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A Phase II Trial of Combined Hydroxychloroquine and Sirolimus in Soft Tissue Sarcoma

Primary Purpose

Sarcoma

Status
Terminated
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
Sirolimus and hydroxychloroquine
Sponsored by
Shin Kong Wu Ho-Su Memorial Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring Sarcoma, Hydroxychloroquine, Sirolimus, PET

Eligibility Criteria

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

Inclusion Criteria:

  • Patients with Soft tissue sarcoma (including high grade or low grade soft tissue sarcoma、osteogenic sarcoma and the following 4 recurrent benign tumors which may have aggressive clinical course after initial surgical treatment : lymphangioleiomyomatosis、angiomyolipoma、giant cell tumor、phylloid tumor) that are refractory to at least first line full course of standard chemotherapy, relapsed after standard chemotherapy, or who have no standard therapy available and refused chemotherapy
  • Patients must be >/= 21 years.
  • Patients must be >/= 4 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment provided that radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks form the last dose (whichever comes first).
  • Eastern Cooperative Oncology Group(ECOG) performance status </= 2
  • Patients must have certain organ and marrow function resave defined as: White blood cell(WBC_ >/= 3,000/mL;platelets >/=100,000/mL; creatinine </= 2 X Upper Limit of Normal (ULN); total bilirubin </= 2.0; Alanine Aminotransferase(ALT;SGPT) </= 5 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 8 X ULN;cholesterol </= 350 mg/dL; triglycerides </= 400 mg/dL (sirolimus and hydroxychloroquine only).
  • Patients must be able to understand and be willing to sign a written informed consent document.

Exclusion Criteria:

  • Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
  • Pregnant or lactating women.
  • History of hypersensitivity to sirolimus.
  • History of hypersensitivity to hydroxychloroquine
  • Patients unwilling or unable to sign informed consent document.

Sites / Locations

  • Shin Kong Wu Ho-Su Memorial Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sirolimus and hydroxychloroquine

Arm Description

Both hydroxychloroquine 200 mg/tab and sirolimus 1 mg/tab are pills each are taken 2 tablet orally once daily(QD) for 2 cycles . Each treatment cycle is 28 days.

Outcomes

Primary Outcome Measures

The Maximum Standardized Uptake Values (SUVmax) Change on PET/CT Scan
A baseline whole-body [18F]-fluorodeoxyglucose(FDG) PET was performed before therapy initiation. Patients received 1 mg of Rapa and 200 mg of HCQ twice a day before a meal for 2 weeks. A second [18F]-FDG PET was performed after treatment completion. SUVs were calculated for all lesions. Regions of interest (ROI) were contoured to represent tumors (>2 cm) and organs (lungs, spleen, and liver) on all transaxial and coronal slices. ROIs were normalized for injection dose and body weight, and the maximum voxel value was recorded for each region or organ. The highest SUV measured with increased uptake was considered the SUVmax. Correlative diagnostic CT examinations were used for accurate localization of the lesions. The most intense uptake at baseline was identified as the index lesion and evaluated for treatment response.

Secondary Outcome Measures

The Toxicity
Number of Participants with Adverse Events. Toxicities parameters are according to the Nation Cancer Institute Common Terminology Criteria for Adverse Event, version 3.0.

Full Information

First Posted
December 19, 2012
Last Updated
October 5, 2015
Sponsor
Shin Kong Wu Ho-Su Memorial Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01842594
Brief Title
A Phase II Trial of Combined Hydroxychloroquine and Sirolimus in Soft Tissue Sarcoma
Official Title
A Phase II Trial of Combined Hydroxychloroquine and Sirolimus in Soft Tissue Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Why Stopped
Most patients completed only the primary objective (PET) and not went throught the secondary outcome (efficacy phase) of 8wks period.
Study Start Date
August 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shin Kong Wu Ho-Su Memorial Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Determine the objective response rate in sarcoma patients treated with hydroxychloroquine and sirolimus.
Detailed Description
This study evaluates the daily morning single dose of hydroxychloroquine /sirolimus combined therapy in sarcoma patients. Study arm were treated with hydroxychloroquine 400 mg /sirolimus 2mg gd for 8-wk therapy. Patients will be discontinued from the study after 8-wk observation period. Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study. TREATMENT PLAN: Both hydroxychloroquine 200 mg/tab and sirolimus 1 mg/tab are pills each are taken 2 tablet orally every day. Treatment will be divided into time periods called cycles. Each treatment cycle is 28 days. The exception to this 28 day cycle is when participants start taking the pills for the first time. When the hydroxychloroquine and sirolimus begins, the first cycle of 28 days begins. There are several tests and procedures that will be performed at specific time periods during protocol treatment. These include: blood work, performance status assessment, questions about medical history and medications, tumor assessment with PET/CT or MRI and, eye exams. Dose modification criteria: Participants may continue to receive study treatment as long as they experienced grade 1 or 2 side effects. The treatment drug will be 50% reduction of dose in any grade 3 toxicity; and discontinued of treatment (off-study) in any grade 4 toxicity or disease progression during treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma
Keywords
Sarcoma, Hydroxychloroquine, Sirolimus, PET

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Sirolimus and hydroxychloroquine
Arm Type
Experimental
Arm Description
Both hydroxychloroquine 200 mg/tab and sirolimus 1 mg/tab are pills each are taken 2 tablet orally once daily(QD) for 2 cycles . Each treatment cycle is 28 days.
Intervention Type
Drug
Intervention Name(s)
Sirolimus and hydroxychloroquine
Intervention Description
Both hydroxychloroquine 200 mg/tab and sirolimus 1 mg/tab are pills each are taken 2 tablet orally QD for 2 cycles . Each treatment cycle is 28 days.
Primary Outcome Measure Information:
Title
The Maximum Standardized Uptake Values (SUVmax) Change on PET/CT Scan
Description
A baseline whole-body [18F]-fluorodeoxyglucose(FDG) PET was performed before therapy initiation. Patients received 1 mg of Rapa and 200 mg of HCQ twice a day before a meal for 2 weeks. A second [18F]-FDG PET was performed after treatment completion. SUVs were calculated for all lesions. Regions of interest (ROI) were contoured to represent tumors (>2 cm) and organs (lungs, spleen, and liver) on all transaxial and coronal slices. ROIs were normalized for injection dose and body weight, and the maximum voxel value was recorded for each region or organ. The highest SUV measured with increased uptake was considered the SUVmax. Correlative diagnostic CT examinations were used for accurate localization of the lesions. The most intense uptake at baseline was identified as the index lesion and evaluated for treatment response.
Time Frame
2 Weeks
Secondary Outcome Measure Information:
Title
The Toxicity
Description
Number of Participants with Adverse Events. Toxicities parameters are according to the Nation Cancer Institute Common Terminology Criteria for Adverse Event, version 3.0.
Time Frame
2 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with Soft tissue sarcoma (including high grade or low grade soft tissue sarcoma、osteogenic sarcoma and the following 4 recurrent benign tumors which may have aggressive clinical course after initial surgical treatment : lymphangioleiomyomatosis、angiomyolipoma、giant cell tumor、phylloid tumor) that are refractory to at least first line full course of standard chemotherapy, relapsed after standard chemotherapy, or who have no standard therapy available and refused chemotherapy Patients must be >/= 21 years. Patients must be >/= 4 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment provided that radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks form the last dose (whichever comes first). Eastern Cooperative Oncology Group(ECOG) performance status </= 2 Patients must have certain organ and marrow function resave defined as: White blood cell(WBC_ >/= 3,000/mL;platelets >/=100,000/mL; creatinine </= 2 X Upper Limit of Normal (ULN); total bilirubin </= 2.0; Alanine Aminotransferase(ALT;SGPT) </= 5 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 8 X ULN;cholesterol </= 350 mg/dL; triglycerides </= 400 mg/dL (sirolimus and hydroxychloroquine only). Patients must be able to understand and be willing to sign a written informed consent document. Exclusion Criteria: Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support. Pregnant or lactating women. History of hypersensitivity to sirolimus. History of hypersensitivity to hydroxychloroquine Patients unwilling or unable to sign informed consent document.
Facility Information:
Facility Name
Shin Kong Wu Ho-Su Memorial Hospital
City
Taipei
ZIP/Postal Code
11101
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
26375670
Citation
Chi MS, Lee CY, Huang SC, Yang KL, Ko HL, Chen YK, Chung CH, Liao KW, Chi KH. Double autophagy modulators reduce 2-deoxyglucose uptake in sarcoma patients. Oncotarget. 2015 Oct 6;6(30):29808-17. doi: 10.18632/oncotarget.5060.
Results Reference
derived

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A Phase II Trial of Combined Hydroxychloroquine and Sirolimus in Soft Tissue Sarcoma

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