Trial of Dasatinib Plus Ixabepilone in 2nd or 3rd Line Metastatic Breast Cancer

NCT00924352 | Completed Phase 1 Results

• 1 other identifier: ALSSMBC0804
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 13

Brief Summary

The primary objective for the Phase I portion of the study is to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) and for the Phase II portion of the study is to evaluate progression free survival (PFS). Secondary objectives are response rate, clinical benefit rate, and overall toxicity.

Conditions

Metastatic Breast Cancer

Keywords

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (4)

• Determination of the Maximum Tolerated Dose (MTD) of Dasatinib When Given in Combination With Ixabepilone (Phase I)

  The MTD of dasatinib (taken daily, continuously) when given in combination with ixabepilone (administered on Days 1, 8, and 15 of a 28-day cycle) was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. The MTD was defined as the dose at which ≤ 1 of 6 patients experienced DLT, and above which ≥ 2 of 6 patients experienced DLT.

  MTD was assessed during the first cycle of combination therapy (days 1-28).

• Determination of the Maximum Tolerated Dose (MTD) of Ixabepilone When Given in Combination With Dasatinib (Phase I)

  The MTD of ixabepilone (administered on Days 1, 8, and 15 of a 28-day cycle) when given in combination with dasatinib (taken daily, continuously) was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. The MTD was defined as the dose at which ≤ 1 of 6 patients experienced DLT, and above which ≥ 2 of 6 patients experienced DLT.

  MTD was assessed during the first cycle of combination therapy (days 1-28).

• Determination of the Dose Limiting Toxicities (DLTs) of the Combination of Dasatinib and Ixabepilone (Phase I)

  DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose limiting toxicity was defined as any grade 4 hematologic event or any grade 3 or 4 non-hematologic event occurring during cycle 1 that is attributable to dasatinib, ixabepilone, or the combination. The following events were excluded from this definition: grade 4 neutropenia lasting for 3 days or less; grade 3 nausea responsive to antiemetics; grade 3 infection with normal ANC or grade 1 or 2 neutrophils; grade 3 diarrhea responsive to optimal use of antidiarrheal therapy.

  DLTs were assessed during the first cycle of combination therapy (days 1-28).

• Evaluation of Progression-free Survival (PFS) of the Combination of Dasatinib and Ixabepilone (Phase II)

  Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.

  PFS was measured from day 1 of treatment until time of progression (assessed about every 8 weeks) or death, whichever came first, for up to 27.2 months.

Secondary Outcomes (4)

• Best Overall Response of the Combination of Dasatinib and Ixabepilone (Phase II)

  Response to treatment was assessed after about every 8 weeks of treatment, for up to 27.2 months.

• Clinical Benefit Rate of the Combination of Dasatinib and Ixabepilone (Phase II)

  Response to treatment was assessed after about every 8 weeks of treatment, for up to 27.2 months.

• Incidence of Grade 3 Adverse Events (AEs) With the Combination of Dasatinib and Ixabepilone (Phase II)

  Adverse events were collected beginning on day 1 of treatment until one month after the end of study treatment.

• Incidence of Grade 4 Adverse Events (AEs) With the Combination of Dasatinib and Ixabepilone (Phase II)

  Adverse events were collected beginning on day 1 of treatment until one month after the end of study treatment.

Study Arms (1)

Ixabepilone + Dasatinib

EXPERIMENTAL

Ixabepilone, for injection 15 mg supplied with diluent for ixabepilone, 8 mL. Dose Level 2;20 mg/m2,Dose Level 1;20 mg/m2,Dose Level 0 (Starting Dose);16 mg/m2,Dose Level - 1;12 mg/m2,Dose Level - 2;12 mg/m2. Dasatinib tablets will be administered continuously starting on Day 1, Cycle 1 once daily (QD).Dose Level 2;140 mg QD,Dose Level 1;100 mg QD,Dose Level 0 (Starting Dose);100 mg QD,Dose Level - 1;100 mg QD,Dose Level - 2;70 mg QD.

Drug: Dasatinib; Drug: Ixabepilone

Interventions

Dasatinib DRUG

Dasatinib tablets will be administered continuously starting on Day 1, Cycle 1 once daily (QD).Dose Level 2;140 mg QD,Dose Level 1;100 mg QD,Dose Level 0 (Starting Dose);100 mg QD,Dose Level - 1;100 mg QD,Dose Level - 2;70 mg QD.

Also known as: SPRYCEL

Ixabepilone + Dasatinib

Ixabepilone DRUG

Ixabepilone, for injection 15 mg supplied with diluent for ixabepilone, 8 mL. Dose Level 2;20 mg/m2,Dose Level 1;20 mg/m2,Dose Level 0 (Starting Dose);16 mg/m2,Dose Level - 1;12 mg/m2,Dose Level - 2;12 mg/m2.

