Ixabepilone to Treat Cervical Cancer

NCT ID: NCT00924066

Last Updated: 2019-11-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2013-12-31

Brief Summary

Background:

• Ixabepilone is a member of the class of drugs called epothilones. These drugs interfere with the ability of cancer cells to replicate.
• Epothilones are similar to taxanes, another class of drugs, which includes the drug Taxol. Taxol is widely used to treat a variety of cancers.
• Ixabepilone can work in cells that are resistant to Taxol.

Objectives:

• To determine whether ixabepilone is effective for treating cervical cancer.

Eligibility:

• Women 18 years of age or older with cervical cancer.

Design:

• Patients receive ixabepilone intravenously (through a vein) over 60 minutes on the first 5 days of each 21-day treatment cycle. Their dosage may be adjusted according to how their bodies respond to the drug.
• The number of cycles each woman receives depends on her response to the treatment.
• Patients have CT (computed tomography) scans and other tests before starting treatment and then every other treatment cycle to determine the response of the tumor to ixabepilone.
• Patients who can undergo a tumor biopsy (surgical removal of a sample of tumor tissue) are asked to have a biopsy done before starting treatment with ixabepilone and again on the fourth or fifth day of treatment. This procedure is optional.

Detailed Description

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 days 1 to 5 every three weeks, as measured by overall response (PR (partial response) +CR (complete response)).

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 (Response Evaluation Criteria in Solid Tumors)
• Planned maximum enrollment 76 persons

Conditions

Cervical Carcinoma; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Carcinoma, Non-SquamousType

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Squamous and Nonsquamous participants

Squamous cell carcinoma is a histologic subtype of cervical cancer. Squamous cell carcinoma of the cervix (80%) is much more common than adenocarcinoma of the cervix.

Non squamous carcinoma is a histologic subtype of cervical cancer. It is the second most common form of cervical cancer; consists of adenocarcinoma, adenosquamous and non squamous (not otherwise specified) subtypes.

All participants in both arms received ixabepilone 6 mg/m^2 x 5 days, each cycle.

Group Type: EXPERIMENTAL

Ixempra (Ixabepilone (BMS-247550) )

Intervention Type: DRUG

Participants received Ixabepilone 6mg/m\^2 for a total of 30mg/m\^2 inpatient or outpatient intravenously over an hour on the first five days of each 21 day cycle.

Interventions

Ixempra (Ixabepilone (BMS-247550) )

Participants received Ixabepilone 6mg/m\^2 for a total of 30mg/m\^2 inpatient or outpatient intravenously over an hour on the first five days of each 21 day cycle.

Intervention Type: DRUG

Other Intervention Names

BMS-247550

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 (Response Evaluation Criteria in Solid Tumors) criteria.

5. Performance Status ECOG (Eastern Cooperative Oncology Group) 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 (serum glutamic pyruvic transaminase) and SGOT (serum glutamic oxaloacetic transaminase) less than or equal to 2.5 times the NL (normal limit), and total bilirubin less than or equal to 1.5 times the NL (in patients with clinical evidence of Gilberts' disease, less than or equal to 3 times the 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 (complete blood count) 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 patients physician.

2. Patients with a history of CNS (central nervous system) 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 three 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. Human Immunodeficiency Virus (HIV) positive patients will be considered for eligibility, as long as they are not receiving antiretroviral drugs with strong CYP3A4 (cytochrome P450 3A4) inhibitory activity.

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 (Common Terminology Criteria for Adverse Events) 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Antonio Fojo, M.D.

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Antonio T Fojo, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Countries

United States

References

Parkin DM, Laara E, Muir CS. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer. 1988 Feb 15;41(2):184-97. doi: 10.1002/ijc.2910410205.

Reference Type: BACKGROUND

PMID: 3338870 (View on PubMed)

Leveque 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. doi: 10.1016/s0301-2115(98)00106-7.

Reference Type: BACKGROUND

PMID: 9846671 (View on PubMed)

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. doi: 10.1002/1097-0142(20011101)92:93.0.co;2-k.

Reference Type: BACKGROUND

PMID: 11745305 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2009-C-0037.html

NIH Clinical Center Detailed Web Page

Other Identifiers

09-C-0037

Identifier Type: -

Identifier Source: secondary_id

090037

Identifier Type: -

Identifier Source: org_study_id

NCT00798928

Identifier Type: -

Identifier Source: nct_alias