A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer (IXAMPLE2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00883116
First received: April 16, 2009
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

The primary purpose of this study is to investigate whether administration of ixabepilone results in superior outcome as assessed by overall survival compared with that achieved with standard chemotherapy (paclitaxel or doxorubicin) in women with advanced endometrial cancer that has progressed following first-line chemotherapy.


Condition Intervention Phase
Endometrial Cancer
Drug: Ixabepilone
Drug: Doxorubicin
Drug: Paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Open Label, Randomized, 2 Arm Study of Ixabepilone Administered Every 21 Days Versus Paclitaxel or Doxorubicin Administered Every 21 Days in Women With Advanced Endometrial Cancer Who Have Previously Been Treated With Chemotherapy

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Date of randomization to date of death or last date censored to up to approximately 26 months ] [ Designated as safety issue: No ]
    Survival was defined as the time from the date of randomization until the date of death. If the patient did not die, OS was censored on the last date he or she was known to be alive.


Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: Date of randomization to date of disease progression or death (or date of last tumor assessment for those who did not die or progress) up to approximately 22 months ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time from randomization to the date of documented disease progression. Patients who died without a reported prior progression were considered to have progressed on the date of their death. Those who did not progress or die were censored on the date of their last tumor assessment. Participants who did not have any on-study tumor assessments were censored on the date they were randomized. Measurable disease was present if the patient had o1 or more measurable lesions.

  • Best Overall Response Rate [ Time Frame: Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189) ] [ Designated as safety issue: No ]
    Best overall response rate was defined as the number of participants whose best response was either partial response (PR) or complete response (CR) divided by the number of participants in the treatment group. Overall tumor response was based on an integration of the evaluation of target, nontarget, and new lesions. CR=Disappearance of all clinical and radiologic evidence of target lesions. PR=At least 30% reduction in the sum of diameters of all target lesions; taking as reference the baseline study measurement. Changes in tumor measurements need not be confirmed by repeat measurements performed after the criteria for response were first met.

  • Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug [ Time Frame: From Day 1, first dose to 30 days past last dose, up to Day 219 (9 cycles, or 189 days, + 30 days) ] [ Designated as safety issue: Yes ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related to study drug=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.


Enrollment: 500
Study Start Date: August 2009
Study Completion Date: December 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ixabepilone, 40 mg/m^2, intravenously (IV)
Participants received ixabepilone, 40 mg/m^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression
Drug: Ixabepilone
Other Names:
  • Ixempra
  • BMS-247550
Active Comparator: Control chemotherapy (Paclitaxel or Doxorubicin)
Participants received either paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.
Drug: Doxorubicin
Other Names:
  • Adriamycin PFS/RDF
  • Adriacin
  • Adriblastina
  • Adriablastine
  • Adrimedac
  • DOXO-CELL
  • Doxolem
  • Doxorubin
  • Farmiblastina
  • Rubex
Drug: Paclitaxel
Other Names:
  • Taxol
  • Anzatax
  • Asotax
  • Bristaxol Praxel
  • Taxol Konzentrat
  • F1-106

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria

  • Women aged 18 years and older
  • Histologic or cytologic diagnosis of endometrial carcinoma
  • Evidence that the cancer is advanced, recurrent, or metastatic and not curable by local measures, such as surgery or radiation.
  • Karnofsky performance status >=70
  • Measurable or nonmeasurable disease that has progressed since last treatment.

    • If only disease is confined to a solitary lesion, its neoplastic nature must be confirmed by histology or cytology.
    • Disease in a previously irradiated field is acceptable as the only site of measurable disease only if there has been clear progression since completion of radiotherapy.
  • All therapy directed at endometrial cancer must be discontinued 21 days prior to start of treatment, except for hormonal therapy which must be discontinued at least 1 week prior to start of study treatment. Concurrent administration of hormone replacement therapy is allowed.
  • Prior therapy: Participants must have failed 1 prior platinum-based chemotherapeutic regimen for endometrial cancer. May have received 2 prior chemotherapy regimens if 1 regimen was given for stage I or II disease. May have received any number of prior non-cytotoxic regimens such as monoclonal antibodies, cytokines, signal transduction inhibitors, or hormonal therapy. Previous radiation therapy is allowed.

Key Exclusion Criteria

  • Carcinosarcoma (malignant mixed mullerian tumor)
  • Endometrial leiomyosarcoma and endometrial stromal sarcomas
  • Participants who received no prior chemotherapy for endometrial cancer or ≥2 prior chemotherapy regimens (exceptions defined in protocol)
  • Known brain metastases
  • Receipt of prior ixabepilone therapy
  • Concurrent active infection requiring antibiotics or other therapy
  • Concurrent unstable disease or other debilitating illness, such as congestive heart failure, unstable angina, myocardial infarction, or other cardiac disease that could jeopardize participation, within the last 6 months
  • For participants whose prior therapy did not include an anthracycline and therefore may be randomized to doxorubicin, left ventricular ejection fraction <50% as measured by multigated radionuclide angiography or echocardiography
  • History of malignancy, except nonmelanoma skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast, within the last 5 years that has not been treated with chemotherapy
  • Known human immunodeficiency viral infection
  • Psychiatric disorders or other conditions rendering the participant incapable of complying with protocol requirements
  • Absolute neutrophil count <1500/mm^3
  • Platelets <100,000/mm^3
  • Hemoglobin <9 g/dL
  • Total bilirubin >1.5*upper limit of normal (ULN), except for those with Gilbert's disease
  • Aspartate aminotransferase or alanine aminotransferase >2.5*ULN
  • Serum creatinine >1.5*ULN
  • Grade ≥2 neuropathy (sensory or motor)
  • No concurrent therapy (chemotherapy, hormonal, or investigational) directed at endometrial cancer during the study
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00883116

  Show 93 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00883116     History of Changes
Other Study ID Numbers: CA163-196, 2008-007167-16
Study First Received: April 16, 2009
Results First Received: December 6, 2013
Last Updated: February 12, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Brazil: National Health Surveillance Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Greece: Ethics Committee
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Korea: Food and Drug Administration
Mexico: Federal Commission for Sanitary Risks Protection
Norway: Directorate of Health
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Poland: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Taiwan: National Bureau of Controlled Drugs
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Epothilones
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 14, 2014