Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas (TMZ-Cap)

• ClinicalTrials.gov Identifier: NCT03930771
• Recruitment Status: Recruiting
• Last Update Posted: December 24, 2020
• Sponsor: Weill Medical College of Cornell University
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Recurrent Pituitary Adenomas	Drug: Capecitabine; Drug: Temozolomide	Phase 2

Study Design

• Study Type: Interventional
• Estimated Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
• Actual Study Start Date: May 21, 2019
• Estimated Primary Completion Date: September 1, 2023
• Estimated Study Completion Date: September 1, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: All Patients; All subjects will receive: Capecitabine (oral 5-Fluorouracil) 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14.; Temozolomide (second generation alkylating agent) 150 to 200 mg/m2 orally on days 10 through 14. After completion of 6 cycles, patients achieving a complete or partial tumor response may continue to receive capecitabine temozolomide at the investigator's discretion in the absence of disease progression or unacceptable toxicity. Patients will be monitored for six months after they come off the study (either after completing 6 cycles or in setting of disease progression or unacceptable toxicity).

Drug: Capecitabine; 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14.; Drug: Temozolomide; 150 to 200 mg/m2 orally on days 10 through 14.

Outcome Measures

Primary Outcome Measures :

1. Number of subjects with Radiographic Response, as defined by the RECIST criteria. [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. Effect of the CAP and TMZ combination on pituitary function, measured by changes in pituitary hormone secretion in patients [ Time Frame: At baseline and every 8 weeks, up to 6 months ]
   Serum prolactin, IGF-1, ACTH, FSH, LH and TSH levels are used to assess changes in pituitary hormone function. These tests will only be repeated if found to be abnormal at baseline.
2. Safety, as measured by the number of subjects with at least one AE [ Time Frame: 6 months ]
3. Tolerability of the TMZ and Capecitabine combination, as measured by number of participants with a dose-limiting toxicity [ Time Frame: 6 months ]
4. Tumor invasiveness and aggressiveness, determined by assessing the relationship between select indicators with response to chemotherapy, time to progression, and tumor invasiveness. [ Time Frame: 6 months ]
   Tumor invasiveness and aggressiveness, determined by assessing the relationship between select indicators (including Ki67 nuclear labelling index, p53 expression, MGMT expression/methylation status, and additional tumor genetic profiling) with response to chemotherapy, time to progression, and tumor invasiveness (based on the Knosp criteria).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Victoria Dai, RN; (646) 962-2185; vid9053@med.cornell.edu

Locations

United States, New York

Weill Cornell Medical College; Recruiting

New York, New York, United States, 10065

Contact: June Greenberg jdg2002@med.cornell.edu

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

• Principal Investigator: Rajiv Magge, MD; Weill Medical College of Cornell University

More Information

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03930771
• Other Study ID Numbers: 1809019558
• First Posted: April 29, 2019
• Last Update Posted: December 24, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Pituitary Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Brain Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Adenoma; Pituitary Diseases; Hypothalamic Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Capecitabine; Temozolomide; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents