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

Primary Purpose

Pheochromocytoma, Paraganglioma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Anlotinib hydrochloride
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pheochromocytoma focused on measuring Pheochromocytoma or Paraganglioma, Neoadjuvant Treatment, Anlotinib

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Provide written informed consent. 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 with very high surgical risk. Laboratory requirements: Absolute granulocyte count (AGC) greater than 1.5 x 109/L; Platelet count greater than 80 x 109/L; 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%). 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. Exclusion Criteria: Patients who have previously used other anti-vascular targeted drugs, such as sunitinib, bevacizumab, endurance, etc. Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery within 4 weeks prior to kinase inhibitor therapy. Patients with another primary malignancy within 5 years prior to starting study drug. Those who have multiple factors that affect oral medications (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.). Active or uncontrolled intercurrent illness including, but not limited to: Patients with unsatisfactory blood pressure control (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg); Patients with uncontrolled myocardial ischemia or myocardial infarction, arrhythmia (including QTC≥480ms), and uncontrolled congestive heart failure,grade ≥2(New York Heart Association ); Ongoing or active infection; Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral treatment; Renal failure requires hemodialysis or peritoneal dialysis; Have a history of immunodeficiency, including HIV or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; Diabetes is poorly controlled (fasting blood glucose (FBG)> 10mmol/L); Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein content is confirmed to be greater than 1.0 g; Patients who have seizures and need treatment; Any of the following conditions ≤ 6 months prior to registration: Cerebrovascular accident (CVA) or transient ischemic attack (TIA); Serious or unstable cardiac arrhythmia; Pulmonary embolism, untreated deep venous thrombosis (DVT). Those who have a history of psychotropic drug abuse and cannot be quit or have mental disorders. Imaging shows that the tumor has invaded important blood vessels or the investigator judges that the tumor is very likely to invade important blood vessels and cause fatal bleeding during the follow-up study. Regardless of the severity, patients with any signs of bleeding or medical history; within 4 weeks before enrollment, patients with any bleeding or bleeding event ≥ CTCAE grade 3, unhealed wounds, ulcers or fractures. Participated in other clinical trials within 4 weeks. Patients are using drugs that interact with anlotinib. Any of the following: Pregnant women, Nursing women, Men or women of childbearing potential who are unwilling to employ adequate contraception. Patients with stable disease, and no desire for surgery.

Sites / Locations

  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Anlotinib hydrochloride

Arm Description

Patients receive anlotinib hydrochloride 8-12mg orally once daily on days 1-14. Courses repeat every 21 days

Outcomes

Primary Outcome Measures

The proportion of PPGL patients whose tumor change from unresectable to resectable tumor.
The proportion of PPGL patients whose tumor change from unresectable to resectable

Secondary Outcome Measures

The objective response rate (ORR)
Determined by the RECIST 1.1 criteria
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.
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.
R0 resection rate.
The proportion of patients with surgical resection reached R0 resection
Major pathological response rate (MPR).
Defined as the remaining surviving tumor after surgical resection do not exceed 10% of the initial tumor tissue.
Pathologic complete remission (pCR).
There is no tumor cells microscopically.
Safety of anlotinib treatment.
Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events.

