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

This study has been terminated.
(Most patients completed only the primary objective (PET) and not went throught the secondary outcome (efficacy phase) of 8wks period.)
Information provided by (Responsible Party):
Shin Kong Wu Ho-Su Memorial Hospital
ClinicalTrials.gov Identifier:
First received: December 19, 2012
Last updated: October 5, 2015
Last verified: October 2015
Determine the objective response rate in sarcoma patients treated with hydroxychloroquine and sirolimus.

Condition Intervention Phase
Drug: Sirolimus and hydroxychloroquine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Combined Hydroxychloroquine and Sirolimus in Soft Tissue Sarcoma

Resource links provided by NLM:

Further study details as provided by Shin Kong Wu Ho-Su Memorial Hospital:

Primary Outcome Measures:
  • The Maximum Standardized Uptake Values (SUVmax) Change on PET/CT Scan [ Time Frame: 2 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 Weeks ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events. Toxicities parameters are according to the Nation Cancer Institute Common Terminology Criteria for Adverse Event, version 3.0.

Enrollment: 13
Study Start Date: August 2012
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sirolimus and hydroxychloroquine
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.
Drug: Sirolimus and hydroxychloroquine

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.

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.


  1. 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.
  2. 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.
  3. 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.


Ages Eligible for Study:   21 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01842594

Shin Kong Wu Ho-Su Memorial Hospital
Taipei, Taiwan, 11101
Sponsors and Collaborators
Shin Kong Wu Ho-Su Memorial Hospital
  More Information

No publications provided

Responsible Party: Shin Kong Wu Ho-Su Memorial Hospital
ClinicalTrials.gov Identifier: NCT01842594     History of Changes
Other Study ID Numbers: 20120306M
Study First Received: December 19, 2012
Results First Received: June 8, 2015
Last Updated: October 5, 2015
Health Authority: Taiwan: Department of Health

Keywords provided by Shin Kong Wu Ho-Su Memorial Hospital:
Sarcoma, Hydroxychloroquine, Sirolimus, PET

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2015