Study to Compare Capecitabine Combined With Dacarbazine(CAPDTIC) Versus Capecitabine Combined Temozolomide(CAPTEM) in Advanced and Metastatic Gastrointestinal Pancreatic and Esophageal Neuroendocrine Tumor

Study Overview
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Brief Summary
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The study will be conducted to compare the safety and efficacy of Capecitabine Combined With Dacarbazine(CAPDTIC) and Capecitabine Combined Temozolomide(CAPTEM) in advanced or metastatic gastrointestinal pancreatic and esophageal neuroendocrine tumor.In this prospective randomized phase II study, the investigators aim to compare the survival benefit as well as the safety forCapecitabine Combined With Dacarbazine(CAPDTIC) versus Capecitabine Combined Temozolomide(CAPTEM) in advanced or metastatic gastrointestinal pancreatic and esophageal neuroendocrine tumor.

Official Title
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A Randomized, Controlled Phase II Study to Compare Capecitabine Combined With Dacarbazine(CAPDTIC) Versus Capecitabine Combined Temozolomide(CAPTEM) in Advanced and Metastatic Gastrointestinal Pancreatic and Esophageal Neuroendocrine Tumor

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: Capecitabine, Dacarbazine
* Drug: Capecitabine, Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sign written informed consent form age ≥ 18 years pathologically confirmed well-differentiated neuroendocrine tumor; No prior antitumor treatment of capecitabine, dacarbazine or temozolomide. For recurrent patients after radical surgery, adjuvant chemotherapy should not include capecitabine, dacarbazine or temozolomide, and the last date should beyond 6 months prior to randomization; At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded) (routine CT scan >=20mm, spiral CT scan >=10mm, no prior radiation to measurable lesions); Screening laboratory values must meet the following criteria (within past 7 days): hemoglobin ≥ 9.0 g/dL; neutrophils ≥ 1500 cells/ μL; platelets ≥ 100 x 10^3/ μL; total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum creatinine ≤1╳ULN; KPS ≥ 70; Predicted survival >=3 months; Negative serum or urine pregnant test within 7 days prior to randomization for child-bearing age women; Sexually active males or females willing to practice contraception during the study until 30 days after end of study. Exclusion Criteria: Hypersensitivity to capecitabine, dacarbazine or temozolomide; Prior antitumor therapy (including corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment; Received surgery within past 4 weeks, or have not recovered from surgery; Severe diarrhea; Concurrent severe infection； Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including severe liver disease (active hepatitis, cirrhosis), uncontrolled diabetes or hypertension, or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm); Prior long term steroid therapy (excluding short term steroid treatment which is completed prior to > 2 weeks of study enrollment)； Meningeal carcinomatosis; Patients with central nervous system(CNS) disorder or peripheral nervous system disorder or psychiatric disease； Known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias and hypertension, or congestive heart failure, or cardiac infarction within 6 months prior to study enrollment, or cardiac insufficiency； Pregnant or nursing, or sexually active males or females refuse to practice contraception during the study until 30 days after end of study; History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible； Person with no capacity (legally) or inappropriate to continue study treatment for ethics/medical reasons； Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Capecitabine Combined With Dacarbazine(CAPDTIC)<br>patients in arm A will receive chemotherapy of CAPDTIC regimen: Capecitabine: 1000mg/m2 ，p.o. bid d1-14 q4W, Dacarbazine: 200mg/m2 ，iv drip,d1-5 q4W | Drug: Capecitabine, Dacarbazine<br>* Capecitabine: 1000mg/m2 ，p.o. bid d1-14 q4W Dacarbazine: 200mg/m2 ，iv drip,d1-5 q4W<br>|
| Experimental: B: Capecitabine Combined Temozolomide(CAPTEM)<br>patients in arm B will receive chemotherapy of CAPDTEM regimen: Capecitabine: 1000mg/m2 ，p.o. bid d1-14 q4W, Temozolomide: 200mg/m2 ，p.o.d10-14 q4W | Drug: Capecitabine, Temozolomide<br>* Capecitabine: 1000mg/m2 ，p.o. bid d1-14 q4W, Temozolomide: 200mg/m2 ，p.o. bid d10-14 q4W,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | CT/MRI will be performed every 2 cycles of treatment by RECIST 1.1 | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival is defined as the time from the date of first dose to the date of the first documented radiological progression or death due to any cause | baseline, every 8 weeks up to 1 year after last patient first treatment | 
| Overall survival | Overall survival is defined as the time from date of start of treatment to date of death due to any cause | baseline, every 8 weeks up to 1 year after last patient first treatment | 
| Incidence of Treatment-Emergent Adverse Events （Safety and Tolerability） | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemotherapy, OS, ORR, PFS, safety