Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors
Condition: Gastrinoma; Glucagonoma; Insulinoma; Islet Cell Carcinoma; Pancreatic Polypeptide Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma
MeSH terms: Carcinoma; Neuroendocrine Tumors; Insulinoma; Carcinoma, Islet Cell; Gastrinoma; Glucagonoma; Somatostatinoma
Intervention: temozolomide; capecitabine
Intervention description: Given PO; Given PO
Intervention MeSH terms: Capecitabine; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 144.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: temozolomide; capecitabine; pancreatic neuroendocrine tumor

Summary:

      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.
    

Eligibility criteria:

        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

               -  Have been on a stable dose for 8 weeks and

               -  Have documented disease progression on that dose

          -  Chemoembolization is allowed if ≥ 4 weeks from study entry. There are 2 possible
             scenarios:

               -  If patient has hepatic disease only: they need to have progressed in the liver
                  since chemoembolization and have measurable disease by RECIST 1.1 in order to be
                  eligible.

               -  If patient has hepatic and extrahepatic disease: they will need to have
                  progressed inside OR outside the liver and have measureable disease by RECIST 1.1
                  in order to be eligible.

          -  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:

               -  Has not undergone a hysterectomy or bilateral oophorectomy; or

               -  Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
                  has had menses at any time in the preceding 24 consecutive months)

          -  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:

               -  Arterial thromboembolic events

               -  Unstable angina

               -  Myocardial Infarction

          -  Symptomatic peripheral vascular disease

          -  Patients with previous or concurrent malignancy; exceptions are made for patients who
             meet any of the following conditions:

               -  Non-melanoma skin cancer, in situ cervical cancer, or breast cancer in situ OR

               -  Prior malignancy completely excised or removed and patient has been continuously
                  disease free for > 5 years OR

               -  Prior malignancy cured by non-surgical modalities and patient has been
                  continuously disease free for > 5 years

          -  Pregnant or breast-feeding