 according to the 2010 WHO classification (Ki-67 labeling index > 20% or > 20 mitoses per 10 high power field) Ki-67 labeling index < 60% At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0   2 Adequate bone marrow function as defined by platelets ≥ 100 x 109/L and neutrophils ≥ 1.5 x 109/L Adequate renal function, with serum creatinine < 1.5 x upper limit of normal (ULN) Adequate hepatic function with serum total bilirubin < 2 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other non life-threatening cancer (i.e., prostate or thyroid cancer) except where treated with curative intent > 5 years previously without evidence of relapse Written informed consent to the study Exclusion Criteria: Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy Obstruction of gastrointestinal tract Active gastrointestinal bleeding Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension) Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol Female subjects who are pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug. A highly effective method of contraception is defined as having a low failure rate (< 1% per year) when used consistently and correctly.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEMCAP<br>Temozolomide plus Capecitabine | Drug: TEMCAP<br>* Oral capecitabine 750 mg/m2 twice a day, Day 1 to 14 and oral temozolomide 200 mg/m2 once a day, Day 10 to 14<br>* Other names: Temozolomide and capecitabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Proportion of patients with complete or partial response graded by Response Evaluation Criteria in Solid Tumors version 1.1 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Time between the start of study treatment and disease progression | 2 years | 
| Overall survival | Time between the start of study treatment and survival | 2 years | 
| Toxicity (Adverse events graded by National Cancer Institute-Common Terminology Criteria version 4.03) | Adverse events graded by National Cancer Institute-Common Terminology Criteria version 4.03 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroendocrine tumors, Neuroendocrine Carcinoma, Capecitabine, Temozolomide