Capecitabine and Temozolomide for Neuroendocrine Cancers
Condition: Neuroendocrine Tumors
MeSH terms: Neuroendocrine Tumors; Carcinoma, Neuroendocrine
Intervention: Capecitabine; Temozolomide
Intervention description: Capecitabine 1500 mg/m2/day (PO divided BID) with a maximum daily dose of 2500mg Two week treatment regimen followed by two weeks off treatment, repeated for 12 cycles
After patients have completed 12 cycles with no signs of progression of disease, radiologic evaluation (CT or MRI) will be done after three cycles. This will result in two 28 day cycles and one 35 day cycle.; Temozolomide 150-200 mg/m2/day (PO divided BID).
Two week treatment regimen followed by two weeks off treatment, repeated for 12 cycles
After patients have completed 12 cycles with no signs of progression of disease, radiologic evaluation (CT or MRI) will be done after three cycles. This will result in two 28 day cycles and one 35 day cycle.
Intervention MeSH terms: Capecitabine; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Pancreatic cancer; Neuroendocrine tumors; Carcinoid tumors; Pheochromocytomas; Gastrinomas; Zollinger-Ellison syndrome; MEN Type I/II; Somatostatinomas; VIPomas; Merkel cell tumors; medullary thyroid carcinoma

Summary:

      This phase II study is designed to assess whether treatment with capecitabine/temozolomide
      (CAP/TEM) is safe and effective in treating subjects with progressive, differentiated,
      metastatic neuroendocrine tumors (NET). The primary objective of the study is to determine
      the radiologic response rate to this regimen in progressive, metastatic, differentiated
      neuroendocrine cancers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a tissue diagnosis of any of the following metastatic, well or
             moderately differentiated, slow growing neuroendocrine tumor and must demonstrate
             progressive metastatic disease by prior serial computerized tomography (CT) or
             magnetic resonance imaging (MRI) scans, or have increased symptoms from their tumors
             while on sandostatin LAR or octreotide.

          -  Carcinoid tumors originating anywhere in the body including the gastrointestinal (GI)
             tract or bronchial tree

          -  Pancreatic neuroendocrine tumors (including functional and non-functional islet cell,
             insulinomas and glucagonomas)

          -  Pheochromocytomas, gastrinomas (Zollinger-Ellison Syndrome), multiple endocrine
             neoplasia (MEN) Type I/II, paragangliomas, adrenal carcinomas with NET markers by
             immunohistochemistry (IHC) or serum.

          -  Somatostatinoma, VIPoma, Merkel Cell tumors, medullary thyroid carcinoma

          -  Neuroendocrine tumors of unknown primary site

          -  Any other tumors with differentiated neuroendocrine features may be included such as
             aggressive pituitary adenomas/carcinomas, which are neuroendocrine in origin

          -  Patients must have progressed on octreotide therapy (up to and including Sandostatin
             LAR-60 mg/month) and/or radioactive isotopes linked to octreotide or its congeners if
             they has a positive octreotide scan. Patients who have negative or mildly positive
             octreotide scans are exempt from this requirement. Exceptions to this requirement are
             patients who have NETs in the pituitary gland. Sandostatin does not cross into the
             pituitary blood supply well.

          -  Measurable disease: Any primary and/or metastatic mass reproducibly measurable in one
             or two diameters by Response Evaluation Criteria In Solid Tumors (RECIST) parameters
             by CT scan or MRI scan.

          -  Ineligible for other high priority national or institutional studies

          -  Prior radiation and surgery allowed: ≥3 weeks since surgery or chemotherapy or hepatic
             embolization/chemoembolization or radioactive isotopes (i.e. Yttrium 90) ≥4 weeks
             since radiation therapy (RT)

          -  Non pregnant females, not in menopause, who are not breast feeding with a negative
             serum β-HCG (human chorionic gonadotropin) test within 1 week of starting the study.
             Men and women of childbearing potential must consent to using effective barrier
             contraception while on treatment and for 2 months thereafter.

        Exclusion Criteria:

          -  Prior chemotherapy with capecitabine or temozolomide. Patients previously treated with
             continuous infusion 5-FU or any schedule of DTIC (dacarbazine), which are similar to
             capecitabine and temozolomide, respectively, will be excluded. Patients can have had
             prior therapies up to 3 prior chemotherapy regimens such as bolus 5-FU, streptozocin,
             anthracyclines, Camptothecin-11 (CPT-11), etoposide, or a platinum agent

          -  Hypersensitivity: Patients with a history of severe hypersensitivity reaction to
             capecitabine, 5-FU, temozolomide or DTIC will be excluded (i.e. anaphylaxis or
             anaphylactoid reactions)

          -  Serious medical or psychiatric illness preventing informed consent or intensive
             treatment (e.g, serious infection)

          -  Patients with tumor which has spread to the central brain (cerebral/cerebellum) and
             spinal cord.

          -  Patients with compromised immune systems are at increased risk of toxicity and lethal
             infections when treated with marrow-suppressive therapy. Therefore, HIV-positive
             patients are excluded from the study

          -  Prior malignancies in the last 5 years other than; curatively treated carcinoma
             in-situ previously treated with curative intent (cancer free for the past year)