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A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma Clinical Trials References presented on Clinical Trials Search isn't meant to be a substitute for proven healthcare advice, trips or professional assistance using a genuine physician. We are not docs. Always confer with your physician about A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma conditions. Clinical Trials Search.org is a site devoted to listing clinical research studies in human subjects. A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma Clinical research trials and A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma healthcare trials happen in hundreds of localities throughout the United States of America. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials usually evaluate the potency of new drugs. The propose of the studies / projects is to answer particular human health questions. Clinical trials are a popular way for mDs, government agencies, and private sector companies to detect cures for all sorts of conditions, such as A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma. A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma Clinical Trials and other clinical trials allow volunteers to acquire healthcare treatment choices before they are available to the general public. Some times the subjects recieve professional assistance for free, and every now and again they are compensated for their time. Sometimes there is a cost for a A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma clinical trial. Subjects frequently obtain the most expert healthcare possible for their A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma condition. Risks are a reality, nevertheless, and can include more or frequent doctor trips, medical risks (possibly life-threatening), and/or the treatment being uneffective. Trials are federally governed with stern guidelines to protect clinical trials patients.
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Home > "A" Clinical Trials Conditions > A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma  A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma
A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma
For Condition: Melanoma,Neoplasm Metastasis
Status: Completed
Sponsor(s): National Cancer Institute (NCI) ,
Synopsis: This phase I study will evaluate the toxicity and secondarily the response of cohorts of patients with advanced malignant melanoma treated with a combination of a replication defective adenovirus expressing the Herpes simplex virus type-1 thymidine kinase (HSV-tk) gene and escalating doses of ganciclovir (GCV). HSV-tk catalyzes the monophosphorylation of the non-toxic prodrug GCV, which is then further phosphorylated by cellular kinases and incorporated into DNA, where it inhibits its synthesis and ultimately results in cell death. Adult patients with metastatic (stage IV) malignant melanoma who are not curable by currently available treatments and who have at least one accessible, discreet, cutaneous or subcutaneous lesion of less than or equal to 3 cm(3) volume will receive intratumoral injection(s) of a 5 X 10(11) viral particles/cm(3). Forty-eight (48) hours after vector administration, patients will receive intravenous GCV every 12 hours for seven (7) days. This study will involve the escalation of the total dose of GCV administered to cohorts of patients. Patients will be closely monitored for local and systemic toxicity. Patients will also be evaluated for response of their malignant melanoma (both the treated lesion and other sites of untreated disease). The goal of this study is to determine the maximum tolerated dose (MTD) of GCV which can be administered in combination with 5 X 10(11) viral particles/cm(3) of AdV.RSV-TK, and the dose limiting toxicity (DLT) of HSV-tk gene therapy in combination with high dose GCV in a cutaneous tumor model before proceeding to clinical trials involving visceral tumors. A secondary goal will be to determine the response rate of the treated lesions and possible immunologic "bystander" effects on remote sites of untreated tumor.
Details: This phase I study will evaluate the toxicity and secondarily the response of cohorts of patients with advanced malignant melanoma treated with a combination of a replication defective adenovirus expressing the Herpes simplex virus type-1 thymidine kinase (HSV-tk) gene and escalating doses of ganciclovir (GCV). HSV-tk catalyzes the monophosphorylation of the non-toxic prodrug GCV, which is then further phosphorylated by cellular kinases and incorporated into DNA, where it inhibits its synthesis and ultimately results in cell death. Adult patients with metastatic (stage IV) malignant melanoma who are not curable by currently available treatments and who have at least one accessible, discreet, cutaneous or subcutaneous lesion of less than or equal to 3 cm(3) volume will receive intratumoral injection(s) of a 5 X 10(11) viral particles/cm(3). Forty-eight (48) hours after vector administration, patients will receive intravenous GCV every 12 hours for seven (7) days. This study will involve the escalation of the total dose of GCV administered to cohorts of patients. Patients will be closely monitored for local and systemic toxicity. Patients will also be evaluated for response of their malignant melanoma (both the treated lesion and other sites of untreated disease). The goal of this study is to determine the maximum tolerated dose (MTD) of GCV which can be administered in combination with 5 X 10(11) viral particles/cm(3) of AdV.RSV-TK, and the dose limiting toxicity (DLT) of HSV-tk gene therapy in combination with high dose GCV in a cutaneous tumor model before proceeding to clinical trials involving visceral tumors. A secondary goal will be to determine the response rate of the treated lesions and possible immunologic "bystander" effects on remote sites of untreated tumor.