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Approximately 20 percent of corneal transplant patients, about 6,000 per year, face donor tissue rejection at rates of up to 60 percent because of corneal vascularization or prior graft rejection. Histocompatibility antigen matching and/or crossmatching may have offered these patients an improved chance for successful outcome.~The Collaborative Corneal Transplantation Studies Group conducted two controlled, double-masked studies addressing distinct scientific questions about donor-recipient histocompatibility matching. The Crossmatch Study was a randomized study assessing the effectiveness of crossmatching in preventing graft rejection among high-risk patients with lymphocytotoxic antibodies. The Antigen Matching Study was a prospective, double-masked, observational study of the effectiveness of HLA-A, -B, and -DR donor-recipient matching in high-risk patients who had no lymphocytotoxic antibodies.~Six clinical centers recruited high-risk patients and collaborated with their local eye banking and organ procurement agencies in procuring donor corneal tissue. For each of the two studies, a total of 400 patients were sought. Blood samples from each enrolled patient were sent to the local CCTS tissue typing laboratory for HLA typing, and serum samples were sent to the Central Laboratory to be screened for preformed lymphocytotoxic antibodies. Depending on the results of the testing, patients were entered into the Crossmatch Study or the Antigen Matching Study.~As corneal donors became available, donor blood samples were HLA typed at the local laboratories and crossmatched against all CCTS patients who awaited transplantation. Results of the testing were entered in a national, 24-hour computerized allocation system operated by the United Network for Organ Sharing (UNOS). Patients in the Crossmatch Study received a cornea from either a positively crossmatched donor or a negatively crossmatched donor. Patients in the Antigen Matching Study received a cornea with 0 to 6 matched antigens.~Transplant patients were followed intensively during the first months after surgery. The number of clinic visits was tapered to 2 during the third and final year of followup, resulting in a total of 17 postoperative visits. Irreversible failure of the corneal allograft due to all causes was the primary outcome variable in both studies. Allograft reaction episodes, irreversible failure due to rejection, and visual acuity were secondary outcome variables. | To determine whether histocompatibility matching of corneal transplant donors and recipients can reduce the incidence of graft rejection in high-risk patients. |
BACKGROUND:~Infection remains a major cause of death in patients receiving chemotherapy for malignant diseases. One approach to the problem of septicemia and high mortality in these patients was the therapeutic use of granulocyte transfusions. Improvements in collection techniques, employing continuous flow centrifugation, permitted the collection of granulocytes from a single, normal donor in sufficient numbers to study their application in the treatment of infections in granulocytopenic patients. Studies had demonstrated the efficacy of granulocyte transfusions as an adjunct in the therapy of septicemia due to gram negative microorganisms associated with granulocytopenia.~The aims of the study were to determine (1) whether infections could be prevented in patients who received granulocytes prophylactically and (2) whether recovery from infection was aided in patients who received granulocytes therapeutically. Both trials utilized controls who received no granulocytes.~Four contracts were awarded in September 1976. The protocol designed to evaluate the efficacy of prophylactic granulocyte transfusions was completed at the close of 1977. The protocol for the therapeutic trial was completed in April 1978. Approximately 90 patients were randomized in the prophylactic trial and 51 in the therapeutic trial. The Recruitment and Intervention Phase ended in February 1980. The trial has concluded.~DESIGN NARRATIVE:~Prophylactic Trial and Therapeutic Trial: randomized, non-blind, sequential. Eligible patients were randomized to daily granulocyte transfusions or no granulocyte transfusions.~The study completion date listed in this record was inferred from the first publication listed in the Citations section of this study record. | To evaluate granulocyte transfusion therapy with respect to its prophylactic and therapeutic effectiveness to prevent and aid recovery from infection. The study trials were conducted simultaneously. |
Renal transplantation is recognized as the treatment of choice for children with chronic renal failure. However, patient and graft survival rates in young children are unacceptably low. In preliminary studies, OKT3 (a monoclonal antibody) induction therapy received post transplant has been more successful than standard immunosuppression alone in improving graft survival. This study is designed to assess the impact of induction therapy on graft survival in pediatric kidney transplant patients.~Patients are assigned to OKT3 induction or no induction in a 1:1 ratio. Randomization to oral cyclosporine of either Sandimmune or Neoral is also done in a 1:1 ratio. Group 1 receives OKT3 intraoperatively followed by Neoral. Group 2 receives OKT3 intraoperatively followed by Sandimmune. OKT3 is administered at 2.5 mg (if weight less than 30 kg) or 5 mg (if weight above 30 kg) per day for a maximum of 14 days. Group 3 receives IV cyclosporine followed by Neoral. Group 4 receives IV cyclosporine followed by Sandimmune. Oral cyclosporine is administered in a masked preparation. The dose for Sandimmune and Neoral is the same; patients 6 years of age and older begin at a dose of 15 mg/kg/day and patients under 6 years of age receive 500 mg/m2/day. Patients will receive concomitant medications including steroids (IV and po), Nifedipine, anti-CMV therapy, Bactrim, Azathioprine or Mycophenolate Mofetil. Kidney function, incidence of viral infection, graft survival, and incidence of malignancy will be measured to assess the role of OKT3 induction and the role of rejection in graft failure. Graft function will be evaluated at 1-, 2-, and 4-year intervals. | Kidney transplantation is often successful. However, despite aggressive anti-rejection drug therapy, some patients will reject their new kidney. This study is designed to test two anti-rejection approaches. Two medications in this study are currently used in children, but there is no information regarding which drug is safer or more effective.~Survival rates in renal transplantation are unacceptably low. Therefore, there is a need for an improved post-transplant treatment, such as the induction therapy used in this study. |
NMR imaging promises to provide useful and unique diagnostic information in a variety of diseases. In an attempt to evaluate its role, we plan to study a wide range of diseases during the initial year of imaging. Exposure to magnetic fields and radiofrequency energies of this magnitude have demonstrated no deleterious effects clinically or in the laboratory. The only restrictions will be those imposed by ferromagnetic objects within the patient which would increase the risk of placing them in a strong magnetic field. | This protocol is designed to investigate the use of novel techniques in MRI that may not yet be commercially available. Specifically, the protocol enables patients to take advantage of new pulse sequence software, coil design or post processing capabilities not otherwise available. The informed consent explains MRI in lay terms, describes the use of contrast agents and lists contraindications to MRI. |
Background:~It may be in the interest of the CCR to continue to follow and treat certain subjects after they have completed their treatment and participation on a research protocol.~Objective:~To provide continuing treatment and medical follow-up for CCR subjects who have completed their treatment and participation on a research protocol and who are not currently entered on or eligible for another active research protocol.~Eligibility:~Subjects who have been previously enrolled on and received treatment according to an approved CCR research protocol. (clinical trial)~It is in the best interest of the subject and the CCR for the subject to continue to receive standard care and follow-up at the NIH.~Design:~Medical/surgical/radiotherapeutic care, treatment and follow-up is provided for CCR subjects who have completed their treatment and participation on a research protocol and who are not currently entered on an active research protocol.~No investigational treatments will be administered. This protocol is not be used as a platform to perform pilot studies of off-label uses for standard agents. | This protocol is to provide continuing medical/surgical/radio-therapeutic care, treatment and follow-up for NCI patients not currently entered on an active research protocol. No investigational treatments will be administered on this protocol. |
