- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00103259
Bortezomib With or Without Irinotecan in Treating Patients With Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Phase II Two Arm Trial of the Proteasome Inhibitor, PS-341 (Velcade TM) in Combination With Irinotecan or PS-341 Alone Followed by the Addition of Irinotecan at Time of Progression in Patients With Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Study Overview
Status
Conditions
- Tongue 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
- Recurrent Squamous Cell Carcinoma of the Nasopharynx
- Stage IV Squamous Cell Carcinoma of the Hypopharynx
- Stage IV Squamous Cell Carcinoma of the Larynx
- Stage IV Squamous Cell Carcinoma of the Nasopharynx
- Stage IV Verrucous Carcinoma of the Larynx
- 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 Oral Cavity
- 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 Oral Cavity
- 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 Oral Cavity
- Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the activity of combination of PS-341 (bortezomib) and irinotecan in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) and the response rate of single agent PS-341 (followed by irinotecan at time of progression).
SECONDARY OBJECTIVES:
I. To continue exploring the toxicity of PS-341 alone and the combination of PS-341 and irinotecan in this patient population.
II. To evaluate time to progression, overall survival and response to irinotecan and PS-341 when given after PS-341 alone.
III. To evaluate the relationship between pre-treatment nuclear localization of NF-kB, and NF-kB regulated gene expression in tissue (Cyclin D1, IAP1, Bcl-XL, Topo I), and serum (IL-6, IL-8, GRO-1 and VEGF) and response.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV over 90 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive bortezomib as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients may cross over to arm I.
Patients are followed every 3-6 months for up to 3 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Eastern Cooperative Oncology Group
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients may have had one (0-1) prior chemotherapy regimen for recurrent or metastatic SCCHN; chemotherapy for recurrent or metastatic disease must have been completed at least 4 weeks prior to study entry
Patients must not have been previously treated with irinotecan or bortezomib
- Patients must not be receiving radiation treatment
- Patients must have histologically confirmed squamous cell carcinoma of the head and neck
Patients must have biopsy for histological confirmation of recurrent or metastatic disease if disease is now recurrent or metastatic after prior disease free-interval
- NOTE: If patient has had a complete response (of any duration) but now has suspected recurrent disease (regardless of the time interval), the patient will need a biopsy for confirmation of SCCHN
- Disease must not be amenable to potentially curative local therapies or patient must have refused such options
- Patients must not have nasopharyngeal subtypes WHO II or III. Patients may have nasopharyngeal WHO I; salivary gland primaries are excluded from study SUBTYPES OF NASOPHARYNGEAL CARCINOMA (NPC) WHO type 1 - keratinizing SCC WHO type 2 - nonkeratinizing epidermoid carcinoma WHO type 3 - undifferentiated carcinoma
Patients must have measurable disease
- Baseline measurements and evaluations must be obtained within 4 weeks of registration to the study
- Measurable disease limited to a pre-irradiated location must be biopsy proven to be squamous cell carcinoma
Must have at least one objective measurable disease parameter; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; all areas of disease should be recorded and mapped out in order to assess response and uniformity of response to therapy
- Radiographic findings are acceptable providing that clear-cut measurement can be made
- Measurable disease limited to a pre-irradiated location must be biopsy-proven to be squamous cell carcinoma
- Patients must have ECOG performance status 0 or 1
- Patients must not have grade 2 or higher peripheral neuropathy within 2 weeks of study entry
- Leukocytes >= 3,000/uL
- Absolute neutrophil count >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin within normal institutional limits
- AST(SGOT) and ALT(SGPT) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR
- Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Patients must have had no prior invasive malignancy unless the disease-free interval is 5 years or more
- Women must not be pregnant or breast-feeding due to the fact that the teratogenic or abortifacient effects of PS-341are unknown; the effect of PS-341 on the nursing infant are also unknown; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients must not have history of allergic reactions to PS-341 or allergic reaction attributed to compounds of similar chemical or biologic composition to PS-341 including boron or mannitol
- Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
ELIGIBILITY FOR RE-REGISTRATION TO ARM A (FOR ARM B PATIENTS AT THE TIME OF PROGRESSION
- Patients must have ECOG performance status 0 or 1
- Leukocytes >= 3,000/uL
- Absolute neutrophil count >- 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin within normal institutional limits
- AST(SGOT) and ALT(SGPT) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (bortezomib, irinotecan hydrochloride)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV over 90 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity
|
Optional correlative studies
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Arm II (bortezomib)
Patients receive bortezomib as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Upon disease progression, patients may cross over to arm I.
|
Optional correlative studies
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response Rate on Step 1
Time Frame: Tumor response was assessed every 2 cycles until progression or intolerable toxicity with maximum of 3 years
|
Tumor response was evaluated via Response Evaluation Criteria In Solid Tumors (RECIST) v1.0, and response rate was defined as the proportion of patients with a complete response or partial response among all eligible and treated patients.
