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NCT Number: NCT00422097

A Phase I Study of Oral Ixabepilone in Subjects With Advanced Cancer

This study will determine the maximum tolerated dose of oral ixabepilone administered for 5 successive days every 21 days in participants with advanced cancer. The safety, tolerability, and pharmacokinetics of ixabepilone in the body will be studied. In addition, this study will assess preliminary evidence of the effect of food and famotidine on the pharmacokinetics of oral ixabepilone.

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Key information

Conditions

Cancer Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Georgetown University Medical Center Lombardi Cancer Center, Washington D.C., District of Columbia, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Confirmed diagnosis of solid tumor malignancy unresponsive to current treatment options
  • Measurable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors
  • Lapse of at least 1 week since minor surgery and of at least 3 weeks since major surgery and radiation therapy
  • Eastern Cooperative Oncology Group performance status of 0-1
  • Lapse of at least 4 weeks since immunotherapy or chemotherapy
  • Negative pregnancy test result within 72 hours of study drug administration for any woman of childbearing potential (WOCBP)

Exclusion criteria

  • WOCBP unable or unwilling to use birth control during study and for up to 4 weeks after study completion
  • Women who are pregnant or breastfeeding
  • Fertile men not using effective birth control with partners who are WOCBP
  • Gastrointestinal(GI) disease or GI tract surgery that could impact drug absorption
  • Inability to swallow capsules
  • Inability to be venipunctured or to tolerate venous access
  • Known symptomatic brain metastases
  • Common Terminology Criteria for Adverse Events Grade 2 or greater neuropathy or history of Grade 3 or greater neuropathy
  • Psychiatric conditions inhibiting compliance with protocol requirements
  • Uncontrolled medical disorder or active infection that would impair participant's ability to receive protocol therapy or whose control may be jeopardized by the study treatment protocol
  • Inadequate hematologic, hepatic, or renal function
  • History of significant drug allergy
  • Previous exposure to ixabepilone
  • Exposure to any investigational drug or placebo within 4 weeks of enrollment
  • Concurrent chemotherapy regimen
  • Use of cytochrome P4503A4 inhibitors or inducers within 2 weeks of treatment initiation (unless approved by medical monitor)
  • Use of steroids (except as antiemetic)
  • Prisoners or subjects involuntarily detained for treatment

Treatment and study plan

Ixabepilone, 5 mg/d

Drug

Ixabepilone, 5 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.

Ixabepilone, 10 mg/d

Drug

Ixabepilone, 10 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.

Ixabepilone, 15 mg/d

Drug

Ixabepilone, 15 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.

Ixabepilone, 20 mg/d

Drug

Ixabepilone, 20 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.

Ixabepilone, 25 mg/d

Drug

Ixabepilone, 25 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.

Ixabepilone, 30 mg/d

Drug

Ixabepilone, 30 mg, administered orally once daily on Days 1 through 5 every 21 days. Dose increased by 5 mg for each subsequent treatment group until disease progression, unacceptable toxicity, or participant refusal. No dose escalation within each treatment group. On all dosing days in Cycle 1, participants must fast at least 4 hours before and 4 hours after treatment.

Ixabepilone, 25 mg, with famotidine

Drug

Participants crossed over from Cycle 1 to receive famotidine, 40 mg, in an oral dose given 2 hours before ixabepilone, 25 mg, on Day 1 of Cycle 2 only.

Ixabepilone, 25 mg, with food

Drug

Participants consume a low-fat meal starting 30 minutes before dose administration on Day 1 of Cycle 2. Food consumed within 30 minutes. Administration of the total oral dose should not exceed more than 10 minutes from start to finish.

Primary outcomes

  1. Maximum Tolerated Dose (MTD) of Ixabepilone

    Time frame: Days 1 through 21 (Cycle 1)

    MTD is based on Cycle 1 data only and defined as the maximum dose that can be administered to 6 participants with no more than 1 experiencing a dose-limiting toxicity (DLT) (or fewer than one third of participants if more than 6 receive treatment) with at least 2 participants experiencing a DLT at the next higher dose level. DLT=an event, such as neutropenia; thrombocytopenia; Gr 3 or 4 nausea or diarrhea; Gr 3 fatigue or asthenia; transient arthralgia or recalcitrant myalgia; and prolonged recovery from a toxicity, that occurs during the first course of treatment.

  2. Number of Participants With DLTs by Worst Common Terminology Criteria (CTC) Grade

    Time frame: Days 1 through 21 (Cycle 1), continuously

    Adverse events (AEs) graded by CTC version 3. Grade (Gr) 1=mild; Gr 2=moderate; Gr 3=severe; Gr 4=life threatening; Gr 5=Death related to AE. DLT is defined as an event related to ixabepilone that occurs during the first course of treatment. Includes neutropenia; thrombocytopenia; Gr 3 or 4 nausea, vomiting, or diarrhea despite adequate medical intervention and prophylaxis; Gr 3 fatigue or asthenia; transient arthralgia or myalgia unresponsive to medical intervention; any Gr 3 nonhematologic toxicity; and prolonged recovery from a toxicity.

Secondary outcomes

  1. Number of Participants With Death as Outcome, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation

    Time frame: Days 1 through 21 (Cycle 1), continuously

    An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.

