Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
Condition: Recurrent Pituitary Adenomas
MeSH terms: Adenoma; Pituitary Neoplasms; Pituitary Diseases; Recurrence
Intervention: Capecitabine; Temozolomide
Intervention description: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14.; 150 to 200 mg/m2 orally on days 10 through 14.
Intervention MeSH terms: Capecitabine; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is an open label study to assess the efficacy of capecitabine (CAP) and temozolomide
      (TMZ) in recurrent pituitary adenomas. There will be a safety run-in of at least three
      patients to establish any dose limiting toxicities. Enrolled patients will receive treatment
      in 28-day cycles: capecitabine 1500mg/m2 per day (divided into two doses with maximum daily
      dose of 2500mg) on days 1 through 14 and oral temozolomide 150 to 200 mg/m2 on days 10
      through 14. This will be followed by 14 days off treatment. MRI imaging will be completed
      after every two cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of
      disease progression or unacceptable toxicity.
    

Eligibility criteria:

        Inclusion Criteria::

          -  Male or female ≥ 18 years of age.

          -  Patients with nonfunctioning tumors must have histologically confirmed pituitary
             adenoma. Patients with functioning tumors do not require surgery if there is clear
             diagnosis of functioning pituitary adenomas established based on endocrine evaluation.

          -  Karnofsky performance status ≥ 70%.

          -  Life expectancy of greater than six months.

          -  Residual or recurrent pituitary adenoma ≥1cm in maximal diameter on MRI Brain; patient
             must have received at least one prior therapy, such as surgery, radiation and/or
             medical therapy.

          -  Patients must have normal organ and marrow function as defined below. NOTE: Laboratory
             values must be taken within 7 days prior to chemotherapy administration. Transfusions
             and/or growth factor support may not be used to meet this criteria):

          -  Platelet count ≥ 100 × 109/L.

          -  Hemoglobin ≥ 9 g/dL.

          -  WBC ≥ 3 × 109/L

          -  Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.

          -  Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 x ULN if Gilbert's disease
             is documented.

          -  Aspartate transaminase (AST) ≤ 2.5 ULN.

          -  Alanine transaminase (ALT) ≤ 2.5 ULN.

          -  Serum creatinine ≤ 1.5 × ULN OR creatinine clearance≥60mL/min/1.73 m2 for patients
             with creatinine levels above institutional normal.

          -  Patients must be able to undergo a MRI Brain/Pituitary

          -  For women of child-bearing potential and for men with partners of child-bearing
             potential, subject must agree to take contraceptive measures for duration of treatment
             and at least 6 months after the last dose of chemotherapy.

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

          -  Prior temozolomide and/or capecitabine therapy for treatment of the pituitary tumor.

          -  Other active malignancy outside of nonmelanoma skin cancer (patients in remission and
             with prior treatment more than two years ago will be accepted into trial).

          -  Clinically significant renal, hematologic or hepatic abnormalities.

          -  Use of Vitamin K antagonists such as warfarin (concentrations may be altered by
             concomitant use of capecitabine)

          -  Uncontrolled concurrent illness including, but not limited to, ongoing or active
             infection requiring IV antibiotics & psychiatric illness/social situations that would
             limit compliance with study requirements

          -  History of deficient dihydropyrimidine dehydrogenase activity.

          -  History of immunodeficiency.

          -  Patients who are taking any other concurrent investigational therapy.

          -  Patients who are pregnant or breastfeeding.

          -  Patients who have had prior radiation treatment in the last six months

          -  Patients who have had prior pituitary surgery within the last two months