Recurrent Pituitary AdenomasPhase 2TMZ-CapNCT03930771

Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas

A Phase 2 study testing Capecitabine and Temozolomide in people with Recurrent Pituitary Adenomas, run by Weill Medical College of Cornell University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Recurrent Pituitary Adenomas
What is being tested?: Capecitabine and Temozolomide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: 1 siteUnited States
Study dates: 21 May 2019to 1 Oct 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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):

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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.

Who cannot join

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.

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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

Trial locations and contacts

1 site in 1 country.

United States1 site

Weill Cornell Medical College
New York, New York, 10065

Other trials in United States

About this study

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
Being tested: Capecitabine, Temozolomide
Medical subject headings: Pituitary Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CapecitabineDrug
1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14.
TemozolomideDrug
150 to 200 mg/m2 orally on days 10 through 14.

Study groups in NCT03930771
Study group	Role	What they receive
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). Receives: Drug: Capecitabine; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 6 months

Secondary outcomes (4)

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.
Measured: At baseline and every 8 weeks, up to 6 months
Safety, as Measured by the Number of Subjects With at Least One AE
Measured: 6 months
Tolerability of the TMZ and Capecitabine Combination, as Measured by Number of Participants With a Dose-limiting Toxicity
Measured: 6 months
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).
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 May 20191 Oct 2021

First posted29 Apr 2019
Study start21 May 2019
Primary completion19 Aug 2021
Study completion1 Oct 2021

Why it stopped: the study had a low accrual rate

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Recurrent Pituitary AdenomasStudies of the same condition, open and under way.
More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03930771
Sponsor's protocol ID: 1809019558
Acronym: TMZ-Cap
Status last verified: Jul 2022
First submitted: 25 Apr 2019
Last updated: 9 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Capecitabine and Temozolomide for Treatment of Recurrent Pituitary Adenomas
ClinicalTrials.gov ID: NCT03930771
Acronym / sponsor ID: TMZ-Cap / 1809019558
Conditions: Recurrent Pituitary Adenomas
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: the study had a low accrual rate
Enrolment: 1 participants (actual)
Lead sponsor: Weill Medical College of Cornell UniversityUniversity, hospital or other
Study start: 21 May 2019 (actual)
Primary completion: 19 Aug 2021 (actual)
Study completion: 1 Oct 2021 (actual)
First posted: 29 Apr 2019 (actual)
Results: Posted 9 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
All Patients	Experimental	Drug: Capecitabine, Drug: TemozolomideAll 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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

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.

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Capecitabine1500mg/m2 orally per day (divided into two doses with maximum daily dose of 2500mg) on days 1 through 14.	Drug	All Patients
Temozolomide150 to 200 mg/m2 orally on days 10 through 14.	Drug	All Patients

Primary outcome

Number of Subjects With Radiographic Response, as Defined by the RECIST Criteria.
Time frame: 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.

4 secondary outcomes

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
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

Results and safety

Results posted to the registry on 9 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Patients	1	1

Primary outcome: Number of Subjects With Radiographic Response, as Defined by the RECIST Criteria.

Time frame: 6 months. Count of participants. Unit: Participants

Measure	All Patients n = 1
Value	0

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were monitored from the time of consent through six months after completion of the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Patients	0 of 1 (0%)	1 of 1 (100%)	0 of 1

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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rajiv Magge, MD principal investigator

Weill Medical College of Cornell University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Capecitabine and Temozolomide in people with Recurrent Pituitary Adenomas, run by Weill Medical College of Cornell University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Radiographic Response, as Defined by the RECIST Criteria. (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03930771.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2022.