Capecitabine, Temozolomide, and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors
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|ClinicalTrials.gov Identifier: NCT01525082|
Recruitment Status : Completed
First Posted : February 2, 2012
Results First Posted : December 30, 2020
Last Update Posted : May 4, 2021
|Condition or disease||Intervention/treatment||Phase|
|Gastrinoma Glucagonoma Insulinoma Pancreatic Polypeptide Tumor Recurrent Islet Cell Carcinoma Recurrent Pancreatic Cancer Somatostatinoma Stage III Pancreatic Cancer Stage IV Pancreatic Cancer||Drug: Capecitabine Drug: Temozolomide Biological: Bevacizumab||Phase 2|
- Estimate if the combination of capecitabine and temozolomide with bevacizumab for metastatic or unresectable neuroendocrine tumors will improve response rate (RR) by 62% over historical controls (null RR of 40% to true RR 65%).
- Assess the toxicities using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
- Evaluate progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier analysis.
- Assess O6-methyl guanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) at baseline by central pathology (path) review.
- Assess serum hormone marker levels.
- Evaluate computed tomography (CT) Perfusion as a tool to predict early therapeutic response. (Optional)
- Bank serum for future correlative analyses.
Patients receive bevacizumab intravenously (IV) over 30 to 90 minutes on days 1 and 15, capecitabine orally (PO) twice daily (BID) on days 1 to 14, and temozolomide PO once daily (QD) on days 10 to 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity, with assessment for treatment effect every 3 cycles.
After completion of study treatment, patients are followed up patients are followed long-term for survival.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Capecitabine, Temozolomide, and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors|
|Study Start Date :||December 2012|
|Actual Primary Completion Date :||January 2018|
|Actual Study Completion Date :||December 31, 2019|
Experimental: Bevacizumab + Capecitabine + Temozolomide
Cycles repeat every 28 days until disease progression, unacceptable toxicity, or withdrawal.
Capecitabine by mouth twice daily on Days 1 to 14
Temozolomide by mouth daily on Days 10 to 14
Bevacizumab IV over 30 to 90 minutes on Days 1 & 15
- Radiographic Response (RR) [ Time Frame: 18 months ]
Tumor response to treatment with the combination of capecitabine & temozolomide plus bevacizumab in patients with metastatic or unresectable pancreatic neuroendocrine tumors was assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions. Response is defined as:
- Complete Response (CR) = Disappearance of all target lesions
- Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions
- Overall Response (OR) = CR + PR
- Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)
- Stable disease (SD) = Small changes that do not meet any of the above criteria
The outcome is reported as the number of participants who between 3 and 18 months after treatment initiation achieve CR, PR, or clinical response (PR + CR), each a number without dispersion.
- Treatment-related Toxicity [ Time Frame: 18 months ]Patients will be monitored for hematologic (blood and lymphatic), gastrointestinal (stomach and gut), renal (kidney), liver (metabolic), neurological, and systemic (constitutional) toxicities (treatment-related adverse events). Toxicity events occurring during treatment will be tabulated for each indicated organ system, and listed separated for serious and non-serious events, with the toxicity attribution indicated. The outcome is reported as the number of events, a number without dispersion.
- Progression-free Survival (PFS) [ Time Frame: 82 months ]Progression-free survival (PFS) means the length of time that participants survive without disease (tumor) progression, and was assessed using Kaplan-Meier analysis. The outcome is given as the mean in months with standard error of the mean.
- Overall Survival (OS) [ Time Frame: 82 mo ]
Time from the date of enrollment to the date of death due to any cause or the last date the patient was known to be alive (censored observation) at the date of data cutoff for the final analysis. The results will be reported as median in months
The length of overall survival (OS) of participants was assessed by Kaplan-Meier analysis. The outcome is given as the median in months with full range.
- O6-methylguanine DNA Methyltransferase (MGMT) Status by Immunohistochemistry (IHC) [ Time Frame: 18 months ]
O6-alkylguanine DNA alkyltransferase is a protein that in humans is encoded by the gene "O6-methylguanine DNA methyltransferase" (MGMT). Deficiency of the gene product, ie, the protein, is refereed to as "MGMT deficiency," and is thought to be predictive of response to temozolomide and is more often associated with pancreatic NETs.
MGMT status in pre-treatment biopsy specimens was to be assessed by immuno-histochemistry (IHC), and associated to best clinical response. The outcome is reported by the the number of patients that were IHC-positive (MGMT detected) or IHC-negative (MGMT not detected), and by best clinical response [ie, complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD)]. The outcome is reported as a number without dispersion.
- O6-methylguanine DNA Methyltransferase (MGMT) by Promoter Methylation [ Time Frame: 18 months ]
O6-alkylguanine DNA alkyltransferase is a protein that in humans is encoded by the gene "O6-methylguanine DNA methyltransferase" (MGMT). Deficiency of the gene product, ie, the protein, is refered to as "MGMT deficiency," and is thought to be predictive of response to temozolomide and is more often associated with pancreatic NETs.
MGMT status in pre-treatment biopsy specimens was to be assessed by extent of genetic promoter methylation (an analysis of DNA), and correlated to subject survival.
MGMT status in pre-treatment biopsy specimens was to be assessed by promoter methylation assessment (PM), and associated to best clinical response. The outcome is reported by the the number of patients that were PM-positive (MGMT detected) or PM-negative (MGMT not detected), and by best clinical response [ie, complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD)]. The outcome is reported as a number without dispersion.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01525082
|United States, California|
|Stanford University Medical Center|
|Stanford, California, United States, 94305|
|Principal Investigator:||Shaheen Shagufta, MD||Stanford University|