Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas

NCT03930771 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 1809019558
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Pituitary Adenomas

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Radiographic Response, as Defined by the RECIST Criteria.

  Evaluation of Target lesions: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum onstudy (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  6 months

Secondary Outcomes (4)

• Effect of the CAP and TMZ Combination on Pituitary Function, Measured by Changes in Pituitary Hormone Secretion in Patients

  At baseline and every 8 weeks, up to 6 months

• Safety, as Measured by the Number of Subjects With at Least One AE

  6 months

• Tolerability of the TMZ and Capecitabine Combination, as Measured by Number of Participants With a Dose-limiting Toxicity

  6 months

• Tumor Invasiveness and Aggressiveness, Determined by Assessing the Relationship Between Select Indicators With Response to Chemotherapy, Time to Progression, and Tumor Invasiveness.

  6 months

Study Arms (1)

All Patients

EXPERIMENTAL

All subjects will receive: 1. Capecitabine (oral 5-Fluorouracil) 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. 2. 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; Drug: Temozolomide

Interventions

Capecitabine DRUG

1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14.

All Patients

Temozolomide DRUG

150 to 200 mg/m2 orally on days 10 through 14.

All Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Pituitary Neoplasms

Interventions

Capecitabine; Temozolomide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles

Limitations and Caveats

Due to lower accrual (N=1), there was insufficient data available in order to meet the primary and secondary outcome measures.

Results Point of Contact

• Title: Rajiv Magge
• Organization: Weill Cornell Medicine

ram9116@med.cornell.edu

212-746-6575

Study Officials

• Rajiv Magge, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2019
• First Posted: April 29, 2019
• Study Start: May 21, 2019
• Primary Completion: August 19, 2021
• Study Completion: October 1, 2021
• Last Updated: August 9, 2022
• Results First Posted: August 9, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)