Also known as: IXEMPRA

Ixabepilone + Dasatinib

Eligibility Criteria

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

You may qualify if:

• Patient has the ability to understand and the willingness to sign a written informed consent including form according to institutional guidelines.
• Patient has histologically-proven breast cancer.
• Patient has locally recurrent or metastatic disease, measurable or non- measurable by RECIST criteria.
• Patient has HER2-negative disease or disease that is refractory to HER2- directed therapy.
• Patient is female or male ≥ 18 years of age.
• Patient has(ECOG)performance status of ≤ 2.
• Patient must have received at least 1 but no more than 2 prior chemotherapy regimens for locally recurrent or metastatic disease. Patients may have received neoadjuvant and/or adjuvant chemotherapy. These prior regimens can not have included ixabepilone or dasatinib. A line of chemotherapy will be defined as one or more agents used continuously or discontinuously (i.e., allowing a break or chemo holiday) without the addition of a new agent. Hormonal therapy will not be considered a line of therapy.
• Prior chemotherapy must have been completed at least 3 weeks prior to study treatment start (6 weeks for nitrosoureas and mitomycin), and the patient must have recovered from all associated toxicities (except for alopecia and neuropathy grade 1 according to CTCAE, v3.0 classification).
• Radiation therapy, immunotherapy, biologic therapy, and hormonal/endocrine therapy must have been completed at least 2 weeks prior to study treatment start. Any major surgery must have been completed at least 4 weeks prior to study treatment start.
• Patient has adequate organ, metabolic and bone marrow function as follows:
• Total bilirubin ≤ 1.0 × institutional ULN
• AST, ALT ≤ 2.5 × institutional ULN
• Serum sodium, potassium, calcium, magnesium, and phosphate ≥ institutional LLN. (Hypokalemia or hypomagnesemia must be corrected prior to dasatinib administration.)
• Serum creatinine \< 1.5 × institutional ULN
• Hematologic function: - ANC ≥ 1500/mm3. -Platelet count ≥ 100,000/mm3. - Hemoglobin ≥ 10.0 g/dL

You may not qualify if:

• Patient has had prior treatment with ixabepilone, dasatinib, or both.
• Patient has had more than 2 prior lines of chemotherapy for locally recurrent or metastatic breast cancer. A line of chemotherapy will be defined as one or more agents used continuously or discontinuously (i.e., allowing a break or chemo holiday) without the addition of a new agent. Hormonal therapy will not be considered a line of therapy.
• Patient has received a cumulative dose of \> 360 mg/m2 of doxorubicin or \> 600 mg/m2 of epirubicin.
• Prior radiation must not have included ≥ 30% of major bone marrow containing areas (pelvis, lumbar spine).
• Patients with CTC grade 2 or greater neuropathy (motor or sensory) at study entry.
• Patient has evidence CNS or brain metastases, unless CNS or brain metastases have been treated and stable for \> 3 months.
• Patient has psychiatric illness or social situation that would limit or prohibit compliance with study requirements.
• Patient has an inability to take oral medication or inability to absorb oral medication.
• Patient has had any invasive cancer other than the one being treated in this study within 3 years with the exception of surgically cured nonmelanoma skin cancer; in situ carcinoma of the cervix; in situ carcinoma of the breast.
• Patient is receiving concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy for cancer).
• Patient has other serious medical conditions as judged by the Principal Investigator.
• Patient has a concurrent medical condition which may increase the risk of toxicity.
• Patient has a pleural or pericardial effusion of any grade.
• Patient has cardiac symptoms including any of the following:
• Uncontrolled angina, congestive heart failure or myocardial infarction within 6 months of study entry.

Sponsors & Collaborators

• Accelerated Community Oncology Research Network: lead
• Bristol-Myers Squibb: collaborator

Study Sites (13)

Hematology Oncology PC

Stamford, Connecticut, 06902, United States

Location

Central Georgia Cancer Care

Macon, Georgia, 31201, United States

Location

Northwest Georgia Oncology Centers

Marietta, Georgia, 30060, United States

Location

North Shore Cancer Research

Skokie, Illinois, 60076, United States

Location

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, 52722, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01107, United States

Location

Hematology Oncology Centers of the Northern Rockies

Billings, Montana, 59101, United States

Location

Oncology Hematology Specialists, P.A.

Denville, New Jersey, 07834, United States

Location

The Moses H. Cone Regional Cancer Center

Greensboro, North Carolina, 27403, United States

Location

North Coast Cancer Care

Sandusky, Ohio, 44870, United States

Location

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

University of Tennessee Cancer Institute

Memphis, Tennessee, 38104, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Dasatinib; ixabepilone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Vice President of Scientific Affairs
• Organization: Vector Oncology (formerly Accelerated Community Oncology Research Network, Inc.)

mwalker@vectoroncology.com

901-435-5570

Study Officials

• Lee S. Schwartzberg, MD, FACP

  The West Clinic

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2009
• First Posted: June 18, 2009
• Study Start: June 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 13, 2014
• Results First Posted: September 29, 2014

Record last verified: 2014-10

Locations

US (13)