Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Carcinoma, Cervical Carcinoma, Non-SquamousType
Conditions
Keywords
Ixabepilone, BMS-247550, Ixempra, Cervical Cancer, Epothilone
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
Interventions
DRUGIxempra (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.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Tumor Response (PR + CR) Per RECIST | Every 6 weeks, up to 15 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and Non-Serious Adverse Events | Date treatment consent signed to date off study, approximately 61 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | Squamous and Nonsquamous Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants |
| Age, Continuous | 46.79 years STANDARD_DEVIATION 9.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 41 Participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 41 |
| other Total, other adverse events | 41 / 41 |
| serious Total, serious adverse events | 18 / 41 |
Outcome results
Primary
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.
Time frame: Every 6 weeks, up to 15 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Squamous and Nonsquamous Participants | Number of Participants With a Tumor Response (PR + CR) Per RECIST | Not Evaluable (only 1 cycle) | 2 Participants |
| Squamous and Nonsquamous Participants | Number of Participants With a Tumor Response (PR + CR) Per RECIST | Progressive Disease | 25 Participants |
| Squamous and Nonsquamous Participants | Number of Participants With a Tumor Response (PR + CR) Per RECIST | Stable Disease | 10 Participants |
| Squamous and Nonsquamous Participants | Number of Participants With a Tumor Response (PR + CR) Per RECIST | Partial Response | 4 Participants |
| Squamous and Nonsquamous Participants | Number of Participants With a Tumor Response (PR + CR) Per RECIST | Complete Response | 0 Participants |
Secondary
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.
Time frame: Date treatment consent signed to date off study, approximately 61 months
Population: Adverse events are grouped together because the histology cohort has no bearing on the adverse events.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Squamous and Nonsquamous Participants | Number of Participants With Serious and Non-Serious Adverse Events | 41 Participants |