Clinical trial NCT05885386: A Study on the Safety and Effectiveness of Temozolomide for Neoadjuvant Treatment of PPGL
Official title: A Study on the Safety and Effectiveness of Temozolomide for Neoadjuvant Treatment of Pheochromocytoma or Paraganglioma Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pheochromocytoma
Paraganglioma
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-06-01
Enrollment: 20
Sex: ALL
Minimum age (years): 10
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.)
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of patients whose tumor change from unresectable to resectable tumor
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
Secondary outcomes:
measure: the objective response rate (ORR)
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
measure: The ratio of tumor shrinkage.
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
measure: The biochemical response.
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
measure: R0 resection rate
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
measure: Major pathological response rate (MPR)
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
measure: Pathologic complete remission (pCR)
timeFrame: At the end of Cycle 3 (each cycle is 28 days)
measure: Safety of temozolomide treatment
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
Study officials:
affiliation: Peking Union Medical College Hospital
name: Anli Tong
role: PRINCIPAL_INVESTIGATOR
References: