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A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Clinical Trials Information presented on Clinical Trials Search isn't intended to be a substitute for proven healthcare advice, trips or treatment using a real physician. We are not docs. Always confer with your mD on A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck conditions. Clinical Trials Search.org is a site dedicated to listing clinical research studies in human subjects. A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Clinical research trials and A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck medical trials take place in hundreds of localities across the U.S.. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials usually measure the effectiveness of new drugs. The intention of the studies / projects is to resolve certain human health questions. Clinical trials are a popular means for physicians, government agencies, and private sector corporations to detect remedies for all forms of circumstances, like A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck. A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Clinical Trials and other clinical trials allow for volunteers to undergo healthcare treatment options before they are available to the masses. Most times the participants receive treatment for free, and every now and again they are paid for their time. Occasionally there is a cost for a A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck clinical trial. Subjects typically recieve the finest healthcare available for their A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck condition. Hazards are a reality, nonetheless, and might include more or frequent mD trips, health risks (potentially life-endangering), and/or the treatment being ineffective. Trials are federally regulated with stern guidelines to protect clinical trials subjects.
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Home > "A" Clinical Trials Conditions > A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck  A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
For Condition: Squamous Cell Carcinoma
Status: Recruiting
Sponsor(s): National Cancer Institute (NCI) ,
Synopsis: Squamous cell carcinomas of the head and neck (SSCHN) account for 4 percent of all cancers. Most are initially treated with surgery, radiation, or both. For those patients whose cancer has spread and is not treatable by surgery, radiation and chemotherapy are often combined. These current treatments may help control growth but do not offer a chance for a cure. This study will investigate the effects of a new investigational chemotherapy drug, PS-341, on both the cancer and the patient when it is administered twice a week at the same time as radiation therapy. This drug has been shown to slow down or stop the growth of cancer cells in culture and in mice. In addition, when the cells are treated with the drug and radiation, the killing effect of the radiation seems to be increased. Eligible participants are patients over 18 years old with confirmed SCCHN which is persistent or recurrent and inoperable; with distant metastases following standard treatment; or with local disease that can be treated by radiation. Scans such as CT and MRI will be done to determine the extent of the cancer; an EKG, blood work, pregnancy test, and HIV test will also be done. An examination will be done under anesthesia during which a small piece of the tumor will be removed for diagnosis and research. Patients will be divided into two groups: those who had radiation therapy more than 6 months ago and those who had no radiation therapy but who had surgery or chemotherapy more than 4 weeks ago. PS-341 will be administered every Monday and Thursday for as long as radiation lasts: 7 weeks for retreatment cases or 8 weeks for primary treatment. The first radiation treatment will be given 24 hours after the first dose of PS-341 and will continue to be given once a day, Monday through Friday. A biopsy may be requested on the Tuesday and Wednesday following the first dose of PS-341. Before and after each injection, a blood sample will be taken. In addition, patients will be seen once a week in the clinic, where a history and physical exam will be done and another blood sample taken. Twelve weeks after radiation is completed, and every few months thereafter, an X-ray or MRI scan will be done to determine the extent of the cancer. Patients will also be seen every month for the first year after radiation to monitor for and treat any adverse effects. Blood will be collected at each visit. Dosage will be increased for each group of patients as long as there are no severe side effects. PS-341 has certain known side effects, such as nausea, vomiting, loss of appetite, decreased blood pressure, lightheadedness, fast heart rate, and decreases in white blood cells and platelets. It has not been found to cause any deaths in humans in studies thus far. However, it is an investigational drug and has not yet been given to large numbers of patients or followed up for long periods.
