Clinical trial NCT03930771: Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
Official title: Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Pituitary Adenomas
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2019-04-29
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Number of Subjects With Radiographic Response, as Defined by the RECIST Criteria.
timeFrame: 6 months
Secondary outcomes:
measure: Effect of the CAP and TMZ Combination on Pituitary Function, Measured by Changes in Pituitary Hormone Secretion in Patients
timeFrame: At baseline and every 8 weeks, up to 6 months
measure: Safety, as Measured by the Number of Subjects With at Least One AE
timeFrame: 6 months
measure: Tolerability of the TMZ and Capecitabine Combination, as Measured by Number of Participants With a Dose-limiting Toxicity
timeFrame: 6 months
measure: Tumor Invasiveness and Aggressiveness, Determined by Assessing the Relationship Between Select Indicators With Response to Chemotherapy, Time to Progression, and Tumor Invasiveness.
timeFrame: 6 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Rajiv Magge, MD
role: PRINCIPAL_INVESTIGATOR
References: