Ixabepilone and Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01375829
Recruitment Status : Active, not recruiting
First Posted : June 17, 2011
Last Update Posted : March 5, 2018
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase I trial studies the side effects and best dose of ixabepilone and temsirolimus in treating patients with solid tumors that have spread from the primary site to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ixabepilone together with temsirolimus may kill more tumor cells.

Condition or disease Intervention/treatment Phase
Adult Solid Neoplasm Drug: Ixabepilone Other: Pharmacological Study Drug: Temsirolimus Phase 1

Detailed Description:


I. To determine the maximally tolerated dose (MTD) of the combination of ixabepilone and temsirolimus in patients with advanced solid tumors.

II. To describe toxicity profiles associated with the combination of ixabepilone and temsirolimus.

III. To assess preliminary efficacy of the combination of ixabepilone and temsirolimus.

OUTLINE: This is a dose-escalation study.

Patients receive ixabepilone intravenously (IV) over 3 hours on day 1 and temsirolimus IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 months.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Ixabepilone and Temsirolimus in Adult Patients With Advanced Solid Tumors
Actual Study Start Date : June 27, 2011
Actual Primary Completion Date : February 3, 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment (ixabepilone, temsirolimus)
Patients receive ixabepilone IV over 3 hours on day 1 and temsirolimus IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Ixabepilone
Given IV
Other Names:
  • (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione
  • Azaepothilone B
  • BMS 247550
  • BMS-247550
  • BMS247550
  • Epothilone
  • Epothilone-B BMS 247550
  • Ixempra

Other: Pharmacological Study
Correlative studies

Drug: Temsirolimus
Given IV
Other Names:
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
  • Torisel

Primary Outcome Measures :
  1. MTD of the combination of ixabepilone and temsirolimus, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) [ Time Frame: 21 days ]

Secondary Outcome Measures :
  1. Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 months ]
    The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

  2. Incidence of overall toxicity graded according to Common Toxicity Criteria standard grading [ Time Frame: Up to 3 months ]
    Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  3. Best response, defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence [ Time Frame: Up to 3 months ]
    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).

  4. Time until any treatment related toxicity [ Time Frame: Up to 3 months ]
  5. Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 months ]
  6. Time until hematologic nadirs (white blood cells, absolute neutrophil count, platelets) [ Time Frame: Up to 3 months ]
  7. Time to progression [ Time Frame: Up to 3 months ]
  8. Time to treatment failure [ Time Frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult patients with histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative measures or other therapy that provide survival benefit do not exist or are no longer effective
  • Patients may not have had more than two systemic therapeutic regimens in the metastatic disease setting with the following exceptions: hormonal therapy (e.g. tamoxifen, aromatase inhibitors, anti-androgen therapy, etc.)
  • Patients with non-measurable, but assessable, disease will be allowed
  • Absolute neutrophil count >= 1500/mcL
  • Hemoglobin >= 9.0 g/dL
  • Platelets >= 100,000/mcL
  • Total bilirubin < 1.5 mg/dL
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) or serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 x institutional upper limit of normal (ULN) in the absence of hepatic metastasis; SGPT (ALT) =< 3 x ULN or SGOT (AST) =< 5 x ULN in the presence of hepatic metastasis
  • Creatinine =< 1.5 x ULN
  • International normalized ratio (INR) =< 1.4 for patients not on warfarin (Coumadin)
  • INR range of 2.0-3.0 for patients on therapeutic doses of warfarin (Coumadin)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Ability to provide informed consent
  • Willingness to return to a Mayo Clinic institution for follow up
  • Life expectancy >= 84 days (12 weeks)
  • Women of childbearing potential only: negative serum pregnancy test done =< 7 days prior to registration

Exclusion Criteria:

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes or with hemoglobin A1c (HbA1C) > 8, or psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following prior therapies:

    • Chemotherapy =< 28 days prior to registration
    • Mitomycin C/nitrosoureas =< 42 days prior to registration
    • Immunotherapy =< 28 days prior to registration
    • Biologic therapy =< 28 days prior to registration
    • Radiation therapy =< 28 days prior to registration
    • Radiation to > 25% of bone marrow
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • New York Heart Association classification III or IV
  • Known central nervous system (CNS) metastases or seizure disorder; patients with known brain metastases that have been successfully treated and stable for > 6 months without requirement for corticosteroids and without seizure activity will be eligible
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • History of myocardial infarction =< 168 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • >= Grade 2 sensory neuropathy
  • >= Grade 2 hypertriglyceridemia
  • >= Grade 2 hypercholesterolemia
  • Patients on medication considered strong cytochrome P450 3A4 (CYP3A4) inducers (efavirenz, nevirapine, carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort) or CYP3A4 inhibitors (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, telithromycin) unless the medication can be substituted with another agent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01375829

United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Keith Bible Mayo Clinic

Responsible Party: National Cancer Institute (NCI) Identifier: NCT01375829     History of Changes
Obsolete Identifiers: NCT02344147
Other Study ID Numbers: NCI-2012-02907
NCI-2012-02907 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1013 ( Other Identifier: Mayo Clinic )
8814 ( Other Identifier: CTEP )
P30CA015083 ( U.S. NIH Grant/Contract )
U01CA069912 ( U.S. NIH Grant/Contract )
UM1CA186686 ( U.S. NIH Grant/Contract )
First Posted: June 17, 2011    Key Record Dates
Last Update Posted: March 5, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Epothilone B
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action