Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Adenocarcinoma

Uterine Cervical Neoplasms

Carcinoma, Adenosquamous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Epothilones

Epothilone B

Tubulin Modulators

Antimitotic Agents

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.

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.

Ixempra (Ixabepilone (BMS-247550) )

Antonio T Fojo, M.D.

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.

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

Ixabepilone to Treat Cervical Cancer

A Phase II Clinical Trial of Ixabepilone (Ixempra [R], BMS-247550, NSC 710428), an Epothilone B Analog, in Cervical Cancer

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.

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.

National Cancer Institute (NCI)

Principal Investigator

Adverse Events for Squamous and Non-squamous Participants

Squamous and Nonsquamous Participants

Age, Continuous

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Antonio Fojo, M.D.

Not Evaluable (only 1 cycle)

Progressive Disease

Stable Disease

Partial Response

Complete Response

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.

Number of Participants With a Tumor Response (PR + CR) Per RECIST

Adverse events are grouped together because the histology cohort has no bearing on the adverse events.

Number of Participants With Serious and Non-Serious Adverse Events

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (40mg/m\^2)

Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (32mg/m\^2)

Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m\^2)

Dose Level 1 - Sorafenib PO BID (200mg) Dose Level -1 - Sorafenib PO BID (200mg) Dose Level 1a - Sorafenib PO BID (400mg)

Dose Level 1 - Ixabepilone IV every 21 days (40mg/m\^2) Dose Level -1 - Ixabepilone IV every 21 days (32mg/m\^2) Dose Level 1a - Ixabepilone IV every 21 days (32mg/m\^2)

Ixabepilone

Denise A. Yardley, M.D.

In this study, patients with metastatic HER2-negative breast cancer will receive treatment with ixabepilone and sorafenib until disease progression or unacceptable toxicity occurs. The Phase I portion of this study will determine the maximum tolerated doses (MTDs) of sorafenib and ixabepilone that may be used in combination for first- or second-line treatment of MBC. The MTDs identified in the Phase I portion of the study will be used in the Phase II portion which will evaluate the efficacy and safety of the combination of sorafenib and ixabepilone in patients who have received at least one prior chemotherapy treatment in either the adjuvant or neoadjuvant setting or following one prior MBC chemotherapy in MBC patients who had not received prior adjuvant or neoadjuvant breast cancer chemotherapy. This will be one of the initial trials investigating the use of this treatment combination for MBC.

This trial will be conducted under the leadership of the Sarah Cannon Research Institute (SCRI) Oncology Research Consortium, a community-based, multi-center, clinical trial organization.

Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer

Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer (MBC)

Measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) - progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Measured from Day 1 of study drug administration to disease progression as defined by RECIST v1.1, or death on study. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Objective Response will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST).

Measured from Day 1 of study drug administration to date of death due to any cause.

Assessments are made through analysis of reported incidence of treatment-emergent AEs and SAEs.

Bayer

Bristol-Myers Squibb

SCRI Development Innovations, LLC

Includes patients treated at the Phase II dose - Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m\^2)

Dose Level 1a

Patients treated at all dose levels in the Phase I and Phase II portions of the study

: Dose Level 1 (4 patients) Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (40mg/m\^2)

Dose Level -1 (3 patients) Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (32mg/m\^2)

Dose Level 1a (76 patients) Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m\^2)

All Patients

John D. Hainsworth, MD

Oral targeted therapy and Systemic Chemotherapy

Sorafenib and Ixabepilone

Includes patients treated at the Phase II dose

Progression-Free Survival (PFS)

6-month Progression-Free Survival

Includes patients treated at the Phase II dose who were evaluable for response

Objective Response Rate

Overall Survival (OS)

Neutropenia

Febrile neutropenia

Anemia

Thrombocytopenia

Fatigue

Nausea/vomiting

Rash

Neuropathy

Anorexia/weight loss

Diarrhea

Arthralgia/myalgia

Alopecia

Pain in extremity

Hypertension

Constipation

Dyspnea

Hand-foot syndrome

Taste alteration

Mucositis

Pruritus

Phase II - Sorafenib and Ixabepilone

Number of Patients With Adverse Events as a Measure of of Safety and Tolerability

Dose Level 1

Dose Level -1

Phase I

Phase II

Antirheumatic Agents

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Systemic Therapy followed by surgery and possible radiation therapy

40 mg/m2 IV infusion over 3 hours on day 1 of a 21 day cycle for 6 cycles

600 mg/m2 IV infusion per institutional guidelines on day 1 of a 21 day cycle for 6 cycles

Denise A Yardley, M.D.