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: Histologically Documented Malignant Melanoma (all pathologic subtypes are eligible). Independent review of pathologic slides will be required. Patients must have advanced AJCC Stage IV (M1) disease with at least one discreet easily accessible and measurable cutaneous or subcutaneous lesion of a volume of less than 3 cm(3) by physical examination using a set of Vernier calipers. The patient must not be a candidate for curative surgical resection. Patients with visceral metastases (including brain lesions) will be eligible provided they do not have rapidly progressive CNS metastases likely to result in death within three (3) months. Measurable Disease: Any mass reproducibly measurable in three perpendicular diameters (index lesion). The index (treatment) lesion must be a discreet tri-dimensionally measurable cutaneous or subcutaneous tumor by physical examination. The index lesion must be less than or equal to 3 cm(3) in volume as calculated by the formula V (cm(3)) = l x w x h. Ulcerated or necrotic lesions may not serve as the index lesion. Other untreated sites of disease must be documented and measured (if possible). Karnofsky Performance Status greater than or equal to 60. Expected survival greater than three months. Recovery from any significant toxicity of prior surgery, radiotherapy and/or chemotherapy. Must be 18 year of age or older. PRIOR TREATMENT: Patients may have had prior surgical treatment and/or radiotherapy provided the treatment (index) lesion is not in a prior to current radiation field. Patients may receive brain radiotherapy for CNS metastases while on protocol provided the treatment lesion is not within the radiation treatment field. Patients may have received prior biological response modifier therapy (e.g., Interleukin-2, interferon) and must be equal to or greater than four weeks from the last treatment and must have recovered from any treatment related to Grade II or greater toxicity. Patients receiving prior anticancer chemotherapy will be eligible. Patients must be greater than or equal to four weeks since their last dose of chemotherapy and equal to or greater than six weeks if a nitrosourea (e.g., CCNU, BCNU), melphalan or mitomycin C was administered. Patients must have recovered from any treatment related to Grade II or greater toxicity. Patients may not have received any prior "gene therapy" using adenoviral based vectors, chimeric adenoviral based vectors, HSV-tk or other thymidine kinase based therapy. If patients have a clinical indication requiring anti-neoplastic chemotherapy, biological response modifier therapy, other gene therapy including ribozyme and antisense based therapy, or radiation therapy other than cranial irradiation for CNS metastases they will go off study. Patients may receive replacement or therapeutic corticosteroids if medically indicated while on study. REQUIRED INITIAL PARAMETERS: Granulocytes (ANC) - greater than or equal to 1,800 per microliter. Platelet count - greater than or equal to 100,000 per microliter. Hemoglobin - greater than or equal to 9.0 gm per dL. BUN - less than or equal to 1.5 times normal. Serum Creatinine - less than or equal to 1.8 mg per dL, or Creatinine Clearance - greater than or equal to 70 microliter per minute. Bilirubin - less than or equal to 1.5 times normal. Patients must be fully staged prior to entry onto study. Patients must be able to travel to the NIH Clinical Center to initiate treatment and be able to complete a seven day course of I.V. ganciclovir. Each patient must be aware of the nature of his/her disease and must willingly give consent after having a clear understanding of the investigational nature of this therapy, alternatives, potential benefits, side effects, risks and discomforts. Written informed consent must be obtained for each patients before entering the trial. Patient must not have any clinically significant medical disease other than their cancer that is poorly controlled and/or expected to impact on patient survival or ability to complete the proposed plan of treatment and follow-up monitoring. Individuals must not have significant cognitive impairment resulting in their inability to adequately understand the nature of their illness, treatment alternatives, risk and requirements of this protocol. No serious active infection requiring intravenous antibiotic or antiviral therapy. Patients must not be currently receiving ganciclovir, acyclovir or similar antiviral drug. Patients must not have clinical AIDS, primary immunodeficiencies, or be on immunosuppressive therapy (e.g., organ allograft recipients) other than medically indicated corticosteroid therapy. Patients must not have a second active cancer other than melanoma. Patients must not have a history of sensitivity to ganciclovir or other antiviral drugs of this family, or prior severe reaction to adenovirus or herpes virus infection (e.g., toxic epidermal necrolysis (TEM) or Stevens-Johnson syndrome). Patients must not be pregnant or lactating women, or women of child-bearing age not surgically sterilized or not practicing adequate contraception (oral contraceptives or barrier contraceptive method with spermicide). All women must have a negative serum pregnancy test upon entry on study.
Total Enrollment: 27
Location and Contact Information:
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
United States
Additional Information:
Study ID Numbers: 980140; 98-C-0140
Study Start Date: August 20, 1998
Record last reviewed: August 2, 2002
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00001974
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A Phase I Study of Intralesional Administration of an Adenovirus Vector Expressing the HSV-1 Thymidine Kinase Gene (AdV.RSV-TK) in Combination with Escalating Doses of Ganciclovir in Patients with Cutaneous Metastatic Malignant Melanoma
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