Objective:~Our goal is to study the functional organization of the intact human brain by combining cognitive tasks and neuroimaging. Functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG) and electroencephalography (EEG) will be used to measure brain activity in healthy human subjects engaged in performing cognitive tasks. These tasks will address specific questions concerning the neural systems that mediate perception, attention, memory, decision-making, emotion, plasticity and social interactions. fMRI and MEG, respectively, will be employed to investigate the spatial and temporal aspects of these neural systems.~Study Population:~Normal volunteer participants aged 18-65, who are in good general health will be recruited from the local community and studied under this minimal risk protocol.~Design:~Subjects will perform cognitive tasks in behavioral and/or neuroimaging sessions (fMRI or MEG).~Outcome Measures:~Behavior as performance on cognitive tasks, and brain activity (fMRI and MEG) will be combined to yield information about the neural correlates and processes underlying different aspects of human cognition including visual perception, memory, learning, emotion, social cognition, decision-making and attention. | The purpose of this study is to use brain imaging technology to measure changes in blood flow to areas in the brain as individuals perform intellectual tasks.~This study will use functional magnetic resonance imaging (fMRI) to examine blood flow to areas of the brain as participants engage in tasks associated with visual perception, visual recognition, and memory.... |
The MTD and biochemically active dose of FUDR as a 24-hour and gemcitabine as a 2-hour infusion will be determined first (Part A); if the biochemically active FUDR dose is less than the MTD, new patients will be entered to determine the maximum tolerated duration of FUDR infusion (Part B). | The purpose of this study is to determine the clinical toxicities associated with administering sequential dFdC as a one hour infusion followed by a continuous infusion of FUdR over 24 hours with low dose oral LV weekly for three weeks out of four. |
The National Marrow Donor Program (NMDP) was established in 1987 in order to (1) create a registry of volunteer, prospectively tissue-typed, unrelated bone marrow donors, (2) facilitate the performance of matched unrelated donor marrow transplants through a coordinated circuit of Donor Centers, Collection Centers and Transplant Centers throughout the United States, and (3) evaluate the outcome of such transplants and identify future areas of research in the field of unrelated donor marrow transplants. The NIH Marrow Donor Center, a participant in the NMDP, is currently the second largest hospital-based Donor Center in the nation, with approximately 55,900 active donors on its registry. 402 NIH unrelated donors to date have undergone 429 marrow or blood stem cell harvest for an NMDP recipient, and the current rate of such harvests is three per month. Once an HLA-matched donor in the NIH Donor Center registry is identified through the NMDP computer network, the donor must undergo a medical evaluation to determine suitability for marrow harvest. This evaluation consists of a medical history, a physical examination, routine blood work, EKG, chest x-ray, and urinalysis, and generally takes 4 to 6 weeks. A third party non-NIH physician usually performs the evaluation, with the costs reimbursed by the NMDP. Occasionally, an expedited evaluation of an unrelated donor must be performed, due to the urgency of the need for a transplant in the recipient, and there is insufficient time to accomplish this work-up using the routine third-party physician's office mechanism. This protocol shall provide a means by which prospective NIH unrelated marrow donors participating in the NMDP program can undergo an expedited medical evaluation to determine suitability for marrow donation. It is expected that not more than 5 to 10 donors per year shall require such expedited evaluation. | Individuals interested in becoming prospective bone marrow donors and joining the Registry of the National Marrow Donor Program (NMDP) should do so by calling 301-496-0572, the phone number of the NIH Marrow Donor Center. An appointment will be made to have a health history taken and to have a buccal swab collected for tissue (HLA) typing. The current protocol only involves donors already registered with the NMDP, who have been identified as perfect matches for an unrelated patient requiring a bone marrow transplant, and who require expedited medical evaluation prior to marrow collection. |
Background:~Patients enrolled on CCR clinical protocols may require long term follow-up to assess outcome (e.g., survival) or the effects of prior therapy.~Keeping the primary treatment protocols open after accrual is complete in order to follow patients for long term outcome is an administrative burden on investigators and the IRB.~Objectives:~-To provide follow-up for patients who are long term survivors previously enrolled Center for Cancer Research (CCR) trial but who may not currently be enrolled on a research protocol.~Eligibility:~-Patients who were previously enrolled on a CCR protocol and who are not eligible for an active NCI intramural primary research protocol.~Design:~The medical procedures/tests will be based on the patient's diagnosis, treatment and supporting clinical information. This is a follow-up study in which only standard tests and procedures are to be performed.~Clinical information that is relevant to the patients prior protocols will be collected for research purposes.~Procedures that entail more than minimal risk to the patient should not be performed for research purposes on this protocol. | This protocol is to provide follow-up medical/surgical visits for DCS patients who are long term survivors and may not currently be a participant entered on an active research protocol. No investigational treatments or standard treatments will be administered on this protocol. |
Acquisition of fresh tumor and normal tissue samples is necessary for the preparation of cDNA libraries, microarray chips, tissue specific probes, and proteomics development and validation. This protocol will allow acquisition of patient samples at the time of tissue sampling for surgery, diagnostic tests, or therapeutic phereses. These samples will be forwarded without patient identifiers, pathology reports, or other labels. Tissue pathology will be verified within the Laboratory of Pathology and samples used strictly for CGAP and Proteomic Initiative indications. | Acquisition of fresh tumor and normal tissue samples are necessary for the preparation of cDNA libraries, microarray chips, and tissue specific probes, and proteomics development and validation. This protocol will allow acquisition of samples at the time of tissue sampling for surgery, diagnostic tests, or therapeutic phereses. These samples will be forwarded without patient identifiers, pathology reports, or other labels. Tissue pathology will be verified within the Laboratory of Pathology and samples used strictly for CGAP and Proteomic Initiative indications. |
This study will examine the role of temperature in modulating aspects of energy metabolism in human skeletal muscle. Tests will be conducted at rest and during concentric dorsiflexion exercise of the Tibialis anterior (TA) muscle using an existing custom-designed dynamometer in conjunction with mild local heating and cooling. Magnetic resonance spectroscopy (MRS), performed in a 4-tesla whole-body NMR system, will be used to non-invasively measure muscle temperature and energy-state. Specifically these tests will assess the extent to which temperature changes occur during aerobic exercise and how small temperature changes affect mitochondrial function in-vivo. | This study will examine the role of temperature in changing energy metabolism in human muscle. In order to do this, researchers will use magnetic resonance imaging (MRI) to provide information about how parts of muscle operate during exercise.~Magnetic resonance imaging (MRI) is a diagnostic tool that creates high quality images of the human body without the use of X-ray (radiation). In this study, MRI will be used to measure the temperature and energy level of specific muscles during rest and exercise. In addition, the muscles being tested will be heated and cooled to see if temperature directly affects levels of energy in muscle. |
Proper functioning of recently acquired P-CCMB cardiopulmonary exercise equipment will be verified by testing healthy volunteers. In addition, quality control will be verified by performing monthly testing of healthy volunteers as biologic standards. | This study is designed to make sure exercise equipment used by the National Heart, Lung, and Blood Institute is working properly. Healthy volunteers will be requested to use P-CCMB cardiopulmonary exercise equipment (treadmills and exercise bicycles) two times a month to ensure the machines are functioning properly. |
OBJECTIVES: I. Evaluate the clinical feasibility and toxicity of monoclonal antibody OKT3 given with low-dose cyclophosphamide in patients with advanced malignancies. II. Perform serial immune monitoring on patients treated with this regimen. III. Identify any clinical responses produced by this regimen.~OUTLINE: Biological Response Modifier Therapy with Suppressor Cell Inhibition. Anti-CD3 Murine Monoclonal Antibody OKT3, MOAB OKT3; with Cyclophosphamide, CTX, NSC-26271.~PROJECTED ACCRUAL: At least 9 evaluable patients per diagnostic category will be required initially; if any response is seen during the dose-finding portion of the study, a total of 24 patients with that diagnosis will be entered. | RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.~PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody and cyclophosphamide in treating patients with metastatic cancer. |
OBJECTIVES: I. Determine whether secondary cytoreductive surgery improves the progression-free interval and survival in patients with suboptimally resected stage III ovarian epithelial carcinoma treated with paclitaxel/cisplatin. II. Determine the morbidity of secondary cytoreductive surgery in these patients. III. Assess prospectively the quality of life (QOL) of these patients and determine whether secondary cytoreductive surgery affects QOL.~OUTLINE: Randomized study. Following treatment on Regimen A, patients with stable or objective response are randomized to Arms I and II. Regimen A: 2-Drug Combination Chemotherapy. Paclitaxel (Bristol-Myers), Taxol, NSC-125973; Cisplatin, CDDP, NSC-119875. Arm I: Surgery followed by 2-Drug Combination Chemotherapy. Laparotomy with resection of residual disease; followed by Taxol/CDDP. Arm II: 2-Drug Combination Chemotherapy. Taxol; CDDP.~PROJECTED ACCRUAL: Approximately 470 patients will be entered over 20 months to provide 400 evaluable patients. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug or combining chemotherapy with surgery may kill more tumor cells.~PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy consisting of paclitaxel and cisplatin with or without surgery in treating patients with stage III ovarian epithelial cancer. |
OBJECTIVES:~I. Determine the maximum tolerated dose and quantitative and qualitative toxic effects of topotecan and paclitaxel in patients with solid tumors.~II. Determine the antitumor activity of this regimen in these patients.~OUTLINE: This is a dose escalation study of topotecan and paclitaxel.~Patients receive paclitaxel IV over 3 hours on day 1 followed 2-6 hours later by topotecan IV continuously on days 1-14. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of topotecan and paclitaxel until the maximum tolerated dose (MTD) of each drug is determined. The MTD is defined as the highest dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.~PROJECTED ACCRUAL: Approximately 10-20 patients will be accrued for this study within 8-12 months. | Phase I trial to study the effectiveness of paclitaxel plus topotecan in treating patients who have solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. |
OBJECTIVES: I. Determine the biochemical modulation dose l of O6-benzylguanine (BG), defined as the dose at which baseline O6-alkylguanine DNA alkyltransferase (AGT) activity in circulating peripheral blood mononuclear cells (PBMC) decreases by greater than 90% in patients with advanced solid tumors at 2 hours after BG infusion. II. Determine the biochemical modulation dose t/18 (BMDt/18) of BG, defined as the dose at which AGT activity in human metastatic tumor tissue decreases to undetectable levels at 18 hours after BG infusion. III. Determine the maximum tolerated dose of carmustine (BCNU) when administered with BG at the BMDt/18 in these patients. IV. Determine the toxicities of BG and BCNU in these patients. V. Determine the pharmacokinetic parameters of BG administered at the BMDt/18, and determine any effects of BCNU on BG pharmacokinetics. VI. Assess any antitumor response in patients with metastatic solid tumors treated with this regimen. VII. Determine the effect of lower, more frequent bolus doses or a continuous infusion of BG on the depletion of AGT activity in PBMC and tumor tissue in these patients. VIII. Determine the pharmacokinetics of BG in lower, more frequent bolus doses or continuous infusion.~OUTLINE: This is a dose escalation study of 06-benzylguanine (BG) and carmustine (BCNU). Patients receive BG IV over 1 hour during week 1, and then BG IV over 1 hour followed 1 hour later by BCNU IV over 1 hour during week 3. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 1-3 patients receive escalating doses of BG until the biochemical modulation dose l (BMDl) is determined. The BMDl is defined as the dose at which baseline O6-alkylguanine DNA alkyltransferase (AGT) activity in circulating peripheral blood mononuclear cells decreases by greater than 90% at 2 hours after BG infusion. Cohorts of 3 patients receive escalating doses of BG beginning at the BMDl until the biochemical modulation dose t/2 (BMDt/2) is determined. The BMDt/2 is defined as the dose at which AGT activity in human metastatic tumor tissue decreases by greater than 90% at 2 hours after BG infusion. Cohorts of 3 patients receive escalating doses of BG beginning at the BMDt/2 until the biochemical modulation dose t/18 (BMDt/18) is determined. The BMDt/18 is defined as the dose at which AGT activity in human metastatic tumor tissue decreases to undetectable levels at 18 hours after BG infusion. Patients then receive BG IV over 1 hour followed 1 hour later by BCNU IV over 1 hour during week 1. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of BCNU combined with BG at the BMDt/18 until the maximum tolerated dose (MTD) of BCNU is determined. The MTD of BCNU is defined as the dose preceding that at which 2 or more of 6 patients experience dose limiting toxicity. A cohort of 3 patients receives BG IV over 2 minutes and another cohort of 3 patients receives BG IV over 24 hours. An additional cohort of 6 patients receives BG IV over 24 hours and BCNU IV over 1 hour beginning 2 hours into BG infusion during week 3.~PROJECTED ACCRUAL: A total of 51 patients will be accrued for this study over 36 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of O(6)-benzylguanine and carmustine in treating patients who have solid tumors. |
OBJECTIVES: I. Determine whether adoptive immunotherapy comprising donor-derived CD8+, CMV-specific, major histocompatibility complex class I-restricted cytotoxic T-lymphocyte (CTL) clones (CD8+ CMV-specific CTL clones) and CD4+ CMV-specific T-helper (Th)-cell clones is effective in preventing CMV viremia and disease in CMV-positive patients with malignancies requiring allogeneic bone marrow or peripheral blood stem cell transplantation. II. Determine whether the transfer of CD4+ CMV-specific Th-cell clones to patients with deficient responses can reconstitute CD4+ Th-cell activity and augment adoptively transferred CD8+ CMV-specific CTL clones.~OUTLINE: Allogeneic CD8+ CMV-specific, major histocompatibility complex class I-restricted cytotoxic T-lymphocyte (CTL) clones (CD8+ CMV-specific CTL clones) and CD4+ CMV-specific T-helper (Th)-cell clones are harvested and cultured in vitro at least 2 weeks before bone marrow or peripheral blood stem cell (PBSC) transplantation. Bone marrow or PBSC are infused on day 0. Patients receive the first infusion of CD8+ CMV-specific CTL clones beginning between days 28 and 45 posttransplantation, followed 8 days later by the second infusion, followed 2 days later by the first infusion of CD4+ CMV-specific Th-cell clones. Patients who receive prednisone posttransplantation or have deficient CD8+ CTL responses (i.e., less than 50% of the response measured in the immunocompetent bone marrow donor) after the second infusion of CD8+ CMV-specific CTL clones receive a third infusion of CD8+ CMV-specific CTL clones and a second infusion of CD4+ CMV-specific Th-cell clones before day 67.~PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 12-18 months. | RATIONALE: White blood cells from donors who have been exposed to cytomegalovirus may be able to help prevent this infection from occurring in patients who are undergoing bone marrow or peripheral stem cell transplantation.~PURPOSE: Phase II trial to study the effectiveness of donated white blood cells to prevent cytomegalovirus infection in patients who are undergoing bone marrow or peripheral stem cell transplantation. |