Full Information

First Posted
April 10, 2023
Last Updated
May 22, 2023
Sponsor
Peking Union Medical College Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05883085
Brief Title
A Study on the Safety and Effectiveness of Anlotinib for Neoadjuvant Treatment of PPGL
Official Title
A Study on the Safety and Effectiveness of Anlotinib for Neoadjuvant Treatment of Locally Advanced, or Unresectable Pheochromocytoma or Paraganglioma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2022 (Actual)
Primary Completion Date
December 1, 2023 (Anticipated)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This phase II trial studies the effectiveness of anlotinib hydrochloride in the neoadjuvant therapy of locally advanced, or unresectable pheochromocytoma or paragangliom(PPGL). Anrotinib is used preoperatively in order to change unresectable tumors to resectable and reduce the high risk of surgery.
Detailed Description
This prospective, single arm phase II study is designed to evaluate the efficacy of neoadjuvant therapy with anlotinib hydrochloride in locally advanced,or unresectable PPGL patients. Locally advanced,or unresectable PPGL patients receive anlotinib hydrochloride(10-12mg orally once daily on days 1-14, courses repeat every 21 days). Imaging examinations will be conducted after 4 courses to re-evaluate the surgical possibility. If the patient's tumor shrinks after 4 courses but is still unresectable, the patients will continue antirotinib therapy for another 4 courses. PRIMARY OBJECTIVES: The proportion of patients whose PPGL change from unresectable to resectable tumor. SECONDARY OBJECTIVES: To determine the objective response rate (ORR) . To determine the ratio of tumor shrinkage. To determine the biochemical response . To determine the R0 resection rate. To determine the Major pathological response rate (MPR). To determine the pathologic complete remission(pCR). To assess the safety of anlotinib treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pheochromocytoma, Paraganglioma
Keywords
Pheochromocytoma or Paraganglioma, Neoadjuvant Treatment, Anlotinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Anlotinib hydrochloride
Arm Type
Other
Arm Description
Patients receive anlotinib hydrochloride 8-12mg orally once daily on days 1-14. Courses repeat every 21 days
Intervention Type
Drug
Intervention Name(s)
Anlotinib hydrochloride
Other Intervention Name(s)
Anlotinib
Intervention Description
Patients receive anlotinib hydrochloride 8-12mg orally once daily on days 1-14. Courses repeat every 21 days
Primary Outcome Measure Information:
Title
The proportion of PPGL patients whose tumor change from unresectable to resectable tumor.
Description
The proportion of PPGL patients whose tumor change from unresectable to resectable
Time Frame
At the end of Cycle 4 (each cycle is 21 days)
Secondary Outcome Measure Information:
Title
The objective response rate (ORR)
Description
Determined by the RECIST 1.1 criteria
Time Frame
At the end of Cycle 4 (each cycle is 21 days)
Title
The ratio of tumor shrinkage
Description
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 4 (each cycle is 21 days)
Title
The biochemical response.
Description
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 4 (each cycle is 21 days)
Title
R0 resection rate.
Description
The proportion of patients with surgical resection reached R0 resection
Time Frame
At the end of Cycle 4 (each cycle is 21 days)
Title
Major pathological response rate (MPR).
Description
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 4 (each cycle is 21 days)
Title
Pathologic complete remission (pCR).
Description
There is no tumor cells microscopically.
Time Frame
At the end of Cycle 4 (each cycle is 21 days)
Title
Safety of anlotinib treatment.
Description
Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events.
Time Frame
At the end of Cycle 1 (each cycle is 21 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provide written informed consent. 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 with very high surgical risk. Laboratory requirements: Absolute granulocyte count (AGC) greater than 1.5 x 109/L; Platelet count greater than 80 x 109/L; 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%). 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. Exclusion Criteria: Patients who have previously used other anti-vascular targeted drugs, such as sunitinib, bevacizumab, endurance, etc. Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery within 4 weeks prior to kinase inhibitor therapy. Patients with another primary malignancy within 5 years prior to starting study drug. Those who have multiple factors that affect oral medications (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.). Active or uncontrolled intercurrent illness including, but not limited to: Patients with unsatisfactory blood pressure control (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg); Patients with uncontrolled myocardial ischemia or myocardial infarction, arrhythmia (including QTC≥480ms), and uncontrolled congestive heart failure,grade ≥2(New York Heart Association ); Ongoing or active infection; Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral treatment; Renal failure requires hemodialysis or peritoneal dialysis; Have a history of immunodeficiency, including HIV or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; Diabetes is poorly controlled (fasting blood glucose (FBG)> 10mmol/L); Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein content is confirmed to be greater than 1.0 g; Patients who have seizures and need treatment; Any of the following conditions ≤ 6 months prior to registration: Cerebrovascular accident (CVA) or transient ischemic attack (TIA); Serious or unstable cardiac arrhythmia; Pulmonary embolism, untreated deep venous thrombosis (DVT). Those who have a history of psychotropic drug abuse and cannot be quit or have mental disorders. Imaging shows that the tumor has invaded important blood vessels or the investigator judges that the tumor is very likely to invade important blood vessels and cause fatal bleeding during the follow-up study. Regardless of the severity, patients with any signs of bleeding or medical history; within 4 weeks before enrollment, patients with any bleeding or bleeding event ≥ CTCAE grade 3, unhealed wounds, ulcers or fractures. Participated in other clinical trials within 4 weeks. Patients are using drugs that interact with anlotinib. Any of the following: Pregnant women, Nursing women, Men or women of childbearing potential who are unwilling to employ adequate contraception. Patients with stable disease, and no desire for surgery.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anli Tong
Phone
13911413589
Email
tonganli@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yunying Cui
Phone
18365609818
Email
cuiyunying@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anli Tong
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anli Tong
Phone
13911413589
Email
tonganli@hotmail.com

12. IPD Sharing Statement

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

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