Phase I Study of Ixabepilone Plus Lapatinib With or Without Capecitabine in the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

NCT00634088 | Terminated Phase 1 Results

• 2 other identifiers: CA163-144EURDRACT: 2007-004123-38
• Study Type: interventional
• Target: 13
• Locations: 3 countries
• Sites: 3

Brief Summary

The purpose of this study is to determine the safety and preliminary effectiveness of ixabepilone plus lapatinib with and without capecitabine in the treatment of human epidermal growth factor receptor 2 (HER2)-positive or metastatic breast cancer.

Conditions

Locally Advanced or Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of Ixabepilone When Administered With Lapatinib

  The MTD is defined as the maximum dose that can be administered to 6 participants such that no more than 1 (or fewer than one third if more than 6 participants receive treatment) experiences a dose-limiting toxicity (DLT), with at least 2 experiencing a DLT at the next higher dose level. The RP2D is based on the MTD and the assessment of any relevant chronic toxicities.

  Days 1 through 21

• MTD and RP2D of Ixabepilone When Administered With Lapatinib Plus Capecitabine

  MTD is defined as the maximum dose that can be administered to 6 participants such that no more than 1 (or fewer than one third if more than 6 participants receive treatment) experiences a DLT, with at least 2 experiencing a DLT at the next higher dose level. The RP2D is based on the MTD and the assessment of any relevant chronic toxicities.

  Days 1 through 21

Secondary Outcomes (11)

• Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)

  Baseline to Day 21, continuously

• Number of Participants With DLT

  Baseline to Day 21, continuously

• Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade

  Baseline and weekly from Days 1 to 21 (Cycle 1)

• Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade

  At baseline and within 72 hours of Day 1 of 21-day cycle

• Maximum Concentration of Ixabepilone

  Day 1 of 21-day cycle

Study Arms (4)

Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg

EXPERIMENTAL

Dose Level 1

Drug: Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg

Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg

EXPERIMENTAL

Dose Level 2

Drug: Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg

Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg

EXPERIMENTAL

Dose Level 3

Drug: Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg

Ixabepilone + Lapatinib + Capecitabine

EXPERIMENTAL

Triplet Combination

Drug: Ixabepilone + Lapatinib + Capecitabine

Interventions

Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg DRUG

Lapatinib, 1000 mg, administered orally, once a day, every day, for 7 to 14 consecutive days as a lead-in period prior to the first administration of ixabepilone (Day 1). Following the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1000 mg, administered orally, once a day, every day, for a 21-day cycle.

Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg

Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg DRUG

Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1000 mg). Lapatinib, 1250 mg, administered orally once a day, every day, for 7 to 14 consecutive days as a lead-in period prior to the first administration of ixabepilone. Following the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib administered, 1250 mg, orally, once a day, every day, for a 21-day cycle.

Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg

Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg DRUG

Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1250 mg). Lapatinib, 1250 mg, administered orally once a day, every day, for 7 to 14 consecutive days as a lead-in period prior to the first administration of ixabepilone. Following the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered orally, once a day, every day, for a 21-day cycle.

Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg

Ixabepilone + Lapatinib + Capecitabine DRUG

Planned escalating doses of the triplet combination of ixabepilone, lapatinib, and capecitabine. No participants were enrolled in this arm due to premature termination of the study.

Ixabepilone + Lapatinib + Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females aged 18 years or older with histologic or cytologic diagnosis of adenocarcinoma originating in the breast
• Radiologic or pathologic evidence that the cancer is metastatic or locally advanced (a T4 tumor and stage IIIB/IIIC disease) and not curable by local measures, such as radiation or surgery
• Positive status for human epidermal growth factor receptor 2
• Measurable disease as per Response Evaluation Criteria In Solid Tumors guidelines
• Karnofsky performance status of 70 to 100
• Life expectancy of at least 3 months

You may not qualify if:

• Prior radiation must not have included 30% or more of major bone-marrow containing areas, such as the pelvis and lumbar spine
• Common Terminology Criteria Grade 2 or greater neuropathy
• Inadequate hematologic, hepatic, or renal function
• Known prior severe hypersensitivity reactions to agents containing Cremophor® EL or known hypersensitivity or prior intolerance to fluoropyrimidine
• Known or suspected dihydropyrimidine dehydrogenase deficiency
• More than 3 prior chemotherapy regimens in the metastatic setting
• Prior treatment with an epothilone or lapatinib; prior treatment with capecitabine within the past 6 months

Sponsors & Collaborators

• R-Pharm: lead
• GlaxoSmithKline: collaborator

Study Sites (3)

The Cancer Institute Of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Local Institution

Brisbane, Queensland, 4101, Australia

Location

Local Institution

Modena, 41100, Italy

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ixabepilone; Lapatinib; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2008
• First Posted: March 12, 2008
• Study Start: June 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: March 10, 2016
• Results First Posted: May 3, 2011

Record last verified: 2016-02

Locations

IT (1); US (1); AU (1)