| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced, recurrent or metastatic endometrial carcinoma |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10014745 |
| E.1.2 | Term | Endometrial carcinoma metastatic |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10014747 |
| E.1.2 | Term | Endometrial carcinoma recurrent |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the overall survival (OS) in women who have progressive disease after one prior chemotherapy regimen for advanced, recurrent or metastatic endometrial cancer treated with ixabepilone versus control chemotherapy (paclitaxel or doxorubicin). |
|
| E.2.2 | Secondary objectives of the trial |
1) To compare the progression-free survival (PFS) in randomized subjects with measurable disease.
2) To compare the objective response rate (ORR) of ixabepilone versus control chemotherapy in subjects with measurable disease.
3) To estimate the duration of response and time to response of ixabepilone versus control chemotherapy, in responding subjects with measurable disease.
4) To evaluate the toxicity profiles of ixabepilone and control chemotherapy.
For Exploratory Objectives, see protocol section 2.3.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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.
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.
|
|
| E.4 | Principal 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.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is overall survival (OS) evaluated in all randomized subjects.
All subjects treated will be evaluated for safety using the National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) version 3.0 based on recorded adverse events, physical examinations, and clinical laboratory assessments.
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|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Quality of life (QLQ-C30 questionnaire) |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 48 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial will occur when 441 death events have been reported.
This is expected to occur by 31-July, 2013. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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