Details: The ubiquitin-proteasome pathway regulates the degradation of important regulatory proteins and transcription factors that control the cell cycle and cell death. Proteasome inhibition can lead to block of different phases of the cell cycle, and block expression of genes that prevent cell death induced by radiation or other cytotoxic therapeutic agents. In preclinical studies, proteasome inhibitor PS-341 has demonstrated cytotoxic, radiosensitizing, and anti-tumor activity against squamous cell carcinomas of the head and neck (SCCHN). The primary objective of this phase I dose escalation clinical study is to determine the maximum tolerated dose of PS-341 to be given concomitant with radiation in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This dose will correspond to the dose that causes greater than Grade 3 mucosal, skin, or hematologic toxicity in less than or equal to 1 of 6 patients or which causes greater than or equal to Grade 3 other toxicity in less than or equal to 1 of 6 patients, with the exception that hyptension with or without hyponatremia will be supported with saline infusions when serum Na is less than 130 mEq/L but greater than 125 mEq/, and BP responding to less than or equal to 2.5 Liters over up to 24 hours will not be dose-limiting. Secondary objectives include detection of 20S proteasome inhibition, cell cycle block, apoptosis and inhibition of transcription factor NF-kB activation in tumor tissue biopsies following PS-341 and radiation. Eligible patients include those with persistent or recurrent SCCHN who are candidates for local primary or re-irradiation, ECOG performance less than or equal to 2, life expectancy greater than 3 months, adequate organ function (PLT greater than 100,000/ microliter, neutrophils greater than 1500/microliter, serum creatinine less than 1.5 x upper limits normal (ULN), serum bilirubin less than 1.5 x ULN, serum transaminases less than 2.5 x ULN) and absence of unstable infection or other medical conditions. Patients may not have had systemic chemotherapy within the past 4 weeks and must have recovered from chemotherapy toxicity. Patients must be greater than 6 months since prior radiation. PS-341 will be given in escalating doses in cohorts of 3 or more patients by IV bolus on M, Th, and radiation will be given in 1.8 Gy fractions M-F to 60 Gy in previously radiated or 72Gy in previously unirradiated patients. Radiation and drug will be given in two courses each delivering 50% of the prescribed doses split by a two-week rest to allow recovery from or attenuation of combined modality. Inhibition of 20S proteasome activity in blood by PS-341 will be monitored before and 1hour post infusion M, Th.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA Patients must meet the following inclusion criteria: Patients with histologically confirmed SCCHN which is persistent or recurrent and unresectable; or patients presenting with or developing distant metastases following standard curative measures, and who have local regional disease amenable to radiation or re-irradiation therapy are eligible. Patients with a history of treatment for other prior malignancy will be eligible, provided they remain disease-free more than 2 years after initial treatment, or were treated for non-melanoma skin cancer, or in situ cervical cancer. Because of greater potential for acute toxicity in previously irradiated patients, patients will be stratified based on whether they have received prior radiation. Stratum A: Prior radiation therapy (greater than 6 months) with or without prior surgery or chemotherapy. Stratum B: No prior radiation therapy, but greater than or equal to 4 weeks after surgery or chemotherapy. Age greater than 18 years of age. ECOG performance status less than or equal to 2 (Karnofsky greater than 50%). Life expectancy greater than 3 months. Patients must have adequate organ and marrow function as defined below: absolute neutrophil count greater than 1,500/microliter platelets greater than 100,000/microliter total bilirubin less than 1.5 X ULN AST(SGOT)/ALT(SGPT) less than 2.5 X ULN serum creatinine less than 1.5 X ULN or creatinine clearance greater than 60 mL/min/1.73 m(2) for patients with creatinine levels equal to or greater than 1.5 X ULN. Men and women of child-bearing potential must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or a participating spouse are enrolled in this study, she should inform her treating physician immediately. Because the potential risk of toxicity in nursing infants secondary to PS-341 treatment of the mother is unknown but may be harmful, breastfeeding should be discontinued if the mother is treated with PS-341. Ability to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: Patients who have had surgery, chemotherapy, or immunotherapy within 4 weeks, or radiotherapy within 6 months prior to entering the study. Patients undergoing therapy with other investigational agents. Patients with known brain metastases should 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 toxicities. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the past 6 months, unstable angina pectoris, or unstable cardiac arrhythmia requiring assessment for clinical intervention. Pregnant and nursing women are excluded from this study because PS-341 is an investigational agent with unknown effects on the fetus and nursing infant. HIV-positive patients are excluded from the study because of possible pharmacokinetic interactions with medication necessary to control HIV or its complication and owing to uncertain interaction of PS-341 with immune function. Patients with postural hypotentsion due to severe baroreceptor dysfunction after previous radiation and/or surgery defined as a) postural hypotension that cannot be corrected with volume repetion to systolic blood pressure greater than 100 mm Hg and absence of orthostatic changes or symptoms; b) postural hypotension that cannot be corrected with volume repletion to systolic blood pressure greater than 120 mm Hg with orthostatic changes and asence of symptoms. Patients with hyponatremia not correctable to greater than or equal to 130 mEq/L will be excluded.
Total Enrollment: 51
Location and Contact Information:
National Cancer Institute (NCI) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Clinical Support Center/NCI 1-888-624-1937
Additional Information:
Study ID Numbers: 010104; 01-C-0104
Study Start Date: February 22, 2001
Record last reviewed: February 1, 2004
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00011778
Other Squamous Cell Carcinoma Studies:
1. A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
2. The Effects of Upper Airway and Digestive Tract Tumors on the Immune System
3. Assessment of Head and Neck Tumor Hypoxia Using 18F-Fluoromisonidazole
4. Recombinant Fowlpox Virus Vaccine to Treat Mouth and Throat Cancer
5. A Pilot Study of Paclitaxel with Radiation Therapy for Locally Advanced Head and Neck Cancer
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A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
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