OBJECTIVES: I. Determine the complete histologic response rate (which represents the rate of organ preservation) to induction with cisplatin/fluorouracil followed by radiotherapy plus cisplatin in patients with selected stage III/IV cancer of the hypopharynx or base of the tongue. II. Evaluate the feasibility of accruing and treating patients with this regimen in a multi-institutional setting. III. Determine the overall complete response rate in these patients.~OUTLINE: This is a multicenter study. Patients are stratified according to center and tumor site (hypopharynx vs base of tongue). Base of tongue stratum closed as of November 15, 1998. Regimen A: Patients receive cisplatin IV over 90 minutes on days 1 and 22 and fluorouracil IV over 120 minutes on days 1-5 and 22-26. Patients with measurable neck nodes discontinue therapy if disease has progressed by day 22. All patients who achieve complete or partial response at day 43 proceed to regimen B. All others proceed to resection followed by radiotherapy (off study). Regimen B (begins within 3-4 weeks of start of second induction course): Patients receive cisplatin IV over 90 minutes every 3 weeks for 3 courses. Concurrently, patients receive radiotherapy 5 days a week for 5.6 weeks. Patients are reassessed at 8-12 weeks after radiotherapy. Patients who are disease free are observed. Other patients undergo surgical resection of nodes and/or primary tumor. Patients are followed every 4-6 weeks for 1 year, every 2 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, then annually thereafter.~PROJECTED ACCRUAL: Up to 70 patients (35/tumor site) will be accrued for this study over 3.5 years. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.~PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and radiation therapy in treating patients with stage III or stage IV cancer of the hypopharynx or tongue. |
OBJECTIVES:~Evaluate the feasibility of administering 2 courses of high dose chemotherapy consisting of etoposide, cisplatin, and cyclophosphamide followed by ifosfamide, carboplatin, and paclitaxel (IC-T), each administered with filgrastim (G-CSF) and autologous stem cell support, to patients with advanced carcinomas.~Describe the toxicity of these high dose chemotherapy regimens.~Define the maximum tolerated dose of paclitaxel deliverable in this high dose regimen.~Describe the pharmacokinetics of escalating doses of paclitaxel given as a 24-hour continuous infusion.~Determine the disposition of carboplatin administered in the IC-T regimen.~OUTLINE: At least 4 weeks prior to chemotherapy, patients undergo stem cell collection following filgrastim (G-CSF) mobilization. Sufficient stem cells to support 2 courses of chemotherapy are required. Autologous bone marrow is collected as an adjuvant if stem cell harvest is inadequate.~Patients then receive high dose cisplatin, etoposide, and cyclophosphamide over 10 days, followed the next day by infusion of one fourth of the allotted stem cells, with the remaining allotment infused 2 days later. G-CSF is given for granulocyte support.~Beginning no sooner than 14 weeks from the start of the first course of chemotherapy, stable and responding patients receive high dose paclitaxel, carboplatin, and ifosfamide over 5 days, followed 2 days later with one-fourth of the allotted stem cells, with the remaining allotment infused the following day. G-CSF is given for granulocyte support. Groups of 3-6 patients are treated with escalating doses of paclitaxel until the maximum tolerated dose for this regimen is determined.~Patients are followed monthly for 1 year, every 3 months for 1 year, then as needed at the physician's discretion for at least 5 years.~PROJECTED ACCRUAL: Three to six patients will be entered at each dose of paclitaxel studied. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating patients who have advanced cancer. |
OBJECTIVES: I. Determine the maximum tolerated dose of ICI D1694 (TDX) when given with irinotecan (CPT-11) every 3 weeks in patients with advanced solid malignancies. II. Describe the pharmacokinetics of TDX and CPT-11 when given in combination. III. Investigate the relationship between topoisomerase I expression in peripheral mononuclear cells and myelosuppression and/or gastrointestinal toxicity. IV. Investigate the effect of CPT-11 on thymidylate synthase expression in tumor.~OUTLINE: This is a dose-escalating study to determine the maximum tolerated dose (MTD) of ICI D1694 (TDX) given in combination with irinotecan. Irinotecan is given intravenously on day 1 and ICI D1694 intravenously on day 2. Treatment is repeated every 3 weeks until disease progression or unacceptable toxicity intervenes. Cohorts of 3-6 patients receive escalated doses of TDX until the MTD is defined; an additional 10-12 patients will be entered at the MTD to confirm this as a recommended phase II dose.~PROJECTED ACCRUAL: 30-35 patients will be entered. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of irinotecan plus ICI D1694 in treating patients with advanced solid tumors. |
OBJECTIVES: I. Determine the maximum tolerated dose and toxicities of KRN5500 in patients with solid malignant tumors. II. Characterize the clinical pharmacokinetics of KRN5500 in this patient population. III. Initiate the preliminary evaluation of antitumor activity of KRN5500 in these patients. IV. Determine the recommended Phase II dose of KRN5500.~OUTLINE: This is a dose escalation study. Patients receive KRN5500 IV over 1 hour on days 1-3. Courses repeat every 21 days. Patients with stable disease and partial or complete remission continue treatment for 6 months beyond complete remission. Cohorts of 3 to 6 patients receive escalating doses of KRN5500. The maximum tolerated dose is defined as the dose preceding that at which at least 2 of 6 patients experience dose limiting toxicity.~PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study over 9-12 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to evaluate the effectiveness of KRN5500 in treating patients with metastatic solid tumors. |
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of irinotecan administered in combination with paclitaxel in patients with metastatic or recurrent malignancies. II. Evaluate the toxicity and safety of this combination regimen in this patient population. III. Determine the pharmacokinetic profile of irinotecan in combination with paclitaxel on a weekly schedule and if the sequence of administration influences irinotecan pharmacokinetics in these patients. IV. Determine pharmacodynamic models of irinotecan and its SN-38 and SN-38G metabolites when administered in this weekly combination schedule.~OUTLINE: This is a dose escalation study of irinotecan. Patients receive irinotecan IV concurrently with paclitaxel IV weekly. Patients demonstrating stable disease or partial or complete clinical response continue with treatment as long as dose limiting toxicities are not observed and adequate performance status is maintained. Cohorts of 3 patients receive escalating doses of irinotecan until the maximum tolerated dose is determined or 150 mg/m2 is reached.~PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of irinotecan and paclitaxel in treating patients with metastatic or recurrent cancer. |
OBJECTIVES:~Determine the maximum tolerated dose, toxicities, and preliminary antitumor activity of escalating doses of topotecan, with filgrastim (G-CSF) and peripheral blood stem cell support, when administered to patients with refractory malignancies for which no effective therapy exists.~OUTLINE: This is a dose-escalation study.~Prior to stem cell harvesting, patients receive 1-2 courses of mobilizing salvage chemotherapy.~After stem cell harvest, high-dose topotecan is administered according to an escalating dosage scale. Topotecan is given over 30 minutes daily for three days. A minimum of 3 patients are entered at each dose level. The MTD is defined as the dose immediately below that at which 2 patients experience dose limiting toxicity.~Peripheral blood stem cells (PBSC) are infused at least 24 hours after treatment with topotecan is complete. Filgrastim (G-CSF) is administered subcutaneously beginning on the day PBSC are infused and continuing until blood counts recover.~Patients are followed every 3 months for 1 year and then every 6 months thereafter.~PROJECTED ACCRUAL: Not specified | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of drugs and kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of high-dose topotecan and peripheral stem cell transplantation in treating patients with refractory cancer. |
OBJECTIVES: I. Identify a priming schedule of sargramostim (GM-CSF) that reduces the percentage of progenitor cells in cycle at the time of chemotherapy administration in patients with advanced malignancies. II. Determine the maximum tolerated dose and toxic effects of topotecan when administered with sargramostim in these patients. III. Conduct a preliminary assessment of the activity of this topotecan regimen in these patients.~OUTLINE: This is a dose escalation study of topotecan. Patients receive priming with sargramostim (GM-CSF) on days -4 through -2. On day 0, topotecan IV is administered over 30 minutes. Cohorts of 6 patients receive escalating doses of topotecan. The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity (DLT). Sargramostim resumes on day 1 following topotecan, and continues for 5 days or until sufficient hematologic recovery. The next course of topotecan is given 48 hours later. Treatment repeats every 6 weeks for 4 courses. Patients are followed every 3 months for the first year, then every 6 months thereafter.~PROJECTED ACCRUAL: 15-25 patients will be accrued for the duration of 18 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.~PURPOSE: Phase I/II trial to study the effectiveness of topotecan plus sargramostim in treating patients who have advanced cancer. |
OBJECTIVES: I. Determine whether morphine injected at the site of surgery can control pain from surgery.~OUTLINE: This is a prospective, double blind, randomized study. Patients are randomized into 3 groups with 6 patients in each group. Group 1 receives morphine diluted in normal saline (NS), which is administered in the axillary region at the completion of surgery before surgical closure. The area is flooded and the solution is allowed to remain in the wound for 5 minutes. Group 2 (control group) receives NS only, administered in the same fashion as group 1. Group 3 receives morphine subcutaneously in the deltoid area, ipsilateral to the site of surgery, at the beginning of wound closure. Postoperatively, patients self-administer IV fentanyl analgesia through a patient controlled analgesia pump. Comparisons of daily IV fentanyl utilization is done among the three groups. Quality of pain is assessed via visual analog pain scores four times a day at 2, 4, 6, and 24 hours postoperatively.~PROJECTED ACCRUAL: A total of 18 patients will be accrued over a period of 2 years. | RATIONALE: Morphine helps to relieve the pain associated with cancer surgery. Giving morphine in different ways may offer more pain relief.~PURPOSE: This randomized clinical trial is studying how well morphine injected directly into the underarm area works compared with morphine injected into the back of the shoulder in treating pain in patients who have breast cancer and who are undergoing axillary lymph node dissection. |
OBJECTIVES: I. Define the safe and tolerance of an inhaled interleukin-2 (IL-2) administered once or twice a day. II. Determine blood levels of IL-2 and whether there is detectable stimulation of immune cells in patients receiving inhalation IL-2. III. Determine whether there is any shrinkage of pulmonary lesions of patients treated on this study.~OUTLINE: This is a two arm, escalating dose study of interleukin-2 (IL-2). In Arm I patients in cohorts of 3-6 are administered daily inhalations of IL-2 over 15 minutes on Monday through Friday for 4 consecutive weeks. At least 3 patients are treated at each dose level, and all patients in a cohort are observed for at least 2 weeks before escalating to a higher dose in absence of dose limiting toxicity. Escalation stops when maximum tolerated dose (MTD) is determined. In Arm II the initial dose is 25 percent of the MTD determined in Arm I administered by inhalation twice daily on Monday through Friday for 4 weeks. Subsequent patient cohorts receive doses escalated by 33 percent above the previous dose level. Responding patients continue treatment cycles of 4 weeks with 2 weeks of rest until they develop progressive disease or intolerable toxicity. Stable patients may stay on treatment for a maximum of 4 cycles.~PROJECTED ACCRUAL: A minimum of 12-15 and a maximum of 30 patients will be accrued for this study. | RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Giving interleukin-2 in different ways may kill more cancer cells.~PURPOSE: Phase I trial to study the effectiveness of inhaled interleukin-2 in treating patients with metastatic or unresectable cancer. |
OBJECTIVES: I. Determine the maximum tolerated dose of bizelesin in patients with advanced cancer. II. Determine the qualitative and quantitative toxic effects of this therapy in these patients. III. Determine the pharmacokinetics of this therapy in these patients. IV. Determine the recommended dose of this drug for phase II trials. V. Determine the antitumor effects of this therapy in these patients.~OUTLINE: This is a dose-escalation study. Patients receive bizelesin IV on day 1. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bizelesin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.~PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of bizelesin in treating patients who have advanced cancer. |
OBJECTIVES:~Determine whether there is a relationship between pharmacokinetic measurements of paclitaxel and aging.~Determine whether there is a relationship between the toxic effects of paclitaxel and aging.~OUTLINE: Patients are stratified according to age (cohort 1: patients 55 to 64 vs cohort 2: patients 65 to 75 vs cohort 3: patients 75 and over). | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase III trial to study the effectiveness of paclitaxel in treating older patients who have solid tumors. |
OBJECTIVES: I. Determine the effect of varying the dietary intake of soy nuts on plasma levels and urinary excretion of isoflavones. II. Determine the effects of different food composition, along with age and gender of subjects, on plasma levels and urinary excretion of isoflavones.~OUTLINE: This is a two part study. In part I; participants are stratified according to menopausal status. In part II; participants are stratified according to gender and age (under 50 vs. over 50). Part I - Study participants are given 3 different amounts of toasted soy nuts separated by one month intervals. The sequence in which each amount is given is randomized. Blood and urine samples are taken to measure isoflavone levels. Part II - Study participants are given toasted soy nuts, soy milk, and tempeh on separate occasions separated by one month intervals. The sequence of each food is randomized. Blood and urine samples are taken to measure isoflavone levels.~PROJECTED ACCRUAL: 10 women, 5 premenopausal and 5 postmenopausal, will be accrued for part I of the study. 80 subjects, 40 women and 40 men, will be accrued for part II. | RATIONALE: Eating a diet rich in soy foods appears to reduce the risk of some types of cancer. Isoflavones are compounds found in soy food that may prevent the development of cancer.~PURPOSE: Clinical trial to determine the most effective amount and type of soy isoflavones needed in the diets of healthy men and women to prevent cancer. |
OBJECTIVES: I. Determine the dose limiting toxicity and maximum tolerated dose of combination bryostatin 1 and cisplatin chemotherapy in patients with advanced, incurable solid tumors.~OUTLINE: This is a dose-escalation study. The first 4 cohorts of patients receive an escalating dose of cisplatin with a fixed dose of bryostatin 1, followed by 5 cohorts receiving an escalating dose of bryostatin 1 and a fixed dose of cisplatin. In the first course, cisplatin is given as a 2 hour infusion followed by a 24 hour continuous infusion of bryostatin 1. In all subsequent courses bryostatin 1 is given first and cisplatin afterwards. Treatment continues every 21 days in patients with stable or responding disease. Dose escalation proceeds until the maximum tolerated dose (MTD) of the combination chemotherapy is determined. The MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity. After the MTD is determined, an additional 10 patients are treated at this dose level. Patients are followed at 1 month.~PROJECTED ACCRUAL: Approximately 24-30 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of cisplatin plus bryostatin 1 in treating patients who have advanced cancer. |
OBJECTIVES: I. Determine the maximum tolerated dose of irinotecan in combination with raltitrexed in patients with refractory solid tumors. II. Describe and quantify the toxic effects of this combination treatment regimen in a minimally pretreated patient population. III. Determine the pharmacokinetics of this combination treatment regimen. IV. Document any antitumor activity of this combination treatment regimen in this patient population.~OUTLINE: This is a dose escalation study of irinotecan and raltitrexed. Patients receive irinotecan IV over 90 minutes on days 1 and 8 followed by raltitrexed IV over 15 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of irinotecan and raltitrexed until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Additional cohorts receive raltitrexed on day 2 rather than day 1 near the final dose levels of the combination drugs.~PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 1 year. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of irinotecan plus raltitrexed in treating patients who have refractory solid tumors that have not responded to previous therapy. |
OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of bryostatin 1 in combination with cisplatin in patients with advanced malignancy. II. Determine the recommended phase II doses of bryostatin 1 and cisplatin in both a 21 day and 14 day course, based on toxicity, effect on protein kinase C activity, and pharmacokinetics, in this patient population. III. Determine the pharmacokinetics of bryostatin 1 in these patients. IV. Identify any objective tumor responses arising from treatment in these patients.~OUTLINE: This is a dose escalation study of bryostatin 1. Cohorts 1-7: Patients receive cisplatin IV over 1 hour on day 1 of the first course. Subsequent courses repeat every 21 days with bryostatin 1 IV over 24 hours on day 1 and cisplatin IV over 1 hour on day 2 in the absence of disease progression or unacceptable toxicity. Cohorts 8-10: Patients receive cisplatin as in cohorts 1-7. Subsequent courses repeat every 21 days with bryostatin 1 IV over 1 hour followed by cisplatin on day 1. Cohort 11: Patients receive bryostatin 1 and cisplatin as in cohorts 8-10. Cohorts of 3-6 patients receive escalating doses of bryostatin 1 or cisplatin until the maximum tolerated dose (MTD) of is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. The recommended phase II dose (RPTD) is defined as the dose preceding the MTD. After the RPTD is determined for the 21 day schedule, cohorts of patients receive escalating doses of bryostatin and constant doses of cisplatin on a 14 day schedule. The MTD14 and RPTD14 are determined in the same manner as above. Patients are followed for 6 months.~PROJECTED ACCRUAL: A total of 36-72 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of bryostatin 1 plus cisplatin in treating patients who have metastatic or unresectable cancer. |
OBJECTIVES: I. Determine the maximum tolerated doses and sequence of topotecan and ifosfamide that can be administered daily for 3 days on an every 4 week schedule in patients with refractory solid tumors. II. Evaluate toxicity of topotecan and ifosfamide when administered on this schedule in this patient population. III. Evaluate the pharmacokinetics related to sequencing of topotecan and ifosfamide and the more efficacious, less toxic schedule of treatment. IV. Assess the evidence of antineoplastic activity for this combination of agents.~OUTLINE: This is an open label, dose escalation study. Cohorts of 3-6 patients receive ifosfamide at an initial fixed dose plus escalating doses of topotecan by 30 minute infusion daily for 3 successive days. Cycle repeats every 28 days. After topotecan dosage is escalated for a total of 3 dose levels, then ifosfamide dose is escalated by one dose level. The first patient enrolled is treated with ifosfamide followed by topotecan for cycle 1, and for cycle 2 the order of drugs is reversed. The second patient is treated with the same drugs but with topotecan administered before ifosfamide in the first cycle and then reversed in the second cycle. From the third cycle onward, ifosfamide is followed by topotecan, but the first two cycles continue to alternate with each subsequent patient entered. Filgrastim (granulocyte colony-stimulating factor; G-CSF) is given for all cycles on days 5-12 or until the absolute granulocyte count has reached its nadir and recovered. If there is no dose limiting toxicity (DLT) in a cohort, new patients are entered at the next highest dose level. If 1 of 3 patients at any level experiences DLT, an additional 3 patients are treated at that level before proceeding to a higher level. If 2 or more patients experience DLT at any dose level, the level immediately preceding that level is defined as the maximum tolerated dose (MTD). Three more patients are treated at the MTD to ensure that no DLT is experienced at that level. After MTD is identified, 10 additional patients are accrued at that level. Patients with minor response, stable disease, or symptomatic or marker improvement may continue on treatment for up to 6 cycles. After 6 cycles, continuation on treatment is at the investigator's discretion.~PROJECTED ACCRUAL: There will be a maximum of 24 patients accrued into this study over 8 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of chemotherapy with ifosfamide and topotecan in treating patients with refractory solid tumors. |
OBJECTIVES:~I. Determine the maximum tolerated dose of carboxyamidotriazole (CAI) in combination with ketoconazole in patients with advanced malignancies.~II. Evaluate the toxic effects, safety, and efficacy of CAI in combination with ketoconazole.~III. Determine the modulatory effects of ketoconazole on the pharmacokinetic profile of CAI.~IV. Determine a pharmacodynamic model for CAI and ketoconazole with respect to potential gastrointestinal, hematologic, and neurotoxicities.~OUTLINE: This is a dose escalation study.~Patients receive oral carboxyamidotriazole (CAI) as a test dose on day 1. Patients receive oral ketoconazole on day 7, followed by CAI plus ketoconazole on day 8. CAI and ketoconazole are administered in combination on day 1 and days 3-28 of the first course. Ketoconazole is administered alone on day 2 of the first course. Subsequent courses begin at 28 day intervals in the absence of disease progression or unacceptable toxic effects. Cohorts of 3 patients are evaluated at each dose level prior to dose escalation. If one of three patients within a cohort experiences dose limiting toxicity (DLT), that dose level is expanded to incorporate six patients. If two or more patients experience DLT, the next lower dose is declared to be the maximum tolerated dose. | Phase I trial to study the effectiveness of carboxyamidotriazole and ketoconazole in treating patients with advanced cancers. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. |
OBJECTIVES: I. Determine the maximum tolerated dose and toxicity of oral fenretinide in patients with solid malignant tumors. II. Determine the pharmacokinetics of fenretinide and its metabolites. III. Determine the preliminary antitumor activity of fenretinide in this patient population. IV. Determine the recommended phase II starting dose of fenretinide. V. Determine whether fenretinide induces apoptosis in clinical specimens.~OUTLINE: This is a dose escalation study. Patients receive oral fenretinide once daily on days 1, 8 and 9 and three times a day on days 2-7. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Treatment continues for up to 6 months following complete remission. Accessible tumors are biopsied on day 8. Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.~PROJECTED ACCRUAL: Approximately 21 patients will be accrued for this study within 6-9 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of fenretinide in treating patients who have solid tumors. |
PRIMARY OBJECTIVES:~I. Determine the optimal dose of etanidazole derivative EF5 that is safely tolerated and provides optimal signal-to-noise ratio in patients with solid tumors.~II. Determine the toxic effects of EF5 in this patient population. III. Determine the pharmacokinetics of EF5 in this patient population. IV. Determine the dose of EF5 that provides a mean signal-to-noise ratio (maximum binding in anoxia to minimum binding) of 75.~V. Determine the relationship between tumor oxygenation by EF5 binding and needle electrode measurements.~VI. Compare the levels of EF5 binding in regions of low and high blood flow.~OUTLINE: This is a dose-escalation study.~Patients receive etanidazole derivative EF5 IV over 1-2 hours beginning approximately 24 hours prior to surgery. Tumors are then resected or biopsied after Eppendorf needle electrode measurements.~Cohorts of 6 patients receive escalating doses of EF5 until the maximum tolerated dose (MTD) or optimal dose is determined. The MTD is defined as the dose preceding that at which 2 or more patients experience dose-limiting toxicity. The optimal dose is defined as the dose level at or below the MTD and results in a signal-to-noise ratio of 75 or greater. Thirty additional patients are treated at the optimal dose.~Patients are followed at 30-45 days post EF5 infusion.~PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study. | Diagnostic procedures using the drug EF5 to detect the presence of oxygen in tumor cells may help to plan effective treatment for solid tumors. This phase I trial is studying how well EF5 works in detecting the presence of oxygen in tumor cells in patients with solid tumors that can be biopsied or removed by surgery |
OBJECTIVES:~I. Determine the toxicity profile and maximum tolerated dose (MTD) of intravenous interleukin-12 (IL-12) administered biweekly for 6-18 weeks in the presence and absence of a test dose in patients with metastatic or unresectable malignancies.~II. Determine the optimal timing for administration of an IL-12 test dose, based on its impact on secondary biologic parameters in these patients.~III. Determine the antitumor effects of IL-12 administered according to this schedule, with and without a test dose, in these patients.~IV. Determine the effect of a test dose on toxicity profile, MTD, tumor response and various biologic phenomena in serum, and, where possible, tumor and liver in these patients.~OUTLINE: This is a 3-part dose escalation study.~In Part A, patients receive intravenous interleukin-12 (IL-12) twice a week for 6 weeks. Courses are repeated until patients achieve a complete response or there is disease progression. Dose escalation of IL-12 continues in cohorts of 3-6 patients until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose below that at which 2 of 6 patients experience dose limiting toxicity (DLT).~In Part B, patients receive a single test dose of IL-12 administered intravenously at a 1, 2, or 3 week interval prior to starting the multidose twice a week regimen as in Part A. Cohorts of 4 patients will receive IL-12 at the MTD obtained in Part A.~In Part C, patients receive IL-12 at one dose level above the MTD obtained in Part A using the optimal schedule for the test dose determined in Part B. Dose escalation continues in cohorts of 3-6 patients until the MTD is determined. The MTD is defined as the dose below that at which 2 of 6 patients experience DLT. Patients may continue to receive IL-12 until they have no measurable disease or until disease progression. | Phase I trial to study the effectiveness of interleukin-12 in treating patients who have advanced cancer. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. |
OBJECTIVES: I. Determine the maximum tolerated dose of T138067 sodium that can be given to patients with advanced refractory cancer on a 28-day schedule and establish a dose for further study. II. Evaluate the safety and dose limiting toxicity of T138067 sodium in these patients. III. Determine the pharmacokinetic parameters after a single intravenous dose of this agent in these patients. IV. Obtain safety data and preliminary efficacy information after repetition of single doses of T138067 sodium in these patients.~OUTLINE: This is an open label, dose escalation study. Patients receive T138067 sodium by IV over 3 hours. Patients may be retreated every 4 weeks for up to 6 courses (6 months total) in the absence of disease progression or dose limiting toxicity (DLT). At least 3 patients are treated at each dose level in the absence of DLT. The maximum tolerated dose is defined as the dose level where 2 of 3-6 patients experience DLT.~PROJECTED ACCRUAL: Approximately 3-24 patients will be accrued into this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of T138067 sodium in treating patients with advanced refractory cancer. |
OBJECTIVES: I. Determine the feasibility of administering multiple courses of chemotherapy without excessive dose modification or treatment delay in patients with previously untreated ovarian epithelial carcinoma or primary peritoneal carcinoma. II. Determine the response rate (in patients with measurable disease) and progression-free interval in these patients receiving this treatment.~OUTLINE: This is a feasibility study. On day 1, patients receive paclitaxel as a 3 hour continuous IV infusion followed by carboplatin as a 30 minute infusion. Gemcitabine is administered by continuous infusion over 30 minutes on day 1 following carboplatin and on day 8. In the absence of disease progression or unacceptable toxicity, courses repeat every 21 days for a maximum of 8 courses. Patients are followed every 3 months for 2 years, every 6 months for the next 3 years, and annually thereafter.~PROJECTED ACCRUAL: A total of 15-45 patients will be accrued for this study within approximately 2 years. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients with previously untreated stage III or stage IV ovarian or primary peritoneal cancer. |
OBJECTIVES: I. Determine the maximum tolerated dose of GPX-100 in outpatients with incurable, solid tumors who are not candidates for effective systemic therapy. II. Evaluate and quantify the toxicity of GPX-100 in this patient population. III. Identify any changes in disease status in this patient population.~OUTLINE: This is an open label, multicenter, dose escalation study. Patients receive GPX-100 IV once every 3 weeks. Patients receive 2 courses of treatment in the absence of disease progression or dose limiting toxicity. Treatment may continue for up to 6 courses (4 courses with prior doxorubicin) in patients with responding or non-progressing disease. One patient is entered at each of the first 3 dose levels. Cohorts of 3-6 patients are entered at subsequent dose levels. The maximum tolerated dose of GPX-100 is defined as the dose at which no more than 2 instances of dose limiting toxicity are observed in 6 patients.~PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of GPX-100 in treating patients who have solid tumors. |
OBJECTIVES:~I. Assess the safety and maximum tolerated dose of recombinant human interleukin-12 (rhIL-12) administered by intraperitoneal infusion in patients with chemotherapy refractory advanced ovarian cancer and other diffuse abdominal carcinomatosis.~II. Determine the immunopharmacologic profile of rhIL-12 in this patient population.~III. Evaluate the biologic response in selected patients to rhIL-12 administered through intraperitoneal infusions.~OUTLINE: This is a dose escalation, multicenter study.~Cohorts of 3-6 patients each receive escalating doses of intraperitoneal recombinant human interleukin-12 (rhIL-12) administered weekly for 9 weeks. If a patient tolerates rhIL-12 and shows evidence of objective response or stable disease, patient may receive up to 9 additional weeks of treatment. Treatment continues in the absence of unacceptable toxicity or disease progression. Dose escalation continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which no more than 1 of 6 patients experiences dose limiting toxicity.~All patients are followed for survival. | Phase I trial to study the effectiveness of interleukin-12 in treating patients with refractory ovarian or abdominal cancers. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a persons's white blood cells to kill cancer cells. |
Recurrent or Stage IV Lung Cancer patients receive gradually escalating doses of intravenous Antineoplaston therapy (Atengenal + Astugenal) until the maximum tolerated dose is reached. Treatment continues up to 12 months in the absence of disease progression or unacceptable toxicity.~OBJECTIVES:~To determine the efficacy of Antineoplaston therapy in patients with Recurrent or Stage IV Lung Cancer, as measured by an objective response to therapy (complete response, partial response or stable disease).~To determine the safety and tolerance of Antineoplaston therapy in patients with Recurrent or Stage IV Lung Cancer.~To determine objective response, tumor size is measured utilizing MRI scans, which are performed every 8 weeks for the first two years, every 3 months for the third and fourth years, every 6 months for the 5th and sixth years, and annually thereafter. | Current therapies for Recurrent or Stage IV Lung Cancer provide very limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of Recurrent or Stage IV Lung Cancer.~PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on patients with Recurrent or Stage IV Lung Cancer. |
Cancer of Unknown Primary Origin patients receive gradually escalating doses of intravenous Antineoplaston therapy (Atengenal + Astugenal) until the maximum tolerated dose is reached. Treatment continues up to 12 months in the absence of disease progression or unacceptable toxicity.~OBJECTIVES:~To determine the efficacy of Antineoplaston therapy in patients with Cancer of Unknown Primary Origin, as measured by an objective response to therapy (complete response, partial response or stable disease).~To determine the safety and tolerance of Antineoplaston therapy in patients with Cancer of Unknown Primary Origin.~To determine objective response, tumor size is measured utilizing MRI scans, which are performed every 8 weeks for the first two years, every 3 months for the third and fourth years, every 6 months for the 5th and sixth years, and annually thereafter. | Current therapies for Cancer of Unknown Primary Origin provide very limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of Cancer of Unknown Primary Origin.~PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on patients with Cancer of Unknown Primary Origin. |
OBJECTIVES: I. Determine the qualitative and quantitative toxicities of intraperitoneal aminocamptothecin colloidal dispersion administered every 28 days in 6 applications over a 12 day period in patients with advanced cancer confined to the peritoneal cavity. II. Determine the maximum tolerated dose of aminocamptothecin colloidal dispersion on this novel schedule in this patient population. III. Obtain pharmacological and biochemical data as potential predictors of responses and/or drug toxicities in these patients. IV. Document the presence and degree of antitumor activity of this regimen in this patient population.~OUTLINE: This is a dose escalation study. Patients receive intraperitoneal aminocamptothecin colloidal dispersion (9-AC) over 30-60 minutes in 6 applications over a 12 day period (days 1, 3, 5, 8, 10, and 12). Courses are repeated every 28 days. Treatment continues for 4-6 courses in the absence of unacceptable toxic effects or disease progression. The dose of 9-AC is escalated in cohorts of 3-6 patients until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity. Patients are followed until death.~PROJECTED ACCRUAL: Approximately 15-20 patients will be accrued for this study within 18 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of aminocamptothecin in treating patients with advanced cancer of the peritoneal cavity. |