  2. Number of Participants With Abnormal Laboratory Values by Worst CTC Grade

    Time frame: Baseline and Days 1, 8, and 15 of Cycle 1 (21 days)

    Lower limit of normal (LLN)=lowest level of normal among all laboratory ranges. Hemoglobin (g/dL): Gr 1: 10.0-<LLN; Gr 2: 8.0-<10.0; Gr 3:6.5-<8.0; Gr 4: 6.5. Leukocytes (c/uL): Gr 1: 3.0-<LLN; Gr 2: 2.0-<3.0; Gr 3: 1.0-<2.0; Gr 4: <1.0. Lymphocytes (c/uL): Gr 1: 0.8-<1.5; Gr 2: 0.5-<0.8; Gr 3: 0.2-<0.5; Gr 4: <0.2. Neutrophils (Absolute)(c/uL): Gr 1: 1.5-<2.0; Gr 2: 1.0-<1.5; Gr 3: 0.5-<1.0; Gr 4: <0.5. Neutrophils + Bands (c/uL): Gr 1: 1.5-<2.0; Gr 2: 1.0-<1.5; Gr 3: 0.5-<1.0; Gr 4: <0.5. Platelet Count (c/uL):Gr 1: 75.0-<LLN; Gr 2: 50.0-<75.0; Gr 3: 25.0-<50.0; Gr 4: <25.0.

  3. Maximum Plasma Concentration (Cmax) of Ixabepilone

    Time frame: Days 1 and 5 of Cycle 1

  4. Time of Maximum Plasma Concentration (Tmax) of Ixabepilone

    Time frame: Days 1 and 5 of Cycle 1

  5. Area Under the Concentration-time Curve in 1 Dosing Interval (AUC[TAU])of Ixabepilone

    Time frame: Days 1 and 5 of Cycle 1

  6. Plasma Half-life (T-Half) of Ixabepilone

    Time frame: Day 5 of Cycle 1

  7. Maximum Plasma Concentration (Cmax) of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts

    Time frame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)

    After the MTD has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they consume a standard lowfat meal starting 30 minutes prior to ixabepilone, 25 mg, administration on Day 1 of Cycle 2 only. Meal is consumed within a 30-minute period. Administration of the total oral dose should not exceed more than 10 minutes from start to finish.

  8. Time of Maximum Plasma Concentration (Tmax)of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts

    Time frame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)

    After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they consume a standard lowfat meal starting 30 minutes prior to ixabepilone, 25 mg, administration on Day 1 of Cycle 2 only. Meal is consumed within a 30-minute period. Administration of the total oral dose should not exceed more than 10 minutes from start to finish.

  9. Area Under the Curve in 1 Dosing Interval (AUC[TAU]) of Oral Ixabepilone at MTD in Fasted and Fed Participants in Crossover Cohorts

    Time frame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)

    After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they consume a standard lowfat meal starting 30 minutes prior to ixabepilone, 25 mg, administration on Day 1 of Cycle 2 only. Meal is consumed within a 30-minute period. Administration of the total oral dose should not exceed more than 10 minutes from start to finish.

  10. Maximum Plasma Concentration (Cmax) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts

    Time frame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)

    After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they receive famotidine, 40 mg. Prior to dosing on Day 1 of Cycle 2, famotidine administered in an oral dose 2 hours before ixabepilone 25-mg dose.

  11. Time of Maximum Plasma Concentration (Tmax) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts

    Time frame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)

    After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they receive famotidine, 40 mg. Prior to dosing on Day 1 of Cycle 2, famotidine administered in an oral dose 2 hours before ixabepilone 25-mg dose.

  12. Area Under the Curve in 1 Dosing Interval (AUC[TAU]) of Oral Ixabepilone With and Without Famotidine in Crossover Cohorts

    Time frame: Up to 24 hours postdose Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (21 days)

    After the ixabepilone MTD (25 mg) has been defined, participants who completed Cycle 1 (ixabepilone, 25 mg, given alone once daily orally on Days 1 through 5 of 21-day cycle, with participants fasting at least 4 hours before and 4 hours after treatment on all dosing days) then cross over to Cycle 2, during which they receive famotidine, 40 mg. Prior to dosing on Day 1 of Cycle 2, famotidine administered in an oral dose 2 hours before ixabepilone 25-mg dose.

  13. Number of Participants With Significant Findings on Physical Examination or Electrocardiogram (ECG)

    Time frame: At screening and predose Day 1, Cycle 1 (21 days)

    Physical examination evaluated height, weight, Eastern Cooperative Oncology Group performance status, adverse events, and abnormal laboratory findings and included a neurologic examination to evaluate deep tendon reflexes, sensory modalities, and motor strength. Participants also underwent a 12-lead ECG screening. Physical examination findings and ECG findings were considered clinically significant at the investigator's discretion.

  14. Number of Participants With Abnormal (CTC Grade 3 or Greater) Serum Chemistry Levels

    Time frame: At screening and predose Day 1, Cycle 1 (21 days)

    Upper limit of normal (ULN)=upper level of normal among all laboratory ranges. Alkaline phosphatase(U/L): Gr 3: >5.0-20.0*ULN; Gr 4: >20.0*ULN. Sodium (mEq/L): Gr 3: 120-<130 or >155-160; Gr 4 <120. Potassium (mEq/L): Gr 3: 2.5-<3.0 or >6.0-7.0; Gr 4: <2.5 or >7.0. Calcium (mg/dL): Gr 3: 6.0-<7.0 or >12.5-13.5; Gr 4: <6.0 or >13.5. Inorganic phosphorus (mg/dL): Gr 3: 1.0-<2.0; Gr 4: <1.0. Albumin (g/dL): Gr 3: <2.0.

Sponsors and collaborators

Lead sponsor

R-Pharm

Industry

Registry information

Official study title

A Phase I Study of Ixabepilone Administered as a Daily Oral Dose on 5 Successive Days Every 21 Days in Subjects With Advanced Cancer

Important dates

Study start
2007
Primary completion
2009
Study completion
2011
First posted
Jan 15, 2007
Registry last updated
Mar 10, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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