Clinical trial NCT05858177: The Efficacy and Safety of Temozolomide in Patients With MPPGL
Official title: The Efficacy and Safety of Temozolomide in Patients With Metastatic Pheochromocytoma or Paraganglioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pheochromocytoma, Metastatic
Paraganglioma, Malignant
Pheochromocytoma Malignant
Keywords: Pheochromocytoma or Paraganglioma
metastasis
Temozolomide
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-05-15
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Metastatic pheochromocytoma / paraganglioma (MPP) are rare while the prognosis was poor. Temozolomide (TMZ) is a novel oral alkylation chemotherapeutic agent. TMZ has been recommended in National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2019 for treating MPP patients.However, studies investigating TMZ efficacy in MPP patients are extremely limited. The largest study involved only 15 patients till date. The safety and efficacy of TMZ treatment in MPP patients need to be verified in larger studies.

Detailed description: Patients with histologically or radiologically confirmed MPP were enrolled. TMZ was administered orally at an initial daily dose of 150 mg/m2 per day for 5 days, every 28 days. 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. Plasma normetanephrine and metanephrine (MNs), 24-hour urinary catecholamine excretion (24hCA) and neuron specific enolase (NSE) were measured at baseline and every 1-3 cycle. Contrast-enhanced computed tomography（CT ）of chest, abdomen and pelvis were used to assess measurable target lesions at baseline and every 3 cycles. For patients who only had bone metastases or no measurable target lesions, TMZ efficacy was evaluated by 18F-fluorodeoxyglucose (18F-FDG-PET/CT). The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors（RECIST) 1.1/PERCIST1.0. Secondary endpoints included biochemical (catecholamine levels) response rate (BRR), progression-free survival (PFS) and safety. The investigators will try to explore which patients are more suitable for TMZ treatment.

Eligibility criteria: Inclusion Criteria:

Patients with metastatic pheochromocytomas and paragangliomas. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

Estimated life expectancy longer than 6 months. Having normal organ function as defined by hemoglobin levels ≥10 g/dL, absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 80 x 109/L, total bilirubin ≤1.5 institutional upper limit, aspartate aminotransferase ≤5 institutional upper limit, alanine aminotransferase ≤5 institutional upper limit, and serum creatinine \<3.0 mg/dL.

Exclusion Criteria:

Didn't meet eligibility for organ function. Pregnancy or breastfeeding. Uncontrolled congestive heart failure and severe infection.

Primary outcomes:
measure: disease control rate (DCR)
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
measure: objective response rate (ORR)
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
Secondary outcomes:
measure: progression-free survival (PFS)
timeFrame: At least 1 cycle(each cycle is 28 days), up to 100 weeks,From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: biochemical response
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Incidence of adverse events
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Anli Tong
role: PRINCIPAL_INVESTIGATOR
References: