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

Phase 3

Recruiting

• Conditions: Advanced Endometrial Cancer; C54.1; C04.588.945.418.948.585

• Registration Number: RBR-7spw98
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-06-21
• Last Update Posted: 29 May 2023

Recruitment & Eligibility

• Status: recruiting
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

All subjects must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional and
federal guidelines.
Histologic or cytologic diagnosis of endometrial carcinoma.
Evidence that the cancer is locally advanced, recurrent or metastatic and not
curable by local measures (ie, surgery, radiation).
Karnofsky performance status (KPS) 70, 80, 90, or 100 (see Appendix 2).
Subjects must have measurable or non-measurable disease (see Section 6.4.3) that
has progressed since last treatment. A maximum of 140 subjects with
non-measurable disease will be randomized.
Notes:
If the subject’s 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. Note: concurrent administration of hormone replacement therapy is allowed.
Subjects must have received one and only one prior chemotherapy (ie, cytotoxic)
regimen for locally advanced, recurrent or metastatic endometrial cancer. Subjects
with 1 additional prior chemotherapy regimen in the neoadjuvant or adjuvant
setting are allowed. Adjuvant/neoadjuvant therapy is defined as post or
preoperative therapy for Stage 1, 2, or 3 disease.
Subjects 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.
Women, ages 18 to 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.
WOCBP include any female who has experienced menarche and who has not
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
Amenorrhea ? 12 consecutive months without another cause or
For women with irregular menstrual periods and on hormone replacement
therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
Women who are using oral contraceptives, other hormonal contraceptives
(vaginal products, skin patches, or implanted or injectable products), or
mechanical products such as an intrauterine device or barrier methods
(diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing
abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.

Exclusion Criteria

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.
Women who are pregnant or breastfeeding.
Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
Carcinosarcoma (malignant mixed mullerian tumor)
Endometrial leiomyosarcoma and endometrial stromal sarcomas.
Subjects with no prior chemotherapy (ie, cytotoxic) for locally advanced,
recurrent or metastatic endometrial cancer or subjects that received 2 or more
prior chemotherapy (ie, cytotoxic) regimens for locally advanced, recurrent or
metastatic endometrial cancer.
Subjects with known brain metastases. Note: brain scans are not required.
Receipt of prior ixabepilone therapy.
Concurrent active infection requiring antibiotics or other therapy.
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.
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).
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.
Known human immunodeficiency viral (HIV) infection.
Psychiatric disorders or other conditions rendering the subject incapable of
complying with the requirements of the protocol.
Absolute neutrophil count (ANC) < 1500/mm3.
Platelets < 100,000/ mm3.
Hemoglobin < 9 g/dL.
Total bilirubin > 1.5 times the institutional upper limit of normal (ULN), except for subjects with Gilbert’s disease.
AST or ALT > 2.5 times the institutional upper limit of normal (ULN).
Serum creatinine > 1.5 x institutional upper limit of normal (ULN).
Grade ? 2 neuropathy (sensory or motor).
Known allergy to any of the study drugs or their excipients such as, prior severe
HSR to agents containing Cremophor® EL.
No concurrent therapy directed at endometrial cancer (chemotherapy, hormonal,
or investigational during the study).
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).
Other concurrent anti-tumor, chemotherapy, hormonal therapy, immunotherapy
regimens or radiation therapy, standard or investigational therapy (see
Section 5.5).
Prisoners or subjects who are involuntarily incarcerated.
Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.

Study & Design

• Study Type: Intervention
• Study Design: Not specified