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出境医 / 临床实验 / Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas (TMZ-Cap)

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

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
Layout table for study information
Study Type : Interventional  (Clinical Trial)
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:

  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
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
Layout table for eligibility information
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
Layout table for location contacts
Contact: Victoria Dai, RN (646) 962-2185 vid9053@med.cornell.edu

Locations
Layout table for location information
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
Layout table for investigator information
Principal Investigator: Rajiv Magge, MD Weill Medical College of Cornell University
Tracking Information
First Submitted Date  ICMJE April 25, 2019
First Posted Date  ICMJE April 29, 2019
Last Update Posted Date December 24, 2020
Actual Study Start Date  ICMJE May 21, 2019
Estimated Primary Completion Date September 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2019) 		Number of subjects with Radiographic Response, as defined by the RECIST criteria. [ Time Frame: 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2020)
  • 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.
  • Safety, as measured by the number of subjects with at least one AE [ Time Frame: 6 months ]
  • Tolerability of the TMZ and Capecitabine combination, as measured by number of participants with a dose-limiting toxicity [ Time Frame: 6 months ]
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2019)
  • 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.
  • Safety, as measured by the number of subjects with at least one AE [ Time Frame: 6 months ]
  • Tolerability of the TMZ and Capecitabine combination, as measured by number of participants with a dose-limiting toxicity [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
Official Title  ICMJE Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Pituitary Adenomas
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: All Patients

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).

Interventions:
  • Drug: Capecitabine
  • Drug: Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 26, 2019) 		21
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2023
Estimated Primary Completion Date September 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Victoria Dai, RN (646) 962-2185 vid9053@med.cornell.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03930771
Other Study ID Numbers  ICMJE 1809019558
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Weill Medical College of Cornell University
Study Sponsor  ICMJE Weill Medical College of Cornell University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rajiv Magge, MD Weill Medical College of Cornell University
PRS Account Weill Medical College of Cornell University
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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