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

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03930771
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 28.4
• Patients Per Site Per Month: 0

Study Details

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
• Actual Enrollment: 1 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
• Actual Primary Completion Date: Aug 19, 2021
• Actual Study Completion Date: Oct 1, 2021

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. [6 months]

   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

1. 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]

   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 [6 months]

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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medical College	New York	New York	United States	10065

Sponsors and Collaborators

• Weill Medical College of Cornell University

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 15, 2018

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03930771
• Other Study ID Numbers: 1809019558
• First Posted: Apr 29, 2019
• Last Update Posted: Aug 9, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• 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: Adenoma; Pituitary Neoplasms; Pituitary Diseases; Recurrence; Capecitabine; Temozolomide

Study Results

Participant Flow

Arm/Group Title	All Patients
Arm/Group 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). Capecitabine: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. Temozolomide: 150 to 200 mg/m2 orally on days 10 through 14.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group 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). Capecitabine: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. Temozolomide: 150 to 200 mg/m2 orally on days 10 through 14.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group 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). Capecitabine: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. Temozolomide: 150 to 200 mg/m2 orally on days 10 through 14.
Measure Participants	1
Count of Participants [Participants]	0 0%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group 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). Capecitabine: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. Temozolomide: 150 to 200 mg/m2 orally on days 10 through 14.
Measure Participants	1
Baseline	134.7
Cycle 3 Day 1	86.9
Cycle 5 Day 1	69.4
Cycle 6 Day 1	69.8
End of Treatment	80.1
Follow-Up Week 6	77.0

3. Secondary Outcome

Title	Safety, as Measured by the Number of Subjects With at Least One AE
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group 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). Capecitabine: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. Temozolomide: 150 to 200 mg/m2 orally on days 10 through 14.
Measure Participants	1
Count of Participants [Participants]	1 100%

4. Secondary Outcome

Title	Tolerability of the TMZ and Capecitabine Combination, as Measured by Number of Participants With a Dose-limiting Toxicity
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group 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). Capecitabine: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. Temozolomide: 150 to 200 mg/m2 orally on days 10 through 14.
Measure Participants	1
Count of Participants [Participants]	1 100%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data was not collected in the specified time frame for this outcome measure.

Arm/Group Title	All Patients
Arm/Group 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). Capecitabine: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. Temozolomide: 150 to 200 mg/m2 orally on days 10 through 14.
Measure Participants	0

Adverse Events

Time Frame	Adverse events were monitored from the time of consent through six months after completion of the study.
Arm/Group Title	All Patients
Arm/Group 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). Capecitabine: 1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14. Temozolomide: 150 to 200 mg/m2 orally on days 10 through 14.
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	1/1 (100%)
General disorders
Fatigue	1/1 (100%)
Musculoskeletal and connective tissue disorders
Back pain	1/1 (100%)
Nervous system disorders
Paresthesia	1/1 (100%)

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.