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

• Register: ClinicalTrials.gov
• Last refreshed on: 18 March 2024
• Main ID: NCT01375829
• Date of registration: 16/06/2011
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Ixabepilone and Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
• Scientific title: Phase I Study of Ixabepilone and Temsirolimus in Adult Patients With Advanced Solid Tumors
• Date of first enrolment: June 27, 2011
• Target sample size: 22
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01375829
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Keith C Bible
• Affiliation: Mayo Clinic

Key inclusion & exclusion 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
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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Adult Solid Neoplasm

Intervention(s)

Drug: Temsirolimus

Other: Pharmacological Study

Drug: Ixabepilone

Primary Outcome(s)

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(s)

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]

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]

Incidence of overall toxicity graded according to Common Toxicity Criteria standard grading [Time Frame: Up to 3 months]

Time to progression [Time Frame: Up to 3 months]

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]

Time until hematologic nadirs (white blood cells, absolute neutrophil count, platelets) [Time Frame: Up to 3 months]

Time until any treatment related toxicity [Time Frame: Up to 3 months]

Time until treatment related grade 3+ toxicity [Time Frame: Up to 3 months]

Secondary ID(s)

8814

NCI-2012-01136

U01CA069912

CDR0000702380

MC1013

P30CA015083

UM1CA186686

NCI-2011-01140

NCI-2012-02907

Source(s) of Monetary Support

Please refer to primary and secondary sponsors