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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
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.
Peking Union Medical College Hospital
Beijing, China
RECRUITINGThe proportion of patients whose tumor change from unresectable to resectable tumor
The proportion of PPGL patients whose tumor change from unresectable to resectable
Time frame: At the end of Cycle 3 (each cycle is 28 days)
the objective response rate (ORR)
Defined for all patients whose tumor met the criteria of Complete Response (CR)and Partial Response (PR)
Time frame: At the end of Cycle 3 (each cycle is 28 days)
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.
Time frame: At the end of Cycle 3 (each cycle is 28 days)
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.
Time frame: At the end of Cycle 3 (each cycle is 28 days)
R0 resection rate
The proportion of patients with surgical resection reached R0 resection
Time frame: At the end of Cycle 3 (each cycle is 28 days)
Major pathological response rate (MPR)
Defined as the remaining surviving tumor after surgical resection do not exceed 10% of the initial tumor tissue.
Time frame: At the end of Cycle 3 (each cycle is 28 days)
Pathologic complete remission (pCR)
There is no tumor cells microscopically.
Time frame: At the end of Cycle 3 (each cycle is 28 days)
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Safety of temozolomide treatment
Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events
Time frame: At the end of Cycle 1 (each cycle is 28 days)