Temozolomide in Aggressive Pituitary Neuroendocrine Tumors: A Latin American Multicenter Retrospective Cohort (TMZ-LATAM) (TEMPLA)

TEMPLA: TEMozolomide in Pituitary Tumors - Latin America - A Multicenter Retrospective Cohort of Temozolomide Therapy in Aggressive Pituitary Neuroendocrine Tumors and Pituitary Carcinomas

Temozolomide is the main chemotherapy drug used for aggressive pituitary tumors and pituitary carcinomas that do not respond to standard treatments like surgery or radiation. Most of what is known about how well this treatment works comes from small studies in Europe and the United States, with very little data from Latin America. Building on a previous multicenter study conducted in Brazil, this study (TEMPLA) expands data collection to additional centers across Latin America to better understand how patients in this region respond to temozolomide, how long the treatment controls the tumor, and whether certain tumor characteristics (such as MGMT status) can help predict which patients are more likely to benefit.

Study Overview

• Status: Not yet recruiting
• Conditions: Pituitary Neoplasms
• Intervention / Treatment: Drug: temozolamide; Drug: Temozolamide

Detailed Description

Temozolomide is the first-line chemotherapeutic agent recommended for aggressive pituitary neuroendocrine tumors (PitNETs) and pituitary carcinomas refractory to standard therapy, including surgery and radiotherapy. Current evidence supporting its use derives largely from small case series and single-country cohorts, with limited data representative of Latin American populations.

TEMPLA (TEMozolomide in Pituitary tumors - Latin America) is a retrospective, multicenter cohort study that expands a previously conducted national Brazilian cohort on temozolomide use in aggressive PitNETs and pituitary carcinomas to a broader Latin American regional scope. Participating centers will retrospectively identify patients treated with temozolomide for histologically confirmed aggressive PitNET (defined by Knosp grade ≥3, radiological growth >20% within 6 months, and/or progression despite optimized standard therapy) or histologically/clinically confirmed pituitary carcinoma.

Data will be collected via a standardized electronic case report form (REDCap), with harmonized diagnostic and response criteria applied across all participating sites to minimize inter-center heterogeneity. Mandatory variables include tumor subtype and lineage, temozolomide dose and treatment duration, and radiological response assessed from pre- and post-treatment imaging. MGMT status (by immunohistochemistry and/or promoter methylation analysis, where locally available) will be collected as a secondary variable and analyzed as an exploratory predictor of treatment response.

The primary aim of this study is to characterize the radiological response rate to temozolomide across Latin American centers. Secondary aims include estimating progression-free survival and overall survival following temozolomide initiation, evaluating the association between MGMT status and treatment response, and describing treatment-related adverse events.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: RAFAEL Loch BATISTA, MD PhD; Phone Number: +5511992052473; Email: rafael.loch@hc.fm.usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients diagnosed with aggressive pituitary neuroendocrine tumors (PitNETs) or pituitary carcinomas who were treated with temozolomide as part of routine clinical management at participating centers across Latin America, including a previously established Brazilian multicenter cohort. Patients were identified retrospectively through review of institutional pathology, oncology, and endocrinology records. The population reflects real-world clinical practice, encompassing diverse tumor subtypes (functioning and non-functioning PitNETs) and variable temozolomide dosing protocols, rather than a population selected under a standardized experimental treatment regimen.

Description

Inclusion Criteria:

Histologically confirmed pituitary neuroendocrine tumor (PitNET) meeting criteria for aggressive behavior (Knosp grade ≥3, radiological tumor growth >20% within 6 months, and/or progression despite optimized standard therapy including surgery and/or radiotherapy), OR histologically or clinically confirmed pituitary carcinoma (defined by the presence of craniospinal or systemic metastasis) Treatment with temozolomide, at any dose or duration, administered for the above indication Availability of pre-treatment and post-treatment imaging sufficient to assess radiological response Temozolomide treatment initiated within the defined study period

Exclusion Criteria:

Insufficient clinical or imaging data to assess the primary outcome measure Temozolomide administered for an indication other than aggressive PitNET or pituitary carcinoma Loss to follow-up before any post-treatment imaging assessment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Temozolomide-Treated Patients; Patients with histologically confirmed aggressive pituitary neuroendocrine tumor (PitNET) or pituitary carcinoma who received temozolomide chemotherapy as part of clinical management, following disease progression despite standard therapy (surgery and/or radiotherapy). Data on temozolomide dose, treatment duration, and radiological response were retrospectively collected from participating Latin American centers. No intervention was assigned as part of this study; temozolomide was administered as standard clinical care prior to data collection.

Drug: temozolamide; Temozolomide, an oral alkylating chemotherapeutic agent, administered as part of routine clinical management for aggressive pituitary neuroendocrine tumors (PitNETs) and pituitary carcinomas refractory to standard therapy. Dosing regimens, cycle duration, and total number of cycles varied according to each treating center's clinical protocol and were not standardized as part of this study. Temozolomide was not assigned by the investigators for research purposes; all treatment decisions were made independently by the treating clinical team prior to data collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological Response Rate to Temozolomide		From initiation of temozolomide treatment to best radiological response observed, assessed up to 5 years
Radiological response	Radiological response to temozolomide will be classified as complete response, partial response, stable disease, or progressive disease, based on comparison of pre-treatment and post-treatment imaging (MRI) available for each patient. Response classification will follow criteria adapted from RECIST where applicable, acknowledging that formal RECIST assessment may not have been systematically applied at the time of clinical treatment in all participating centers.	From initiation of temozolomide treatment to radiological or clinical disease progression, or death from any cause, whichever occurs first, assessed up to 5 years

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 10, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 4, 2026
• First Submitted That Met QC Criteria: July 4, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 4, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Temozolomide; Aggressive Pituitary Tumor; Pituitary Carcinoma; PitNET; MGMT; Latin America; Retrospective Cohort; Multicenter Study
• Additional Relevant MeSH Terms: Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Pituitary Diseases; Pituitary Neoplasms
• Other Study ID Numbers: TMZ-LATAM-2026-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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