search
Back to results

Ixabepilone to Treat Cervical Cancer

Primary Purpose

Cervical Carcinoma, Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ixempra (Ixabepilone (BMS-247550) )
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Carcinoma focused on measuring Ixabepilone, BMS-247550, Ixempra, Cervical Cancer, Epothilone

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers
  • 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.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Squamous and Nonsquamous participants

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Participants With a Tumor Response (PR + CR) Per RECIST
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 Serious and Non-Serious Adverse Events
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Full Information

First Posted
June 17, 2009
Last Updated
November 13, 2019
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00924066
Brief Title
Ixabepilone to Treat Cervical Cancer
Official Title
A Phase II Clinical Trial of Ixabepilone (Ixempra [R], BMS-247550, NSC 710428), an Epothilone B Analog, in Cervical Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Why Stopped
Premature closure due to slow/insufficient accrual.
Study Start Date
November 2008 (Actual)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Carcinoma, Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Carcinoma, Non-SquamousType
Keywords
Ixabepilone, BMS-247550, Ixempra, Cervical Cancer, Epothilone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Squamous and Nonsquamous participants
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ixempra (Ixabepilone (BMS-247550) )
Other Intervention Name(s)
BMS-247550
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With a Tumor Response (PR + CR) Per RECIST
Description
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.
Time Frame
Every 6 weeks, up to 15 months
Secondary Outcome Measure Information:
Title
Number of Participants With Serious and Non-Serious Adverse Events
Description
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame
Date treatment consent signed to date off study, approximately 61 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Patients must fulfill all of the following criteria to be eligible for study admission: Age greater than or equal to 18 years. 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). Subjects with unresectable recurrent cervical cancer are eligible. Measurable disease that can be assessed using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Performance Status ECOG (Eastern Cooperative Oncology Group) 0-2. Life expectancy of 3 months or greater. 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. 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 . No serious intercurrent medical illness. The ability to understand and willingness to sign a written informed consent form, and to comply with the protocol. Prior therapy with cisplatin or carboplatin is required. EXCLUSION CRITERIA: Patients with any of the following will be excluded from study entry: Pregnant or nursing women are not eligible; neither are women of childbearing potential unless using effective contraception as determined by the patients physician. 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. Patients who are poor medical risk because of other non malignant systemic disease or active, uncontrolled infection. 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. Prior craniospinal radiation, or total body irradiation (TBI). Patients receiving other investigational drugs, or strong CYP3A3 inhibitors (see Section 3.6 for details) that cannot be discontinued or substituted. CTCAE (Common Terminology Criteria for Adverse Events) Grade 2 or greater motor or sensory neuropathy. Known prior severe hypersensitivity reactions to agents containing Cremophor (Trademark) EL. Women with localized disease who are potentially curable through surgical resection.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio T Fojo, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
3338870
Citation
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.
Results Reference
background
PubMed Identifier
9846671
Citation
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.
Results Reference
background
PubMed Identifier
11745305
Citation
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.
Results Reference
background
Links:
URL
http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2009-C-0037.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Ixabepilone to Treat Cervical Cancer

We'll reach out to this number within 24 hrs