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

NCT01842594 | Terminated Phase 2 Results DMC

• 1 other identifier: 20120306M
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Determine the objective response rate in sarcoma patients treated with hydroxychloroquine and sirolimus.

Conditions

Sarcoma

Keywords

Sarcoma, Hydroxychloroquine, Sirolimus, PET

Outcome Measures

Primary Outcomes (1)

• 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.

  2 Weeks

Secondary Outcomes (1)

• The Toxicity

  2 Weeks

Study Arms (1)

Sirolimus and hydroxychloroquine

EXPERIMENTAL

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

Interventions

Sirolimus and hydroxychloroquine DRUG

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.

Sirolimus and hydroxychloroquine

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shin Kong Wu Ho-Su Memorial Hospital: lead

Study Sites (1)

Shin Kong Wu Ho-Su Memorial Hospital

Taipei, Taiwan, 11101, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 26375670 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

Sirolimus; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Kwan-Hwa Chi
• Organization: Shin Kong Wu Ho-Su Memorial Hospital

M006565@ms.skh.org.tw

+886-28332211

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: April 29, 2013
• Study Start: August 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: November 3, 2015
• Results First Posted: November 3, 2015

Record last verified: 2015-10

Locations

TW (1)