Bortezomib With or Without Irinotecan in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00103259
First received: February 7, 2005
Last updated: January 2, 2013
Last verified: January 2013
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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 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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) |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Response Rate on Step 1 [ Time Frame: Tumor response was assessed every 2 cycles until progression or intolerable toxicity with maximum of 3 years ] [ Designated as safety issue: No ]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.
Secondary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]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.
| Enrollment: | 71 |
| Study Start Date: | July 2005 |
| Study Completion Date: | August 2012 |
| Primary Completion Date: | January 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (bortezomib+irinotecan)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan hydrochloride 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
PS-341 1.3 mg/m2 IV push over 3-5 seconds twice weekly on days 1, 4, 8 and 11 followed by one week of rest q 21 days
Other Name: VelcadeTM, MLN-341, LDP-341, PS-341
Drug: irinotecan hydrochloride
Irinotecan 90 mg/m2 IV over 90 minutes one hour after PS-341 given on days 1 and 8, q 21 days
Other Name: Camptosar, CPT-11
|
|
Experimental: Arm II (bortezomib)
Patients receive bortezomib (PS-341) 1.3 mg/m2 IV over 3-5 seconds twice weekly on days 1, 4, 8 and 11 followed by one week of rest. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients may cross over to arm I (bortezomib + irinotecan).
|
Drug: bortezomib
PS-341 1.3 mg/m2 IV push over 3-5 seconds twice weekly on days 1, 4, 8 and 11 followed by one week of rest q 21 days
Other Name: VelcadeTM, MLN-341, LDP-341, PS-341
|
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 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00103259
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Investigators
| Study Chair: | Jill Gilbert, MD | MBCCOP - LSU Health Sciences Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00103259 History of Changes |
| Obsolete Identifiers: | NCT00695721 |
| Other Study ID Numbers: | NCI-2012-02953, U10CA021115, E1304, CDR0000409577 |
| Study First Received: | February 7, 2005 |
| Results First Received: | November 24, 2012 |
| Last Updated: | January 2, 2013 |
| 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 |
Additional relevant MeSH terms:
|
Carcinoma, Squamous Cell Head and Neck Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell Neoplasms by Site Irinotecan Camptothecin Bortezomib |
Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Protease Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013