Clinical trial NCT04244708: The Effect of Chemoradiotherapy in Patients With Refractory Pituitary Adenomas
Official title: Radiotherapy Plus Concomitant Temozolomide for Refractory Pituitary Adenomas，A Randomized，Double-blind, Placebo-controlled Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Pituitary Adenomas
Keywords: Temozolomide; radiotherapy; refractory pituitary adenomas
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2020-01-28
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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, which is consisted of fractionated focal irradiation 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. 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, patients were then to receive up to six cycles of adjuvant temozolomide or placebo according to the standard 5-day schedule every 28 days. The dose was 150 mg per square meter for the first cycle and was increased to 200 mg per square meter beginning with the second cycle, so long as there were no hematologic toxic effects 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.

Eligibility criteria: Inclusion Criteria:

Minimum Age: 18 Years Maximum Age: 80 Years

1. Age ≥18 years, regardless of gender;
2. Meet the diagnostic criteria for refractory pituitary tumors;

   1. The tumor showed invasive growth on imaging and rapid growth, Ki-67 labeling index ≥3%;
   2. The tumor recurred within a short period of time (\< 6months) after total resection;
   3. The tumor continues to grow after surgery and medical therapy;
   4. Systemic examination showed no metastases in the cranial canal or other systems throughout the body.
3. Clinicopathological diagnosis of pituitary adenoma, and pathological tissue (wax or frozen tissue) can be obtained;
4. Expected survival time ≥ 6 months;
5. KPS score ≥70 points;
6. 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.

Exclusion Criteria:

Participants cannot participate in this study if they meet any of the following conditions:

1. Subjects participated in clinical studies of other drugs or medical devices within 3 months before screening.
2. Known to be allergic to temozolomide capsules;
3. Have been diagnosed with pituitary carcinoma or have other malignant tumors;
4. Have received radiation therapy for Sella region;
5. 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:

   1. 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;
   2. Severe active infections,
   3. Uncontrollable diabetes, hypertension / hypotension, cerebrovascular disease, gastric ulcer, respiratory disease, active autoimmune disease, etc .;
   4. History of any other diseases that the researcher judges to be unsuitable for the trial, etc .;
6. For hepatic and renal insufficiency, hematological indicators: total bilirubin\> 1.5 × ULN, ALT, AST\> 2.5 × ULN; serum creatinine\> 2 × ULN;
7. 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;
8. Hepatitis B surface antigen, anti-HCV, anti-HIV or syphilis antibody positive;
9. Those who need to take valproic acid and drugs that can cause bone marrow depression during the application or research period;
10. pregnant or lactating women or those planning to become pregnant;
11. People with history of difficulty in drawing blood;
12. People with a history of bleeding disorders;
13. Subjects had a history of drug use or smoking and alcohol abuse within 6 months before enrollment;
14. Researchers do not consider it appropriate to participate in the trial.

Primary outcomes:
measure: Tumor size
timeFrame: 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:
measure: Hormonal responses
timeFrame: 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)
Other outcomes:
Locations:
Study officials:
affiliation: pumch
name: renzhi Wang, Dr.
role: STUDY_DIRECTOR
References: