Protocol Number: 09-C-0037

Title:

A Phase II Clinical Trial of Ixabepilone (Ixempra, BMS-247550, NSC 710428), an Epothilone B Analog, in Cervical Cancer

Number:

09-C-0037

Summary:

Background

- Ixabepilone (Ixempra (Trademark), BMS-247550, NSC 710428) is a semi-synthetic analog of the natural product epothilone B.

- The epothilones are a novel class of non-taxane microtubule-stabilizing agents obtained from the fermentation of the cellulose degrading myxobacteria, Sorangium cellulosum.

- Ixabepilone is active against cancer models that are naturally insensitive to paclitaxel or have developed resistance to paclitaxel, both in-vitro and in-vivo.

Objectives

Primary-

- Establish the efficacy of the investigational agent ixabepilone in patients with cervical carcinoma when administered as a daily one hour infusion on day 1 to 5 every three weeks, as measured by overall response (PR+CR).

Secondary-

- Assess pharmacodynamic endpoints to determine the extent of tubulin polymerization and whether or not there has been activation of cellular death pathways distal to the target.

- Estimate progression free survival and duration of response.

Eligibility

- Age greater than 18

- Histologic or cytologic confirmation of cervical carcinoma; either squamous cell or non-squamous consisting of cervical adenocarcinoma, cervical adenosquamous carcinoma or cervical carcinoma, non-squamous type.

Design

- Phase II study, open, non-randomized

- Ixabepilone will be administered at a dose of 6mg/m(2) daily on days 1 through 5, every three weeks.

- Restaging will be done every two cycles using RECIST

- Planned maximum enrollment 76 persons

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Female

Referral Letter Required: No

Population Exclusion(s): Male

Children

Eligibility Criteria:

INCLUSION CRITERIA:

Patients must fulfill all of the following criteria to be eligible for study admission:

1. Age greater than or equal to 18 years.

2. Histologic or cytologic confirmation of cervical carcinoma, squamous or non-squamous. Within the non-squamous cohort is adenocarcinoma and adenosquamous as well as non-squamous (not otherwise specified).

3. Subjects with unresectable recurrent cervical cancer are eligible.

4. Measurable disease that can be assessed using RECIST criteria.

5. Performance Status ECOG 0-2.

6. Life expectancy of 3 months or greater.

7. Suitable candidate for receiving planned therapy as evidenced by screening laboratory assessments of hematologic, renal, hepatic, and metabolic functions: platelet count greater than or equal to 75,000/mm(3), absolute granulocyte count (AGC) greater than or equal to 1,000/mm(3), serum creatinine less than or equal to 1.6 or a measured creatinine clearance greater than or equal to 40 ml/min, SGPT and SGOT less than or equal to 2.5 x NL, and total bilirubin less than or equal to 1.5 x NL (in patients with clinical evidence of Gilberts' disease, less than or equal to 3 x NL).

Note: A diagnosis of Gilbert's disease will be made in the presence of (1) unconjugated hyperbilirubinemia noted on several occasions; (2) normal results from CBC count, reticulocyte count, and blood smear; (3) normal liver function test results; and (4) an absence of other disease processes that can explain the unconjugated hyperbilirubinemia.

8. Greater than or equal to 4 weeks from prior radiation, intravenous chemotherapy or immunotherapy; greater than or equal to 6 weeks from prior nitrosourea; greater than or equal to 2 weeks from a prior phase 0 study .

9. No serious intercurrent medical illness.

10. The ability to understand and willingness to sign a written informed consent form, and to comply with the protocol.

11. Prior therapy with cisplatin or carboplatin is required.

EXCLUSION CRITERIA:

Patients with any of the following will be excluded from study entry:

1. Pregnant or nursing women are not eligible; neither are women of childbearing potential unless using effective contraception as determined by the patient's physician.

2. Patients with a history of CNS metastases, because symptoms/signs of progressive disease may be confused with drug-related toxicities, unless control has been achieved with either radiation or surgical resection at least six months prior to enrollment on study.

3. Patients who are poor medical risk because of other non malignant systemic disease or active, uncontrolled infection.

4. HIV positive patients not requiring anti-retroviral therapy will be considered for eligibility. Those requiring anti-retroviral therapy will not be eligible.

5. Prior craniospinal radiation, or total body irradiation (TBI).

6. Patients receiving other investigational drugs, or strong CYP3A3 inhibitors (see Section 3.6 for details) that cannot be discontinued or substituted.

7. CTCAE Grade 2 or greater motor or sensory neuropathy.

8. Known prior severe hypersensitivity reactions to agents containing Cremophor(Trademark) EL.

9. Women with localized disease who are potentially curable through surgical resection.

Special Instructions:

Currently Not Provided

Keywords:

Ixabepilone

BMS-247550

Ixempra

Cervical Cancer

Epothilone

Recruitment Keyword(s):

Cervical Cancer

Condition(s):

Cervical Carcinoma

Cervical Adenocarcinoma

Cervical Adenosquamous Carcinoma

Cervical Carcinoma, non-squamous type

Investigational Drug(s):

Ixempra (Ixbepilone (BMS-247550) )

Investigational Device(s):

None

Intervention(s):

Drug: Ixempra (Ixbepilone (BMS-247550) )

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Parkin DM, L��r� E, Muir CS. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer. 1988 Feb 15;41(2):184-97.

Lev�que J, Laurent JF, Burtin F, Foucher F, Goyat F, Grall JY, Meunier B. Prognostic factors of the uterine cervix adenocarcinoma. Eur J Obstet Gynecol Reprod Biol. 1998 Oct;80(2):209-14.

Alfsen GC, Kristensen GB, Skovlund E, Pettersen EO, Abeler VM. Histologic subtype has minor importance for overall survival in patients with adenocarcinoma of the uterine cervix: a population-based study of prognostic factors in 505 patients with nonsquamous cell carcinomas of the cervix. Cancer. 2001 Nov 1;92(9):2471-83.

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