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Dose-Escalation Safety and Pharmacokinetic Study of Iso-Fludelone in Patients With Advanced Solid Tumors

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: NCT01379287
Recruitment Status : Active, not recruiting
First Posted : June 23, 2011
Last Update Posted : June 5, 2018
University of Pittsburgh
Bristol-Myers Squibb
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:

Iso-fludelone is a type of chemotherapy drug called an epothilone. Epothilones are drugs that attach to proteins in your body called "tubulins". Tubulins help cells to grow, and are found in both normal and cancer cells. When research animals with cancer were given the study drug, Iso-fludelone, the drug attached itself to "tubulin" and slowed or stopped the cancer cells from growing. Other types of epothilones have been tested in cancer patients and were found to be safe. A similar epothilone drug and other drugs called taxanes are currently approved by the FDA for treating certain types of cancers.

The purpose of this study is to see the effects, good and/or bad, of this investigational drug, Iso-fludelone, on cancer. The term "investigational" means the study drug being tested has not been approved by the United States Food and Drug Administration (FDA) or other regulatory agencies. This study is the first time the investigators are using iso-fludelone in people. This is a Phase I study. In a Phase I study, the first people to receive the drug are given a fairly low dose.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Iso-Fludelone Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Dose-Escalation Safety and Pharmacokinetic Study of Iso-Fludelone in Patients With Advanced Solid Tumors
Actual Study Start Date : June 2011
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Arm Intervention/treatment
Experimental: Patients with Advanced Solid Tumors
The trial was initially designed as a 3 hour IV infusion of iso-fludelone every 3 weeks with three dose-escalation stages (12 patients), however it has been amended to study iso-fludelone administered over 6 hours (+/- 30 minutes) every 3 weeks schedule.
Drug: Iso-Fludelone
Iso-fludelone will be administered IV over 6 hours (+/- 30 mins) on Day 1 of every 3 week cycle.
Other Name: KOS-1803

Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD) [ Time Frame: 2 years ]
    The MTD is defined as the dose that results in DLT in 25% of all evaluable patients.

  2. To determine the dose limiting toxicity (DLT), safety [ Time Frame: 2 years ]
    Toxicities and adverse events will be assessed using the NCI CTC version 4.0

Secondary Outcome Measures :
  1. To evaluate the plasma pharmacokinetics of iso-fludelone when administered intravenously [ Time Frame: over 6 hours (+/- 30 minutes) on a day 1 every 21 days schedule ]
    All PK analyses will be performed using the WinNonlin computer program; version 5.3 Pharsight Corporation, Mountain View, CA). PK Model selection will be based on a visual inspection of goodness of fit plots (observations vs. predictions, residuals and weighted residuals vs. predictions). The assay values (concentrations vs times) will be used to calculate individual-specific elimination rate constant (Ke), time to maximum Iso-fludelone concentration (Tmax), maximum Iso-fludelone concentration (Cmax) and area under the concentration-time curve (AUC) values.

  2. To describe and assess any preliminary evidence of anti-tumor activity of iso-fludelone [ Time Frame: every 6 weeks ]

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.

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

Inclusion Criteria:

  • Pathologic confirmation of malignancy at Memorial Sloan-Kettering Cancer Center
  • Diagnosis of advanced stage, primary or metastatic adult solid tumors refractory to standard therapy or for which no curative standard therapy exists
  • Evidence of radiographically measurable or non-measurable disease by RECIST 1.1 criteria.
  • All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) Grade ≤1
  • Age must be ≥ 18 years
  • Last dose of antineoplastic therapy except for hormonal therapy must be > 21 days.
  • Patients with brain metastasis that have been treated and clinically stable following intervention with neurological signs or symptoms resolved to CTCAEv4 Grade ≤1
  • ECOG performance status must be 0 or 1.
  • Required baseline laboratory data within 14 days of iso-fludelone administration include
  • Hemoglobin ≥ 8.5 g/dL
  • Absolute neutrophils count ≥ 1.5 x 109 /L
  • Platelet count ≥ 75 x 109 /L
  • Serum bilirubin < or = to 1.5 x ULN
  • AST and ALT < or = to 2.5 x ULN
  • Serum creatinine < or = to 1.5 x ULN
  • Willing and able to comply with scheduled visits, treatment plan, and laboratory tests.

Exclusion Criteria:

  • Pre-existing diarrhea uncontrolled with supportive care. Prior hemorrhagic diarrhea due to ulcerative colitis, inflammatory bowel disease or other cause. Active, uncontrolled peptic ulcer disease (patients maintained with ranitidine or its equivalent are acceptable to enroll).
  • Pre-existing neurological disease (including but not limited to peripheral sensory or motor neuropathy, seizures, gait disturbances, or tremors/involuntary movements) of CTCAEv4 Grade ≥ 2 due to any cause.
  • Hypersensitivity reaction (CTCAEv4 Grade ≥ 2) to prior therapy containing hydroxypropyl-β-cyclodextrin, ethanol, propylene glycol, or patient may not be safely administered ethanol (e.g., current history of ethanol abuse or concomitant administration of Antabuse®).
  • Concurrent therapy with any other investigational agent.
  • Pregnant or breast-feeding women. Female patients must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate. All at-risk female patients must have a negative serum pregnancy test within 10 days prior to the start of study treatment.
  • Clinically significant cardiac disease (New York Heart Association, Class III or IV); prior myocarditis from any cause; pre-existing Grade 2 or higher arrhythmias ("non-urgent medical attention indicated").
  • Dementia or altered mental status that would prohibit informed consent.
  • Patients with untreated central nervous system (CNS) metastases.
  • Patients with known leptomeningeal metastasis
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the patient inappropriate for this study.
  • Pre-existing ophthalmologic conditions (including glaucoma; history of demyelinating disease; vasculitis; retinal vascular occlusion and any optic neuropathy).
  • History (or family history) of long QT syndrome or QTc > 450 msec on baseline ECG.

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): NCT01379287

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United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
University of Pittsburgh
Bristol-Myers Squibb
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Principal Investigator: Mrinal Gounder, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT01379287     History of Changes
Other Study ID Numbers: 10-202
First Posted: June 23, 2011    Key Record Dates
Last Update Posted: June 5, 2018
Last Verified: June 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:

Additional relevant MeSH terms:
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Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents