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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01375829
First received: June 16, 2011
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: ixabepilone
Drug: temsirolimus
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Ixabepilone and Temsirolimus in Adult Patients With Advanced Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

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

  • 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 ] [ Designated as safety issue: No ]
    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).

  • Time until any treatment related toxicity [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
  • Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
  • Time until hematologic nadirs (white blood cells, absolute neutrophil count, platelets) [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: June 2011
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • BMS-247550
  • epothilone B lactam
  • Ixempra
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

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 therapy, patients are followed up for 3 months.

  Eligibility

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

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 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 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
  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: NCT01375829

Locations
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Michael E. Menefee    904-953-2000    menefee.michael@mayo.edu   
Principal Investigator: Michael E. Menefee         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Keith C. Bible    507-538-7623    bible.keith@mayo.edu   
Principal Investigator: Keith C. Bible         
Sponsors and Collaborators
Investigators
Principal Investigator: Michael Menefee Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01375829     History of Changes
Other Study ID Numbers: NCI-2012-02907, NCI-2012-02907, CDR0000702380, MC1013, 8814, UM1CA186686, U01CA069912, P30CA015083
Study First Received: June 16, 2011
Last Updated: August 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Sirolimus
Everolimus
Epothilone B
Epothilones
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014