Bortezomib With or Without Irinotecan in Treating Patients With Recurrent or Metastatic Head and Neck Cancer - Full Text View

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00103259

Purpose

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with irinotecan may kill more tumor cells. It is not yet known whether giving bortezomib together with irinotecan is more effective than bortezomib alone in treating head and neck cancer.

PURPOSE: This randomized phase II trial is studying bortezomib and irinotecan to see how well they work compared to bortezomib alone in treating patients with recurrent or metastatic head and neck cancer.

Condition	Intervention	Phase
Head and Neck Cancer	Drug: bortezomib Drug: irinotecan hydrochloride	Phase II

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Irinotecan U 101440E Irinotecan hydrochloride Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Phase II Two Arm Trial of the Proteasome Inhibitor, PS-341 (Velcade™) 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)

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

Primary Outcome Measures:

Response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Activity of bortezomib [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	102
Study Start Date:	July 2005
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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.	Drug: bortezomib Given IV Drug: irinotecan hydrochloride Given IV
Arm II: Experimental 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.	Drug: bortezomib Given IV

Detailed Description:

OBJECTIVES:

Primary

Compare the activity of bortezomib in combination with irinotecan vs bortezomib alone in patients with locally recurrent or metastatic squamous cell carcinoma of the head and neck.
Determine the response rate in patients treated with single-agent bortezomib followed by bortezomib in combination with irinotecan at time of disease progression.

Secondary

Compare the toxicity of these regimens in these patients.
Compare time to progression, overall survival, and response in patients treated with these regimens.
Evaluate the relationship between pre-treatment nuclear localization of NF-kB, and NF-kB-regulated gene expression in tissue (Cyclin D1, IAP1, Bcl-XL, and Topo I), and serum (IL-6, IL-8, GRO-1, and VEGF) and response.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1). 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.

PROJECTED ACCRUAL: A total of 39-102 patients (26-61 for arm I and 13-41 for arm II) will be accrued for this study within 6.5-17 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed squamous cell carcinoma of the head and neck
- Locally recurrent or metastatic disease
  - Recurrent or metastatic disease must be confirmed by biopsy after prior disease-free interval
Not amenable to potentially curative local therapies OR patient has refused local therapies
Measurable disease
- At least 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan
- Biopsy confirmation required for target lesions limited to an irradiated location
No WHO type II or III nasopharyngeal cancer
No primary salivary gland cancer
No known brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal

Renal

Creatinine normal OR
Creatinine clearance ≥ 60 mL/min

Cardiovascular

No unstable angina pectoris

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No peripheral neuropathy ≥ grade 2 within the past 2 weeks
No other invasive malignancy within the past 5 years
No history of allergic reaction to bortezomib
No history of allergic reaction attributed to compounds of similar chemical or biologic composition to bortezomib, including boron or mannitol
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

At least 4 weeks since prior chemotherapy for recurrent or metastatic disease
No more than 1 prior chemotherapy regimen for recurrent or metastatic squamous cell carcinoma of the head and neck
No prior irinotecan

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics
No concurrent radiotherapy

Surgery

Not specified

Other

No prior bortezomib
No concurrent cyclosporine
No concurrent antiepileptics
No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103259

Show 60 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Jill Gilbert, MD	MBCCOP - LSU Health Sciences Center
Investigator:	Athanassios Argiris, MD	UPMC Cancer Centers

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000409577, ECOG-E1304
Study First Received:	February 7, 2005
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00103259 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the oropharynx
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 metastatic squamous neck cancer with occult primary
recurrent squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
untreated metastatic squamous neck cancer with occult primary

Study placed in the following topic categories:

Nasopharyngeal Carcinoma
Laryngeal Carcinoma
Bortezomib
Irinotecan
Disease Progression
Carcinoma, Squamous Cell of Head and Neck
Squamous Cell Carcinoma
Camptothecin
Recurrence
Protease Inhibitors

Hypopharyngeal Cancer
Carcinoma
Metastatic Squamous Neck Cancer With Occult Primary
Head and Neck Neoplasms
Epidermoid Carcinoma
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Irinotecan
Bortezomib
Enzyme Inhibitors
Pharmacologic Actions
Camptothecin
Protease Inhibitors

Carcinoma
Neoplasms
Neoplasms by Site
Therapeutic Uses
Head and Neck Neoplasms
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009