Everolimus in Combination With Imatinib Mesylate in Treating Patients With Locally Advanced, Locally Recurrent, or Metastatic Soft Tissue Sarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01281865
First received: January 21, 2011
Last updated: April 1, 2014
Last verified: June 2013
  Purpose

This phase I/II clinical trial is studying the side effects and best dose of everolimus when given with imatinib mesylate and to see how well they work in treating patients with locally advanced, locally recurrent or metastatic soft tissue sarcoma. Everolimus and imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Adult Synovial Sarcoma
Recurrent Adult Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Other: diagnostic laboratory biomarker analysis
Drug: everolimus
Drug: imatinib mesylate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of Imatinib in Combination With Everolimus in Synovial Sarcoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) of everolimus in combination with imatinib mesylate determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (Phase I) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    DLT is defined as the occurrence of any unexpected Grade 3 non-hematologic toxicity including diarrhea (despite use of antidiarrheal prophylaxis or glucocorticoids), or nausea and vomiting (despite use of maximal anti-emetics), and any Grade 4 toxicity.

  • Response rate (CR + PR) assessed by RECIST 1.1 (Phase II) [ Time Frame: At 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier method.

  • Overall survival (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier method.


Enrollment: 14
Study Start Date: January 2011
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other: diagnostic laboratory biomarker analysis
Correlative studies
Drug: everolimus
Given PO
Other Names:
  • 42-O-(2-hydroxy)ethyl rapamycin
  • Afinitor
  • RAD001
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01281865

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Mary Louise Keohan Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01281865     History of Changes
Other Study ID Numbers: NCI-2011-02577, NCI-2011-02577, CDR0000693826, 10-167, 8603, P30CA008748, U01CA069856
Study First Received: January 21, 2011
Last Updated: April 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Synovial
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Everolimus
Sirolimus
Imatinib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 02, 2014