Clinical trial NCT00924066: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cervical Carcinoma
Cervical Adenocarcinoma
Cervical Adenosquamous Carcinoma
Cervical Carcinoma, Non-SquamousType
Keywords: Ixabepilone
BMS-247550
Ixempra
Cervical Cancer
Epothilone
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2009-06-18
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Number of Participants With a Tumor Response (PR + CR) Per RECIST
timeFrame: Every 6 weeks, up to 15 months
Secondary outcomes:
measure: Number of Participants With Serious and Non-Serious Adverse Events
timeFrame: Date treatment consent signed to date off study, approximately 61 months
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Antonio T Fojo, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.