We propose to evaluate ixabepilone in combination with cyclophosphamide for the neoadjuvant treatment of locally advanced breast cancer. In this regimen, ixabepilone is substituted for docetaxel, since preclinical and clinical

studies suggest that ixabepilone is more active than either docetaxel or paclitaxel. The combination of ixabepilone and cyclophosphamide could further improve the efficacy of non-anthracycline neoadjuvant therapy.

In this study, patients with early stage, HER2-negative breast cancer will receive neoadjuvant treatment with ixabepilone and cyclophosphamide given every three weeks for a total of six cycles. Following surgery patients with hormone receptor-positive tumors will receive anti-estrogen treatment. Patients may receive local regional radiation therapy after surgery per institutional guidelines at the investigator's discretion. Baseline tumor tissue and tumor tissue removed at the time of surgery will be tested by Oncotype Detailed Description (DX) assay to determine whether it is predictive of response to this neoadjuvant treatment regimen. This study will be one of the first investigations of the combination of ixabepilone and cyclophosphamide as neoadjuvant treatment for HER2-negative breast cancer. It will examine this treatment regimen for potential advantages gained from substitution of ixabepilone for a taxane and use of non-anthracycline agents.

Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER-2 Negative Breast Cancer

Phase II Study of Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER2-Negative Breast Cancer

Pathologic complete response (pCR) rate will be determined by the pathologic evaluation of breast and lymph node samples collected at the time of surgery. pCR is defined as no residual disease in breast or lymph nodes in resected tissue samples.

Non hematologic treatment-related grade 4 toxicities measured according to CTCAE 3.0

Overall survival (OS) determined as the time between day 1 cycle 1 to the date of death from any cause. The percentage of patients who were alive at 3 years, estimated by Kaplan Meier method as the probability of being event free at 3 years is reported here.

Defined as the time between Day 1 Cycle 1, and date of first documented recurrence, initiation of additional chemotherapy, or death.

All patients who received a dose of study treatment

Ixabepilone/Cyclophosphamide

All patients who received at least one dose of treatment.

Arm/Group 1

To be evaluable, patients had to undergo surgery after neoadjuvant therapy. Out of 168 patients, only 161 patients underwent surgery after neoadjuvant therapy and were included in this analysis.

Pathologic Complete Response Rate (pCR)

Peripheral neuropathy

Absence of Grade-4 Non-hematologic Toxicity Excluding, Alopecia, Nausea, Vomiting and Bone Pain

Systemic Therapy followed by surgery and possible radiation therapy

Ixabepilone: 40 mg/m2 IV infusion over 3 hours on day 1 of a 21 day cycle for 6 cycles

Cyclophosphamide: 600 mg/m2 IV infusion per institutional guidelines on day 1 of a 21 day cycle for 6 cycles

All patients who received a dose of study treatment.

Overall Survival

Ixabepilone: 40 mg/m2 via intraveous (IV) infusion over 3 hours

Cyclophosphamide: 600 mg/m2 via IV infusion per institutional guidelines

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ixabepilone to Treat Cervical Cancer	NCT00924066	Cervical Carcin... Cervical Adenoc... Cervical Adenos... Cervical Carcin...	Ixempra (Ixabep...	18 Years - 80 Years	National Institutes of Health Clinical Center (CC)
Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer	NCT00825734	Metastatic Brea...	Sorafenib Ixabepilone	18 Years -	SCRI Development Innovations, LLC
Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER-2 Negative Breast Cancer	NCT00866905	Breast Cancer	Ixabepilone Cyclophosphamid...	18 Years -	SCRI Development Innovations, LLC

Spots Global Cancer Trial Database for ixempra

Every month we try and update this database with for ixempra cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ixempra

Every month we try and update this database with for ixempra cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ixempra cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.