A Study on the Safety and Effectiveness of Temozolomide for Neoadjuvant Treatment of PPGL

Pheochromocytoma Clinical Trial

Official title:

A Study on the Safety and Effectiveness of Temozolomide for Neoadjuvant Treatment of Pheochromocytoma or Paraganglioma Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05885386
• Other study ID #: 06086-05
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2023
• Est. completion date: October 1, 2025

Study information

• Verified date: May 2023
• Source: Peking Union Medical College Hospital
• Contact: Anli Tong
• Phone: 13911413589
• Email: tonganli[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies the effectiveness oftemozolomide in the neoadjuvant therapy oflocally advanced,or unresectable pheochromocytoma or paragangliom(PPGL). Temozolomide (TMZ) is a novel oral alkylation chemotherapeutic agent. Inthisstudy,temozolomidewill be used preoperatively in order to change unresectable tumors to resectable and reduce the high risk of surgery.

Description:

The first choice for the treatment of PPGL is surgery. PPGL can be cured by complete resection of the lesion. However, some PPGLs could not be performed R0 resection due to the large tumor size and close relationship with surrounding tissues (blood vessels, kidneys, pancreas, liver, etc.). In this case, in order to achieve R0 resection, they need to undergo expand the scope of surgery, such as simultaneous resection of vital organs,and with extreamly high risks.There is no treatment option for those locally advanced or unresectable PPGLpatients currently. Temozolomide (TMZ), an oral alkylation chemotherapeutic agent, has been used in recent years and shown to have beneficial effects on metastatic PPGL with few side effects. TMZ has been recommended in National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2022 for treating metastatic PPGL patients. This prospective, single arm, phase II study is designed to evaluate the efficacy of neoadjuvant therapy with TMZ in locally advanced,or unresectable PPGL patients or patients with severe catecholamine cardiomyopathy who are intolerance of operation.TMZ was administered orally at an initial daily dose of 150 mg/m2 per day for 5 days, every 28 days preoperatively. In patients with a good tolerance during the first cycle, the dose was increased to 200 mg/m2 per day for 5 days, every 28 days. Imaging examinations will be conducted after3 courses to re-evaluate the surgical possibility and surgery risks. If the patient's tumor shrinks after 3 courses but is still unresectable, the patients will continue TMZ therapy for another 3 courses.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 1, 2025
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 70 Years

Eligibility

Inclusion Criteria:

• Provide written informed consent.
• Age 10-70 years old
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• The patient is diagnosed as pheochromocytoma or paraganglioma which is unresectable with R0 surgery, or extensive and thus maybe requiring resection of important organs, or Inoperable due to heart and other complications, or with very high surgical risk.
• Estimated life expectancy longer than 6 months.
• Confirmed non-pregnancy and lactation. During the entire study period and within 6 months after the last administration, the subjects and their spouses are willing to use efficient contraceptive measures.
• Laboratory requirements:
• Absolute granulocyte count (AGC) greater than 1.5 x 109/L;
• Platelet count greater than 80 x 109/L; 3) Hemoglobin greater than 90g/L;
• Serum bilirubin less than 1.5 x upper limit of normal (ULN);
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 x ULN; Serum creatinine less than 1.5 x ULN or creatinine clearance (CCr)=60ml/min;
• Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) = lower limit of normal value (50%).

Exclusion Criteria:

• Have other tumors.
• Patients were treated with other antitumor agents.
• Pregnant or nursing women.
• A history of allergic reactions to temozolomide or dacarbazine.
• Severe myelosuppression or abnormal coagulation.
• Severe liver and kidney insufficiency.
• Bowel obstruction or other conditions that interfere with taking medication.

Related Conditions & MeSH terms

• Paraganglioma
• Pheochromocytoma

Intervention

Drug:
• Temozolomide
TMZ was administered orally at an initial daily dose of 150 mg/m2 per day for 5 days, every 28 days preoperatively. In patients with a good tolerance during the first cycle, the dose was increased to 200 mg/m2 per day for 5 days, every 28 days.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of patients whose tumor change from unresectable to resectable tumor	The proportion of PPGL patients whose tumor change from unresectable to resectable	At the end of Cycle 3 (each cycle is 28 days)
Secondary	the objective response rate (ORR)	Defined for all patients whose tumor met the criteria of Complete Response (CR)and Partial Response (PR)	At the end of Cycle 3 (each cycle is 28 days)
Secondary	The ratio of tumor shrinkage.	The proportion of decrease in the sum of total size of the target lesions after treatment compared to before treatment.	At the end of Cycle 3 (each cycle is 28 days)
Secondary	The biochemical response.	An effective response of 24hCA, MNs meant that the concentration decreaseed by more than 40% than the baseline value or decreaseed to the normal range.	At the end of Cycle 3 (each cycle is 28 days)
Secondary	R0 resection rate	The proportion of patients with surgical resection reached R0 resection	At the end of Cycle 3 (each cycle is 28 days)
Secondary	Major pathological response rate (MPR)	Defined as the remaining surviving tumor after surgical resection do not exceed 10% of the initial tumor tissue.	At the end of Cycle 3 (each cycle is 28 days)
Secondary	Pathologic complete remission (pCR)	There is no tumor cells microscopically.	At the end of Cycle 3 (each cycle is 28 days)
Secondary	Safety of temozolomide treatment	Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events	At the end of Cycle 1 (each cycle is 28 days)