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)
18 Years
N/A
Both
Head and Neck Cancer
Trial Information
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)
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 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 nuclear factor
kappa-light-chain-enhancer of activated B cells (NF-kB), and NF-kB-regulated gene
expression in tissue (Cyclin D1, Inhibitor of Apoptosis Protein 1 (IAP1), B-cell
lymphoma-extra large (Bcl-XL), and Topoisomerase (Topo) I), and serum (Interleukin 6
(IL-6), IL-8, Growth-regulated oncogene-1 (GRO-1), and Vascular endothelial growth
factor (VEGF)) and response.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1). Patients are
randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bortezomib intravenously (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.
Actual Accrual: A total of 71 patients have been enrolled onto the study.
Inclusion Criteria
Inclusion criteria:
- 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 computed tomography (CT) scan
- Biopsy confirmation required for target lesions limited to an irradiated
location
- 18 and over
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Whole Blood Cell (WBC) ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) test measures the
amount of this enzyme in the blood. ALT is found mainly (ALT) ≤ 2.5 times upper limit
of normal
- Creatinine normal OR Creatinine clearance ≥ 60 mL/min
- Negative pregnancy test
- Fertile patients must use effective contraception
Exclusion criteria:
- World Health Organization (WHO) type II or III nasopharyngeal cancer
- Primary salivary gland cancer
- Known brain metastases
- Pregnant or nursing
- Unstable angina pectoris
- Peripheral neuropathy ≥ grade 2 within the past 2 weeks
- Other invasive malignancy within the past 5 years
- History of allergic reaction to bortezomib
- History of allergic reaction attributed to compounds of similar chemical or
- Ongoing or active infection
- Psychiatric illness or social situation that would preclude study compliance
- Other uncontrolled illness
- Less than 4 weeks since prior chemotherapy for recurrent or metastatic disease
- More than 1 prior chemotherapy regimen for recurrent or metastatic squamous cell
carcinoma of the head and neck
- Prior irinotecan
- Prior bortezomib
- Concurrent radiotherapy
- Concurrent cyclosporine
- Concurrent antiepileptics
- Other concurrent investigational agents
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response Rate on Step 1
Outcome Description:
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.
Outcome Time Frame:
Tumor response was assessed every 2 cycles until progression or intolerable toxicity with maximum of 3 years
Safety Issue:
No
Principal Investigator
Jill Gilbert, MD
Investigator Role:
Study Chair
Investigator Affiliation:
MBCCOP - LSU Health Sciences Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02953
NCT ID:
NCT00103259
Start Date:
July 2005
Completion Date:
August 2012
Related Keywords:
- Head and Neck Cancer
- 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
- Carcinoma, Squamous Cell
- Head and Neck Neoplasms
Name | Location |
|---|---|
| CCOP - Carle Cancer Center | Urbana, Illinois 61801 |
| CCOP - Iowa Oncology Research Association | Des Moines, Iowa 50309-1016 |
| Rush-Copley Cancer Care Center | Aurora, Illinois 60507 |
| Joliet Oncology-Hematology Associates, Limited - West | Joliet, Illinois 60435 |
| Carle Cancer Center at Carle Foundation Hospital | Urbana, Illinois 61801 |
| Saint Anthony Memorial Health Centers | Michigan City, Indiana 46360 |
| Mercy Medical Center - Sioux City | Sioux City, Iowa 51104 |
| Siouxland Hematology-Oncology Associates, LLP | Sioux City, Iowa 51101 |
| St. Luke's Regional Medical Center | Sioux City, Iowa 51104 |
| Bronson Methodist Hospital | Kalamazoo, Michigan 49007 |
| West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
| Borgess Medical Center | Kalamazooaa, Michigan 49001 |
| Mercy Cancer Center at Mercy Medical Center | Canton, Ohio 44708 |
| St. Rita's Medical Center | Lima, Ohio 45801 |
| Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
| Medical X-Ray Center, PC | Sioux Falls, South Dakota 57105 |
| Avera Cancer Institute | Sioux Falls, South Dakota 57105 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
| Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center | La Crosse, Wisconsin 54601 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
| Marshfield Clinic - Indianhead Center | Rice Lake, Wisconsin 54868 |
| Kimmel Cancer Center at Thomas Jefferson University - Philadelphia | Philadelphia, Pennsylvania 19107 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| John Stoddard Cancer Center at Iowa Methodist Medical Center | Des Moines, Iowa 50309 |
| Albert Einstein Cancer Center at Albert Einstein College of Medicine | Bronx, New York 10461 |
| St. Vincent Hospital Regional Cancer Center | Green Bay, Wisconsin 54307-3508 |
| Green Bay Oncology, Limited - Escanaba | Escanaba, Michigan 49431 |
| Dickinson County Healthcare System | Iron Mountain, Michigan 49801 |
| Our Lady of Mercy Medical Center Comprehensive Cancer Center | Bronx, New York 10466 |
| St. Mary's Hospital Medical Center - Green Bay | Green Bay, Wisconsin 54303 |
| Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center | Green Bay, Wisconsin 54301-3526 |
| Green Bay Oncology, Limited at St. Mary's Hospital | Green Bay, Wisconsin 54303 |
| Bay Area Cancer Care Center at Bay Area Medical Center | Marinette, Wisconsin 54143 |
| Green Bay Oncology, Limited - Oconto Falls | Oconto Falls, Wisconsin 54154 |
| Green Bay Oncology, Limited - Sturgeon Bay | Sturgeon Bay, Wisconsin 54235 |
| University of Illinois Cancer Center | Chicago, Illinois 60612-7243 |
| Swedish-American Regional Cancer Center | Rockford, Illinois 61104-2315 |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey 08903 |
| Decatur Memorial Hospital Cancer Care Institute | Decatur, Illinois 62526 |
| Fox Chase Cancer Center - Philadelphia | Philadelphia, Pennsylvania 19111-2497 |
| Veterans Affairs Medical Center - Chicago Westside Hospital | Chicago, Illinois 60612 |
| UPMC Cancer Centers | Pittsburgh, Pennsylvania 15232 |
| John Stoddard Cancer Center at Iowa Lutheran Hospital | Des Moines, Iowa 50316-2301 |
| Mercy Capitol Hospital | Des Moines, Iowa 50307 |
| Medical Oncology and Hematology Associates at John Stoddard Cancer Center | Des Moines, Iowa 50309 |
| Medical Oncology and Hematology Associates at Mercy Cancer Center | Des Moines, Iowa 50314 |
| Mercy Cancer Center at Mercy Medical Center - Des Moines | Des Moines, Iowa 50314 |
| Greater Baltimore Medical Center Cancer Center | Baltimore, Maryland 21204 |
| Summa Center for Cancer Care at Akron City Hospital | Akron, Ohio 44309-2090 |
| St. Luke's Cancer Network at St. Luke's Hospital | Bethlehem, Pennsylvania 18015 |
| Center for Cancer Treatment & Prevention at Sacred Heart Hospital | Eau Claire, Wisconsin 54701 |
| Marshfield Clinic Cancer Care at Regional Cancer Center | Eau Claire, Wisconsin 54701 |
| Saint Joseph's Hospital | Marshfield, Wisconsin 54449 |
| Marshfield Clinic - Lakeland Center | Minocqua, Wisconsin 54548 |
| Ministry Medical Group at Saint Mary's Hospital | Rhinelander, Wisconsin 54501 |
| Saint Michael's Hospital Cancer Center | Stevens Point, Wisconsin 54481 |
| Marshfield Clinic - Wausau Center | Wausau, Wisconsin 54401 |
| Marshfield Clinic - Weston Center | Weston, Wisconsin 54476 |
| Marshfield Clinic - Wisconsin Rapids Center | Wisconsin Rapids, Wisconsin 54494 |
| Regional Cancer Center at Memorial Medical Center | Springfield, Illinois 62781-0001 |
