Ixabepilone in Treating Patients With Metastatic or Recurrent Squamous Cell Cancer of the Head and Neck

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00033618
First received: April 9, 2002
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

Randomized phase II trial to study the effectiveness of ixabepilone in treating patients who have metastatic or recurrent head and neck cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die


Condition Intervention Phase
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Salivary Gland Squamous Cell Carcinoma
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IVA Salivary Gland Cancer
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Salivary Gland Cancer
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Stage IVC Salivary Gland Cancer
Stage IVC Squamous Cell Carcinoma of the Larynx
Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVC Squamous Cell Carcinoma of the Oropharynx
Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVC Verrucous Carcinoma of the Larynx
Stage IVC Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Drug: ixabepilone
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of BMS-247550 (NSC #710428) Given Daily x 5 Days Every 3 Weeks or Weekly in Patients With Metastatic or Recurrent Squamous Cell Cancer of the Head and Neck

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate, assessed using RECIST criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    95% confidence interval will be computed.


Secondary Outcome Measures:
  • Time to progression [ Time Frame: From the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Grade 3 of 4 hematologic toxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 144
Study Start Date: November 2002
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (ixabepilone)
Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (ixabepilone)
Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the response rate and toxicity of BMS-247550 given in two dosing schedules in taxane-naïve and taxane-exposed patients.

II. To provide information about the response rate and toxicity of BMS-247550 given in two dosing schedules.

SECONDARY OBJECTIVES:

I. To measure surviving expression and correlate with the therapeutic responsiveness to BMS-247550.

II. To determine the changes in tumor vascular density and endothelial cell apoptosis in response to therapy and the correlation of these changes to outcome.

OUTLINE: This is a randomized study. Patients are stratified according to prior taxane therapy (yes vs no) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm II: Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

In both arms, patients achieving complete response (CR) receive 2 additional courses past CR if a minimum of 6 courses have been administered.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have measurable histologically confirmed squamous cell carcinoma of the head and neck, excluding nasopharyngeal primaries, that is incurable with surgery or radiation therapy; disease must be measurable as defined by RECIST =< 4 weeks of randomization

    • Patients must have distant metastases or locoregional recurrence or persistent disease within a radiation portal
    • Baseline tumor measurements/evaluations must be obtained < 4 weeks prior to randomization
  • Patients may have received up to one prior biotherapy regimen and treatment must have been completed at least 4 weeks prior to randomization; no more than two prior chemotherapy regimens for recurrent and/or metastatic disease are permitted; patients may have received prior docetaxel or paclitaxel, but must not have been previously treated with an investigational taxane; chemotherapy treatment must have been completed at least 4 weeks prior to randomization
  • If the only site of measurable disease is a previously irradiated area, the patient must have documented progressive disease or biopsy-proven residual carcinoma; persistent disease after radiotherapy must be biopsy-proven at least 8 weeks after the completion of radiotherapy; patients must have completed radiotherapy at least 4 weeks prior to randomization
  • Patients must not have a concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; patients with prior malignancies who have been disease-free > 2 years are eligible
  • Patients must have ECOG performance status of 0 or 1
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Serum creatinine =< 1.2 mg OR creatinine clearance >= 50 ml/min NOTE: Either calculated or actual creatinine clearance can be used NOTE: The creatinine clearance may be calculated by the Cockcroft-Gault formula
  • Total bilirubin =< 1.5 mg
  • (SGOT) AST, (SGPT) ALT =< 2 x institutional upper limit of normal
  • Alkaline phosphatase =< 2 x institutional upper limit of normal
  • Serum calcium within institutional normal range and no history of malignancy associated hypercalcemia
  • Patients must not have a pre-existing peripheral neuropathy >= grade 2
  • Patients must not have an active infection nor currently be receiving treatment for a recent infection
  • Patients must have recovered from the effects of any recent surgery
  • Female patients must not be pregnant or breastfeeding; the effects of BMS-247550 on pregnant women and on fetuses are unknown; however, the known toxicities, which include neutropenia, are likely to place pregnant women at increased risk; the mechanism of action of this compound, stabilization of microtubules in dividing cells, is highly likely to be teratogenic; taxanes, which have a similar mechanism of action, are known to be teratogenic NOTE: A negative serum pregnancy test is required =< 2 weeks of randomization for women of childbearing potential
  • Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception
  • Patients must not have a known hypersensitivity to castor oil, or agents containing Cremophor El, or paclitaxel; patients with a history of grade 1 or uncomplicated, non-recurrent grade 2 hypersensitivity reactions associated with Cremophor will be eligible with prophylaxis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00033618

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Barbara Burtness Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00033618     History of Changes
Other Study ID Numbers: NCI-2012-02970, E2301, U10CA021115, CDR0000069305
Study First Received: April 9, 2002
Last Updated: February 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Nose Neoplasms
Carcinoma, Squamous Cell
Paranasal Sinus Neoplasms
Salivary Gland Neoplasms
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Carcinoma, Verrucous
Laryngeal Diseases
Laryngeal Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Unknown Primary
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Otorhinolaryngologic Neoplasms
Neoplasms by Site
Nose Diseases
Respiratory Tract Diseases
Paranasal Sinus Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases
Pharyngeal Neoplasms
Pharyngeal Diseases
Neoplasm Metastasis
Neoplastic Processes

ClinicalTrials.gov processed this record on September 16, 2014