The Effect of Chemoradiotherapy in Patients With Refractory Pituitary Adenomas

NCT04244708 | Unknown Phase 2

• 1 other identifier: PekingUMCH-PA-TMZ
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study was to determine whether radiotherapy combined with Temozolomide is more effective than radiotherapy alone in the treatment of patients with refractory pituitary adenomas. The Basic treatment was Radiotherapy over a period of six weeks, for a total dose of 54 Gy. The150 participants were randomized to use either radiotherapy plus Temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), or radiotherapy plus placebo for 6 weeks. After a 4-week break, followed by six cycles of placebo or adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was Objective Response rate, the second end point was PFS. Greater response was anticipated in patients treated with Temozolomide+ radiotherapy than radiotherapy alone.

Conditions

Pituitary Adenomas

Keywords

Temozolomide; radiotherapy; refractory pituitary adenomas

Outcome Measures

Primary Outcomes (1)

• Tumor size

  A tumor response was defned as a decrease of more than 30% of the largest tumor diameter or stable in Tumor volume

  Four weeks after concurrent chemoradiotherapy, patients were then to receive three cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. At the end of Cycle 3 (each cycle is 28 days)

Secondary Outcomes (1)

• Hormonal responses

  Four weeks after concurrent chemoradiotherapy, patients were then to receive three cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. At the end of Cycle 3 (each cycle is 28 days)

Study Arms (2)

Radiotherapy plus temozolomide

EXPERIMENTAL

Undergoing fractionated radiotherapy at a dose of 2 Gy per fraction given once daily five days per week for a total dose of 54 Gy, plus continuous daily temozolomide (75 mg per square meter of body-surface area per day), followed by six cycles of adjuvant temozolomide.

Drug: Radiotherapy plus temozolomide

Radiotherapy plus placebo

PLACEBO COMPARATOR

Radiotherapy treatment alone undergoing fractionated radiotherapy, total 54 Gy, 2GyX27, received placebo.

Other: Radiotherapy plus placebo

Interventions

Radiotherapy plus temozolomide DRUG

undergoing fractionated radiotherapy at a dose of 2 Gy per fraction given once daily five days per week (Monday through Friday) over a period of six weeks, for a total dose of 54 Gy, plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle).

Radiotherapy plus temozolomide

Radiotherapy plus placebo OTHER

undergoing fractionated radiotherapy at a dose of 2 Gy per fraction given once daily five days per week (Monday through Friday) over a period of six weeks, for a total dose of 54 Gy, plus placebo

Radiotherapy plus placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Minimum Age: 18 Years Maximum Age: 80 Years
• Age ≥18 years, regardless of gender;
• Meet the diagnostic criteria for refractory pituitary tumors;
• The tumor showed invasive growth on imaging and rapid growth, Ki-67 labeling index ≥3%;
• The tumor recurred within a short period of time (\< 6months) after total resection;
• The tumor continues to grow after surgery and medical therapy;
• Systemic examination showed no metastases in the cranial canal or other systems throughout the body.
• Clinicopathological diagnosis of pituitary adenoma, and pathological tissue (wax or frozen tissue) can be obtained;
• Expected survival time ≥ 6 months;
• KPS score ≥70 points;
• Subjects who were able to read, understand, and sign written informed consent prior to participating in the study and were willing to comply with protocol requirements.

You may not qualify if:

• Participants cannot participate in this study if they meet any of the following conditions:
• Subjects participated in clinical studies of other drugs or medical devices within 3 months before screening.
• Known to be allergic to temozolomide capsules;
• Have been diagnosed with pituitary carcinoma or have other malignant tumors;
• Have received radiation therapy for Sella region;
• Those with severe acute and chronic diseases in various systems, whose conditions have not been effectively controlled, and whose conditions are unstable, including but not limited to:
• Patients with cardiac insufficiency (NYHA cardiac function grade ≥ 2), patients with severe heart disease such as cardiomyopathy, coronary heart disease, severe arrhythmia, etc. that are not effectively controlled;
• Severe active infections,
• Uncontrollable diabetes, hypertension / hypotension, cerebrovascular disease, gastric ulcer, respiratory disease, active autoimmune disease, etc .;
• History of any other diseases that the researcher judges to be unsuitable for the trial, etc .;
• For hepatic and renal insufficiency, hematological indicators: total bilirubin\> 1.5 × ULN, ALT, AST\> 2.5 × ULN; serum creatinine\> 2 × ULN;
• Those with a neutrophil count of less than 1.5 × 109 / L, or a platelet count of less than 100 × 109 / L, or an HGB of less than 90g / L;
• Hepatitis B surface antigen, anti-HCV, anti-HIV or syphilis antibody positive;
• Those who need to take valproic acid and drugs that can cause bone marrow depression during the application or research period;
• pregnant or lactating women or those planning to become pregnant;

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Related Publications (1)

• Burman P, Casar-Borota O, Perez-Rivas LG, Dekkers OM. Aggressive Pituitary Tumors and Pituitary Carcinomas: From Pathology to Treatment. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1585-1601. doi: 10.1210/clinem/dgad098.

  PMID: 36856733 DERIVED

MeSH Terms

Conditions

Pituitary Neoplasms

Interventions

Radiotherapy; Temozolomide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• renzhi Wang, Dr.

  pumch

  STUDY DIRECTOR

Central Study Contacts

Renzhi Wang, Dr.

CONTACT

86+18611964099; wangrz@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2019
• First Posted: January 28, 2020
• Study Start: February 10, 2020
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: January 28, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share