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A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors Clinical Trials Facts presented on Clinical Trials Search is not designed to be a substitute for certified medical advice, travels to or professional assistance by using a genuine doctor. We aren't mDs. Always consult your physician about A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors conditions. Clinical Trials Search.org is a website committed to listing clinical research studies in human subjects. A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors Clinical research trials and A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors health trials occur in a lot of of cities throughout the US. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials generally evaluate the potency of new does drugs. The role of the studies / undertakings is to figure out specific human healthcare questions. Clinical trials are a popular manner for mDs, government agencies, and private sector companies to locate treatments for all sorts of conditions, including A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors. A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors Clinical Trials and other clinical trials permit volunteers to get medical treatment choices before they are available to the general public. Many times the test subjects get professional assistance for free of charge, and occasionally they are compensated for their time. Sometimes there is a cost for a A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors clinical trial. Human subjects often get the best healthcare possible for their A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors condition. Risks are a reality, nevertheless, and could include additional or frequent dr. calls, medical hazards (perhaps life-threatening), and/or the treatment being ineffectual. Trials are federally governed with exacting guidelines to protect clinical trials patients.
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Home > "A" Clinical Trials Conditions > A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors  A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors
A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors
For Condition:
Status: Recruiting
Sponsor(s): National Cancer Institute (NCI) ,
Synopsis: This is a Phase I trial of CEA-TRICOM based vaccine in patients with CEA positive solid tumors, metastatic to the liver, who have completed at least one chemotherapy regimen for metastatic disease. There are two cohorts of this trial. The first cohort of patients will receive vaccine and radiation therapy to the liver lesion(s), at a dose and schedule designed to induce immunomodulatory effects (e.g. upregulation of Fas) and thus augment the T-cell mediated tumoricidal activity induced by the vaccine. The second cohort of patients will receive the same vaccine and radiation, and in addition receive celecoxib. All vaccines will be given at the National Naval Medical Center (NNMC) and all radiation will be given at NIH Clinical Center. The basic vaccination will incorporate a priming vaccination with rV-CEA(6D)/TRICOM followed by serial boosting vaccinations with rF-CEA(6D)/TRICOM. Each vaccination will be given with rF-GM-CSF at the same site as the vaccination. In a Phase I trial completed at Georgetown University using this vaccine regimen, CEA-specific immune responses were seen in all A2+ patients, and there is preliminary evidence of clinical benefit in some patients with advanced cancer.(1) The rationale for the addition of radiation and celecoxib to this trial comes from a series of preclinical experiments and clinical observations, in which we and others have shown that (A) radiation can upregulate Fas on tumor cells and potentiate T-cell mediated killing of tumor, (B) cyclo-oxegenase-2 (COX-2) inhibitors have been shown to be radiosensitizers and can have synergistic anti-tumor responses when combined with radiation, (C) COX-2 inhibitors are compatible with this vaccine in terms of immunologic responses, and additive in terms of tumors responses, and (D) the use of vaccine and radiation inhibition is safe in preclinical models and in several patients in an ongoing clinical trial. In addition, others have shown that radiation to the liver is well tolerated at doses similar to what we propose, and although not used in standard treatment, may have some palliative benefit. Thus we propose to use a dose of radiation to liver metastasis and daily celecoxib, both of which have been shown to augment the anti-tumor effect of CEA/TRICOM vaccines in preclinical studies. It is important to note that the radiation to tumor and COX-2 inhibitor strategies are designed not primarily to enhance the activity of the immune response, but to enhance tumor kill induced by the vaccine by altering the phenotype of the tumor.
Details: This is a Phase I trial of CEA-TRICOM based vaccine in patients with CEA positive solid tumors, metastatic to the liver, who have completed at least one chemotherapy regimen for metastatic disease. There are two cohorts of this trial. The first cohort of patients will receive vaccine and radiation therapy to the liver lesion(s), at a dose and schedule designed to induce immunomodulatory effects (e.g. upregulation of Fas) and thus augment the T-cell mediated tumoricidal activity induced by the vaccine. The second cohort of patients will receive the same vaccine and radiation, and in addition receive celecoxib. All vaccines will be given at the National Naval Medical Center (NNMC) and all radiation will be given at NIH Clinical Center. The basic vaccination will incorporate a priming vaccination with rV-CEA(6D)/TRICOM followed by serial boosting vaccinations with rF-CEA(6D)/TRICOM. Each vaccination will be given with rF-GM-CSF at the same site as the vaccination. In a Phase I trial completed at Georgetown University using this vaccine regimen, CEA-specific immune responses were seen in all A2+ patients, and there is preliminary evidence of clinical benefit in some patients with advanced cancer.(1) The rationale for the addition of radiation and celecoxib to this trial comes from a series of preclinical experiments and clinical observations, in which we and others have shown that (A) radiation can upregulate Fas on tumor cells and potentiate T-cell mediated killing of tumor, (B) cyclo-oxegenase-2 (COX-2) inhibitors have been shown to be radiosensitizers and can have synergistic anti-tumor responses when combined with radiation, (C) COX-2 inhibitors are compatible with this vaccine in terms of immunologic responses, and additive in terms of tumor responses, and (D) the use of vaccine and radiation inhibition is safe in preclinical models and in several patients in an ongoing clinical trial. In addition, others have shown that radiation to the liver is well tolerated at doses similar to what we propose, and although not used in standard treatment, may have some palliative benefit. Thus we propose to use a dose of radiation to liver metastasis and daily celecoxib, both of which have been shown to augment the anti-tumor effect of CEA/TRICOM vaccines in preclinical studies. It is important to note that the radiation to tumor and COX-2 inhibitor strategies are designed not primarily to enhance the activity of the immune response, but to enhance tumor kill induced by the vaccine by altering the phenotype of the tumor.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA Solid Tumors expressing CEA positive cancer with metastatic liver lesions as the life-threatening aspect of the disease (as a guideline, metastatic liver lesions should be at least approximately 75% of total tumor burden). Tumor that has been shown to express CEA by positive immunohistochemical techniques (staining of at least 20% of cells will be considered positive) or have had an elevated serum CEA greater than 10 ng/ml at any point during their disease course. Completed at least one chemotherapy regimen for metastatic disease. 18 years of age or greater. Life expectancy greater than or equal to 6 months. Able to understand and give informed consent. ECOG performance status of 0 - 1. Serum creatinine within the institution limits of normal OR creatinine clearance on a 24 hour urine collection of 60 mL/min or greater, total bilirubin within the institution limits of normal and AST less than or equal to twice the institution upper limits of normal. Vaccinia-naive or vaccinia immune. Recovered completely from any reversible toxicity associated with recent therapy. Typically this is 3-4 weeks for patients who most recently received cytotoxic therapy except for the nitrosoureas and mitomycin C for which 6 weeks is needed for recovery. At least 4 weeks after cytotoxic therapy with complete recovery of reversible toxicity. At least 3 of the 6 patients in each cohort must be HLA-A2 positive. (If none of the first three patients in a cohort are A2 positive, then subsequent patients will be prescreened for A2 positivity prior to enrollment.) Hematological eligibility parameters (within 16 days of starting therapy): Granulocyte count of 1,500/mm3 or greater Platelet count of 100,000/mm3 or greater Hgb of 8 Gm/dL or greater Absolute lymphocyte count of 400/mm3 or greater PT/PTT within the institution limits of normal. Prior Immunotherapy will be allowed Serum Beta-HCG less than 5.0 microIU/mL in females (with child bearing potential). EXCLUSION CRITERIA Patients should have no evidence of being immunocompromised as listed below. -Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects -Autoimmune diseases such as, Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome active Grave's disease. Altered immune function in prospective participants will be assessed through a thorough history and physical examination. Any clinical suspicion of autoimmune dysfunction will be worked up before enrollment on to the study. This requirement is due to the potential risks of exacerbating autoimmunity -Hepatitis B or C positivity -Prior radiation to greater than 50% of all nodal groups -Prior liver radiation -Concurrent use of nonsteroidal anti-inflammatory drugs -Concurrent use of systemic steroids, except for physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Steroid eye drops are contraindicated for at least 2 weeks prior vaccinia vaccination and at least 4 weeks post vaccinia vaccination. -Prior splenectomy History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen. Pregnant or breast-feeding women. Recombinant vaccinia vaccination should not be administered if any of the following apply to either recipients, or for at least three weeks after vaccination (i.e., until the scab has separated from the skin and the underlying skin has healed), their close household contacts (close household contacts are those who share housing or have close physical contact): persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 5 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection. Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis. Known brain metastasis, history of seizures, encephalitis, or multiple sclerosis. Concurrent chemotherapy. Serious hypersensitivity reaction to egg products. Clinically significant cardiomyopathy requiring treatment. For Cohort II only: known hypersensitivity to celecoxib, or allergic reaction to sulfonamides. For Cohort II only: History of peptic ulcer or gastrointestinal bleeding deemed as clinically significant by the investigator. For Cohort II only: Known hypersensitivity to aspirin or other NSAID's and aspirin-sensitive asthma. For Cohort II only: Concurrent use of inhibitors of P450 2C9, or concurrent fluconazole or lithium therapy. Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with ordinary physical activity (New York Heart Association class 2 or greater) are not eligible. Patients with pulmonary disease that have fatigue or dyspnea with ordinary physical activity are not eligible. Patients who have objective evidence of congestive heart failure by physical exam or imaging are not eligible.
Total Enrollment: 12
Location and Contact Information:
National Cancer Institute (NCI) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 040167; 04-C-0167
Study Start Date: April 20, 2004
Record last reviewed: April 15, 2004
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00081848
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A Phase I Trial of a CEA-TRICOM Based Vaccine and Radiation to Liver Metastasis with or without cCelecoxib in Patients with CEA Positive Solid Tumors
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