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

Primary Purpose

Recurrent Pituitary Adenomas

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Temozolomide
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Pituitary Adenomas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Weill Cornell Medical College

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All Patients

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Effect of the CAP and TMZ Combination on Pituitary Function, Measured by Changes in Pituitary Hormone Secretion in Patients
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.
Safety, as Measured by the Number of Subjects With at Least One AE
Tolerability of the TMZ and Capecitabine Combination, as Measured by Number of Participants With a Dose-limiting Toxicity
Tumor Invasiveness and Aggressiveness, Determined by Assessing the Relationship Between Select Indicators With Response to Chemotherapy, Time to Progression, and Tumor Invasiveness.
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).

Full Information

First Posted
April 25, 2019
Last Updated
July 15, 2022
Sponsor
Weill Medical College of Cornell University
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1. Study Identification

Unique Protocol Identification Number
NCT03930771
Brief Title
Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
Acronym
TMZ-Cap
Official Title
Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
the study had a low accrual rate
Study Start Date
May 21, 2019 (Actual)
Primary Completion Date
August 19, 2021 (Actual)
Study Completion Date
October 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Pituitary Adenomas

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All Patients
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
150 to 200 mg/m2 orally on days 10 through 14.
Primary Outcome Measure Information:
Title
Number of Subjects With Radiographic Response, as Defined by the RECIST Criteria.
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Effect of the CAP and TMZ Combination on Pituitary Function, Measured by Changes in Pituitary Hormone Secretion in Patients
Description
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.
Time Frame
At baseline and every 8 weeks, up to 6 months
Title
Safety, as Measured by the Number of Subjects With at Least One AE
Time Frame
6 months
Title
Tolerability of the TMZ and Capecitabine Combination, as Measured by Number of Participants With a Dose-limiting Toxicity
Time Frame
6 months
Title
Tumor Invasiveness and Aggressiveness, Determined by Assessing the Relationship Between Select Indicators With Response to Chemotherapy, Time to Progression, and Tumor Invasiveness.
Description
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).
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rajiv Magge, MD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas

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