- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01281865
Everolimus in Combination With Imatinib Mesylate in Treating Patients With Locally Advanced, Locally Recurrent, or Metastatic Soft Tissue Sarcoma
A Phase 1b/2 Study of Imatinib in Combination With Everolimus in Synovial Sarcoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose (MTD) of everolimus in combination with imatinib mesylate in patients with synovial sarcoma. (Phase I) II. To determine the overall response rate (RR = CR + PR). (Phase II)
SECONDARY OBJECTIVES:
I. To determine RR, progression-free survival (PFS), and overall survival (OS). (Phase I) II. To determine predictors of response. (Phase II) III. To obtain tissue biopsy and plasma samples for correlative studies pre- and post-treatment. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of everolimus followed by a phase II study.
Patients receive everolimus orally (PO) once daily and imatinib mesylate PO once daily on days 1-28. Course repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood and tumor tissue sample collection at baseline and periodically during study for correlative biomarker and protein expression studies.
After completion of study therapy, patients are followed up for 30 days.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically confirmed synovial sarcoma that is platelet-derived growth factor receptor, alpha polypeptide positive (PDGFRA+)
- Metastatic and/or locally advanced or locally recurrent disease
Patients must consent to tumor biopsies before therapy and after the second week of therapy
- Patients who do not have accessible tumor for biopsy may be enrolled at the discretion of the principal investigator
Patients must have measurable disease, by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
- Tumor lesions that are situated in a previously irradiated area may be considered measurable for the purposes of this study only if there is evidence of growth of the area following a course of irradiation that cannot be attributed to necrosis or bleeding into the tumor
- Patients with brain metastasis that has been treated with definitive surgery or radiotherapy, and who have been clinically stable for 3 months following the procedure with no neurological signs or symptoms and no requirement for systemic glucocorticoids, are eligible for study
- ECOG performance status 0-1
- Life expectancy greater than 3 months
- ANC ≥ 1,500/mm³
- Platelet count ≥ 75,000/mm³
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (except for patients with known Gilbert syndrome)
- AST/ALT ≤ 3 times ULN
- Serum creatinine ≤ 1.5 times ULN
- Serum glucose ≤ 120 mg/dL
- Total cholesterol < 300 mg/dL
- Triglycerides < 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) during therapy and for at least 8 weeks after completion of therapy
- Patients must not have current evidence of another malignancy
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus, imatinib mesylate, or other agents used in the study
- No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, including HIV, active hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled diabetes, or psychiatric illness/social situations that would limit compliance with study requirements
- No patients with significant compromised respiratory problems or an active and unexplained pneumonitis
- No concurrent combination antiretroviral therapy for HIV-positive patients
At least 4 weeks since any number of prior chemotherapy regimens (6 weeks for carmustine or mitomycin C) for recurrent/metastatic disease
- No prior tyrosine kinase inhibitors
- Recovered to ≤ grade 1 NCI CTCAE version 4 adverse events related to prior tumor-specific therapy
No patients who have had major surgery within the past 4 weeks, or who have not recovered from adverse events to ≤ grade 1 NCI CTCAE adverse events associated with surgery
- Surgical changes not expected to improve ( e.g., removal of muscle tissue) allowed
- No prior mTOR inhibitors, such as sirolimus, everolimus, ridaforolimus, or temsirolimus
- No other concurrent investigational agents
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (everolimus and imatinib mesylate)
Patients receive everolimus PO once daily and imatinib mesylate PO once daily on days 1-28.
Course repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and tumor tissue sample collection at baseline and periodically during study for correlative biomarker and protein expression studies.
|
Given PO
Other Names:
Correlative studies
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Response Rate (CR + PR) Assessed by RECIST 1.1 (Phase II)
Time Frame: At 8 weeks
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At 8 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mary Louise Keohan, Memorial Sloan Kettering Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Connective Tissue
- Sarcoma
- Sarcoma, Synovial
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Imatinib Mesylate
- Everolimus
Other Study ID Numbers
- NCI-2011-02577 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U01CA069856 (U.S. NIH Grant/Contract)
- P30CA008748 (U.S. NIH Grant/Contract)
- CDR0000693826
- 10-167 (Other Identifier: Memorial Sloan-Kettering Cancer Center)
- 8603 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Adult Soft Tissue Sarcoma
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Radiation Therapy Oncology GroupNational Cancer Institute (NCI)WithdrawnRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue SarcomaUnited States, Canada
-
National Institutes of Health Clinical Center (CC)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue Sarcoma | Stage IVB Adult Soft Tissue Sarcoma
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma | Stage II Adult Soft Tissue SarcomaUnited States
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National Cancer Institute (NCI)TerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
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Northwestern UniversityAVEO Pharmaceuticals, Inc.CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
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National Cancer Institute (NCI)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
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National Cancer Institute (NCI)Radiation Therapy Oncology GroupTerminatedRecurrent Adult Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma AJCC v7 | Stage II Adult Soft Tissue Sarcoma AJCC v7 | Stage III Adult Soft Tissue Sarcoma AJCC v7United States
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National Cancer Institute (NCI)National Comprehensive Cancer NetworkCompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
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City of Hope Medical CenterTerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Adult LiposarcomaUnited States
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