TMZ-Cap: Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
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 |
---|---|---|
Phase 2 |
Study Design
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
- 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
- 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.
- 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]
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
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)
More Information
Publications
None provided.- 1809019558
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
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
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%
|
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
|
Title | Safety, as Measured by the Number of Subjects With at Least One AE |
---|---|
Description | |
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%
|
Title | Tolerability of the TMZ and Capecitabine Combination, as Measured by Number of Participants With a Dose-limiting Toxicity |
---|---|
Description | |
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%
|
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. | |
---|---|---|
Adverse Event Reporting Description | ||
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
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.
Results Point of Contact
Name/Title | Rajiv Magge |
---|---|
Organization | Weill Cornell Medicine |
Phone | 212-746-6575 |
ram9116@med.cornell.edu |
- 1809019558