Ixabepilone to Treat Cervical Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Antonio Fojo, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00924066
First received: June 17, 2009
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.

Condition Intervention Phase
Cervical Carcinoma
Cervical Adenocarcinoma
Cervical Adenosquamous Carcinoma
Cervical Carcinoma, Non-SquamousType
Drug: Ixempra (Ixabepilone (BMS-247550) )
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial of Ixabepilone (Ixempra [R], BMS-247550, NSC 710428), an Epothilone B Analog, in Cervical Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Tumor Response (PR + CR) Per RECIST [ Time Frame: Every 6 weeks, up to 15 months ] [ Designated as safety issue: No ]
    Establish the efficacy of the investigational agent Ixabepilone in patients with cervical carcinoma per the Response Evaluation Criteria in Solid Tumors (RECIST) when Ixabepilone is administered as a daily 1 hour infusion on days 1-5 every 3 weeks. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Not evaluable (NE) means the participant was not evaluable because there was not a scan available to compare to the baseline scan.


Secondary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: 61 months ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.


Enrollment: 41
Study Start Date: November 2008
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: 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.
Other Name: BMS-247550

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
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00924066

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Antonio T Fojo, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: Antonio Fojo, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00924066     History of Changes
Obsolete Identifiers: NCT00798928
Other Study ID Numbers: 090037, 09-C-0037
Study First Received: June 17, 2009
Results First Received: March 13, 2014
Last Updated: May 12, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Ixabepilone
BMS-247550
Ixempra
Cervical Cancer
Epothilone

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Uterine Cervical Neoplasms
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Epothilones
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014