Complete response was defined as disappearance of all tumor lesions.
Partial response was defined as at least a 30% decrease in the sum of the longest diameters of target lesions.
|
Tumor response was assessed every 2 cycles until progression or intolerable toxicity with maximum of 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response Rate on Step 2
Time Frame: Tumor response was assessed after every 2 cycles until progression or intolerable toxicity with maximum of 3 years
|
Tumor response was evaluated via Response Evaluation Criteria In Solid Tumors (RECIST) v1.0, and response rate was defined as the proportion of patients with a complete response or partial response among all eligible and treated patients.
Complete response was defined as disappearance of all tumor lesions.
Partial response was defined as at least a 30% decrease in the sum of the longest diameters of target lesions.
|
Tumor response was assessed after every 2 cycles until progression or intolerable toxicity with maximum of 3 years
|
Progression-free Survival on Step 1
Time Frame: Every 3 months for first 2 years from protocol entry, then every 6 months until 3 years from study entry
|
Progression-free survival was defined as time from registration to step 1 to disease recurrence or death from any cause, whichever occurred first.
Disease progression was measured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions.
|
Every 3 months for first 2 years from protocol entry, then every 6 months until 3 years from study entry
|
Overall Survival on Step 1
Time Frame: Survival was assessed every 3 month within 2 years and every 6 months betwen 2 and 3 years
|
Overall survival was defined as time from registration on step 1 to death from any cause.
It was evaluated in all 61 eligible and treated patients.
|
Survival was assessed every 3 month within 2 years and every 6 months betwen 2 and 3 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jill Gilbert, Eastern Cooperative Oncology Group
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Respiratory Tract Neoplasms
- Pharyngeal Neoplasms
- Otorhinolaryngologic Neoplasms
- Head and Neck Neoplasms
- Nasopharyngeal Diseases
- Pharyngeal Diseases
- Stomatognathic Diseases
- Otorhinolaryngologic Diseases
- Mouth Diseases
- Paranasal Sinus Diseases
- Nose Diseases
- Neoplasms, Squamous Cell
- Nasopharyngeal Neoplasms
- Mouth Neoplasms
- Tongue Diseases
- Nose Neoplasms
- Carcinoma
- Nasopharyngeal Carcinoma
- Recurrence
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Oropharyngeal Neoplasms
- Laryngeal Neoplasms
- Laryngeal Diseases
- Carcinoma, Verrucous
- Tongue Neoplasms
- Paranasal Sinus Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Irinotecan
- Bortezomib
Other Study ID Numbers
- NCI-2012-02953 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA021115 (U.S. NIH Grant/Contract)
- E1304 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Tongue Cancer
-
Indiana UniversityWithdrawnTongue Cancer | Tongue TumorUnited States
-
Fuda Cancer Hospital, GuangzhouShenzhen Hank Bioengineering InstituteCompletedRecurrent Tongue CancerChina
-
Samsung Medical CenterNational Cancer Center, Korea; Asan Medical Center; Seoul National University... and other collaboratorsRecruitingSurgery | Tongue Cancer | Squamous Cell Carcinoma | Resection Margin | Tongue Cancer TNM Staging Primary Tumor (T) T1 | Tongue Cancer TNM Staging Primary Tumor (T) T2Korea, Republic of
-
University of MichiganRecruitingOral Cancer | Tongue Cancer | Tongue NeoplasmsUnited States
-
tiejun ZhangUnknown
-
Oslo University HospitalOslo Metropolitan UniversityCompleted
-
National Taiwan University HospitalNot yet recruiting
-
Centre Hospitalier Universitaire DijonCompleted
-
Tata Memorial HospitalNATIONAL CANCER GRIDRecruitingCancer of the Head and Neck | Cancer of Mouth | Cancer of the Tongue | Buccal Mucosa Cancer | Floor of Mouth CarcinomaIndia
-
Sunnybrook Health Sciences CentreUniversity of Toronto; Sunnybrook Research InstituteRecruiting
Clinical Trials on laboratory biomarker analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed