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 ChemotherapyRevised Protocol 03, incorporating Amendments 03, 06 and 08 and Administrative Letter 1 (version 6.0 dated 15-Jun-2010)+ Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific (version 2.0, dated 08-Apr-09)

Phase 1

Conditions: Advanced, recurrent or metastatic endometrial carcinoma
MedDRA version: 9.1Level: LLTClassification code 10014745Term: Endometrial carcinoma metastatic
MedDRA version: 9.1Level: LLTClassification code 10014747Term: Endometrial carcinoma recurrent

Registration Number: EUCTR2008-007167-16-BE

Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 410

Inclusion Criteria

1) Signed Written Informed Consent

2) Target Population
a) Histologic or cytologic diagnosis of endometrial carcinoma.
b) Evidence that the cancer is advanced, recurrent or metastatic and not curable by local measures (ie, surgery, radiation).
c) Karnofsky performance status (KPS) 70, 80, 90, or 100 (see Appendix 2).
d) Subjects must have measurable or non-measurable disease (see Section 6.4.3) that has progressed since last treatment. A maximum of 96 subjects with non-measurable disease will be randomized.
Notes:
i) If the subject’s only disease is confined to a solitary lesion, its neoplastic nature must be confirmed by histology or cytology.
ii) 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.
e) 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. Note: concurrent administration of hormone replacement therapy is allowed.

3) Prior therapy
a) Subjects must have failed one prior platinum based chemotherapeutic regimen for
endometrial cancer.
i) Subjects may have received 2 prior chemotherapy (ie, cytotoxic) regimens if
1 regimen was given for stage I or II disease
b) Subjects may have received any number of prior non-cytotoxic regimens such as monoclonal antibodies, cytokines, signal transduction inhibitors, or hormonal therapy.
c) Previous radiation therapy is allowed.

4) Age and Sex
a) Women, ages 18 or older.
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of investigational product.
b) Women who are pregnant or breastfeeding.
c) Women with a positive pregnancy test on enrollment or prior to investigational product administration.

2) Target Disease Exceptions
a) Carcinosarcoma (malignant mixed mullerian tumor)
b) Endometrial leiomyosarcoma and endometrial stromal sarcomas.
c) Subjects who received no prior chemotherapy (ie, cytotoxic), for endometrial
cancer or = 2 prior chemotherapy (ie, cytotoxic) regimens, except as defined in
Protocol Section 4.2.1, Inclusion Criteria
d) Subjects with known brain metastases.
Note: brain scans are not required.

3) Medical History and Concurrent Diseases
a) Receipt of prior ixabepilone therapy.
b) Concurrent active infection requiring antibiotics or other therapy.
c) Concurrent unstable disease or other debilitating illness that could jeopardize participation such as congestive heart failure, unstable angina, myocardial infarction or other cardiac disease within last 6 months.
d) For subjects whose prior therapy did not include an anthracycline (eg, doxorubicin) and therefore may be randomized to doxorubicin, LVEF of < 50% as measured by multi-gated radionuclide angiography (MUGA) or echocardiography (ECHO).
e) History of prior malignancy within last 5 years except non-melanoma skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast not treated with chemotherapy.
f) Known human immunodeficiency viral (HIV) infection.
g) Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocol.

4) Physical and Laboratory Test Findings
a) Absolute neutrophil count (ANC) < 1500/mm³.
b) Platelets < 100,000/ mm³.
c) Hemoglobin < 9 g/dL.
d) Total bilirubin > 1.5 times the institutional upper limit of normal (ULN), except for subjects with Gilbert’s disease.
e) AST or ALT > 2.5 times the institutional upper limit of normal (ULN).
f) Serum creatinine > 1.5 x institutional upper limit of normal (ULN).
g) Grade = 2 neuropathy (sensory or motor).

5) Allergies and Adverse Drug Reactions
a) Known allergy to any of the study drugs or their excipients such as, prior severe HSR to agents containing Cremophor® EL.

6) Prohibited Treatments and/or Therapies
a) No concurrent therapy directed at endometrial cancer (chemotherapy, hormonal, or investigational during the study).
b) Subjects must not continue or institute treatment with the following strong inhibitors of CYP3A4 from 72 hours prior to the initiation of study therapy until end of treatment with ixabepilone or paclitaxel: Ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, or voriconazole (See IB1).
c) Other concurrent anti-tumor, chemotherapy, hormonal therapy, immunotherapy regimens or radiation therapy, standard or investigational therapy (see Section 5.5).

7) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated.
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.