A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors
A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors
This randomized phase II trial studies how well giving temozolomide with or without capecitabine works in treating patients with advanced pancreatic neuroendocrine tumors. Drugs used in chemotherapy, such as temozolomide and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether temozolomide is more effective with or without capecitabine in treating patients with advanced pancreatic neuroendocrine tumors.
PRIMARY OBJECTIVES:
I. To evaluate progression-free survival (PFS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.
SECONDARY OBJECTIVES:
I. To evaluate response rates (RR) associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.
II. To evaluate overall survival (OS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.
III. To evaluate the toxicity associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.
IV. To evaluate the usefulness of methyl guanine methyltransferase (MGMT) status (by immunohistochemistry [IHC] and promoter methylation) for predicting response in pancreatic neuroendocrine tumor patients treated with either temozolomide or temozolomide and capecitabine.
V. To bank radiology images for evaluation of quality, reproducibility, and compliance with computed tomography (CT) methodology.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive capecitabine PO twice daily (BID) on days 1-14 and temozolomide PO QD on days 10-14. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.
Inclusion Criteria:
Patient must have histologically or pathologically confirmed locally unresectable or metastatic low or intermediate grade pancreatic neuroendocrine tumor
Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; baseline measurements and evaluations of all sites of disease must be obtained <= 4 weeks prior to randomization and must be acquired by multiphasic CT or contrast magnetic resonance imaging (MRI)
Date of last documented disease progression must be within 12 months from date of randomization
Prior everolimus and/or sunitinib therapy is allowed, so long as it was discontinued >= 4 weeks prior to randomization
Concurrent somatostatin analogues are allowed provided that patients
Chemoembolization is allowed if ≥ 4 weeks from study entry. There are 2 possible scenarios:
Leukocytes >= 3,000/mm^3
Absolute neutrophil count >= 1,500/mm^3
Hemoglobin >= 9 g/dL
Platelets >= 100,000/mm^3
Total bilirubin <= institutional upper limit of normal (ULN) or <= 1.5 X institutional ULN (if the patient has liver metastases)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) <= 3 X institutional ULN or (<= 5 X institutional ULN if the patient has liver metastases)
Serum creatinine <= 1.5 X institutional ULN
Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Patient must have life expectancy >= 12 weeks all females of childbearing potential must have a blood test or urine study within =< 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
Patient must be able to swallow pills
Patient must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol
Exclusion Criteria:
Small cell carcinoma
Prior temozolomide, dacarbazine (DTIC), or capecitabine, or 5-FU (fluorouracil) therapy
Receiving any other investigational agents while on study treatment
Receiving Coumadin while on treatment; other anticoagulants are allowed
Patients with either clinically apparent central nervous system metastases or carcinomatous meningitis are ineligible
Active or uncontrolled infection or serious medical or psychiatric illness
History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine
Absorption issues that would limit the ability to absorb study agents
Patients with a history of the following within 12 months of study entry:
Symptomatic peripheral vascular disease
Patients with previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:
Pregnant or breast-feeding
Orange, California 92868, United States
Jacksonville, Florida 32207, United States
Miami, Florida 33136, United States
Highland Park, Illinois 60035, United States
Ann Arbor, Michigan 48106, United States
Jefferson City, Missouri 65109, United States
Springfield, Missouri 65802, United States
Mount Holly, New Jersey 08060, United States
Lewisburg, Pennsylvania 17837, United States
Greenville, South Carolina 29615, United States