OBJECTIVES: I. Determine the maximum tolerated dose of weekly paclitaxel following amifostine in patients with recurrent or refractory solid tumors. II. Assess tumor response rate and survival in these patients.~OUTLINE: This is a dose escalation study of paclitaxel. Patients receive amifostine IV over 5 minutes or less on day 0, followed by paclitaxel IV over 1 hour once a week for 6 weeks followed by 2 weeks of rest. Patients with complete or partial response may receive additional courses of therapy. Cohorts of 3-5 patients each receive increasing doses of paclitaxel. The maximum tolerated dose is defined as the dose level prior to the cohort at which 1 of 3-5 patients experience dose limiting toxicity.~PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy.~PURPOSE: Phase I trial to study the effectiveness of paclitaxel plus chemoprotection with amifostine in treating patients with recurrent or refractory solid tumors. |
OBJECTIVES: I. Determine whether theophylline will improve the dyspnea rating of patients with cancer who are short of breath and have evidence of respiratory muscle weakness. II. Determine whether this drug will improve the ability to perform daily activities in this group of patients. III. Determine whether this drug will improve objective measures of lung function (e.g., FEV-1, FVC) and maximum inspiratory pressure in these patients. IV. Determine whether the serum theophylline level is related to the magnitude of the effect that is observed in this patient population. V. Determine whether this drug will improve a global rating of quality of life in this patient group.~OUTLINE: This is a randomized, double blind, multicenter study. Patients are stratified according to those who can complete a 6 minute walking test versus those who cannot. Patients receive either oral theophylline or placebo once daily for 3 days. In the absence of dose limiting toxicity (DLT), patients receive an increased dose for an additional 4 days. In the presence of DLT, patients receive a decreased dose or treatment is stopped. Following completion of the 7 day study period, patients may be given the option to continue on active drug or placebo for 1 additional month unless toxic side effects develop. Quality of life is assessed on days 1 and 8 and at the end of the additional 1 month period.~PROJECTED ACCRUAL: A total of 60 patients (30 in each arm) will be accrued for this study. | RATIONALE: Theophylline may help to relieve shortness of breath in patients who have cancer. It is not yet known whether theophylline is more effective than no further treatment for shortness of breath.~PURPOSE: Randomized phase III trial to determine the effectiveness of theophylline in treating shortness of breath in patients who have cancer. |
OBJECTIVES: I. Evaluate the effectiveness of daily oral pilocarpine versus placebo in relieving dry mouth due to the ongoing use of an opioid for cancer related pain at 2 weeks by comparing proportion of patients with at least one response during the 2 week period, time of first response, and duration of first response. II. Evaluate the adverse effects of pilocarpine in these patients. III. Evaluate whether constipation, sedation, poor appetite, and nausea are ameliorated by pilocarpine in these patients. IV. Evaluate the effect of pilocarpine on quality of life of this patient group. V. Determine the timing and duration of the effect of pilocarpine in this patient population.~OUTLINE: This is a randomized, double-blind, multicenter study. Patients receive either oral pilocarpine four times daily (arm I) or oral placebo four times daily (arm II) for 4 weeks. At the end of the 4 weeks, all patients are given the option to receive oral pilocarpine. Quality of life is assessed 2 days prior to randomization, after 2 weeks of treatment, and after 4 weeks of treatment.~PROJECTED ACCRUAL: There will be 60 patients accrued into this study within 18 months. | RATIONALE: Pilocarpine may help to relieve dry mouth in patients receiving opioids for cancer therapy. It is not yet known whether pilocarpine is more effective than no further treatment for this condition.~PURPOSE: Randomized phase III trial to determine the effectiveness of pilocarpine in treating patients who have dry mouth caused by opioids. |
OBJECTIVES: I. Determine the maximum tolerated dose of SarCNU in patients with advanced solid malignancies. II. Determine the toxic effects of SarCNU in these patients. III. Characterize the pharmacokinetic profile of this regimen in these patients. IV. Determine any evidence of antineoplastic activity of this regimen in these patients.~OUTLINE: This is a dose-escalation study. Patients receive oral SarCNU on days 1, 5, and 9. Treatment continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SarCNU until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the MTD.~PROJECTED ACCRUAL: Approximately 12-36 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of chemotherapy using sarCNU in patients who have advanced solid tumors. |
OBJECTIVES: I. Determine the maximum tolerated dose, dose limiting toxicity, recommended phase II dose, and safety of BMS-184476 in patients with advanced solid tumors. II. Determine the pharmacokinetic profile of BMS-184476 and its metabolites in these patients. III. Determine preliminary evidence of antitumor activity of BMS-184476 in these patients.~OUTLINE: This is an open label, dose escalation study. Patients receive BMS-184476 IV over 1 hour. Treatment is repeated every 21 days in the absence of disease progression or unacceptable toxicity. In the second part of the study, patients receive BMS-184476 IV over 1 hour weekly. Cohorts of 3-6 patients are treated at escalating doses of BMS-184476. The maximum tolerated dose is defined as the dose at which fewer than 2 of 6 patients experience dose limiting toxicity. Patients are followed every 4 weeks until toxicity is resolved.~PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 12-18 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of BMS-184476 in treating patients who have advanced solid tumors. |
OBJECTIVES: I. Determine the toxic effects and maximum tolerated dose (MTD) of LY231514 in patients with metastatic or locally advanced solid tumors and varying degrees of renal function. II. Determine the recommended dose for LY231514 in this patient population. III. Examine the effects of renal dysfunction on the pharmacokinetics of LY231514 in this patient population. IV. Examine the relationship between impaired renal function, drug exposure, and drug effects in these patients. V. Gather data for development of a LY231514 dosing nomogram based on renal function. VI. Collect preliminary data regarding antitumor effects of LY231514 in this patient population.~OUTLINE: This is an open label, dose escalation study. Patients are stratified according to renal function. Group 1 consists of patients with normal renal function, and groups 2, 3, and 4 consist of patients with mild, moderate, and severe renal impairment. All patients receive LY231514 IV over 10 minutes every 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients are treated with escalating doses of LY231514 within each treatment group. If dose limiting toxicity (DLT) is observed in 1 of 3 patients at a given dose level, then 3 additional patients are studied. The maximum tolerated dose is defined as the dose level at which less than 2 of 6 patients experience DLT. Patients are followed until death.~PROJECTED ACCRUAL: Up to 50 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemotherapy drugs may have different effects in patients with different degrees of kidney function.~PURPOSE: Phase I trial to study the effectiveness of LY231514 in treating patients who have locally advanced or metastatic solid tumors and varying degrees of kidney function. |
OBJECTIVES:~Determine the maximum tolerated dose and dose limiting toxicities of tipifarnib in combination with gemcitabine in patients with advanced cancer.~Investigate potential pharmacokinetic interactions between tipifarnib and gemcitabine in these patients.~Determine the efficacy of this regimen in patients with measurable or evaluable disease.~Evaluate the quality of life of these patients.~OUTLINE: This is a dose-escalation study of tipifarnib.~Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and oral tipifarnib every 12 hours beginning on day 2. Treatment continues every 4 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients each receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose at which fewer than one third of the patients experience dose limiting toxicity.~Quality of life is assessed before treatment, on day 22 of each course, and at the end of treatment.~PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.~PURPOSE: Phase I trial to study the effectiveness of combining R115777 with gemcitabine in treating patients with advanced cancer. |
OBJECTIVES: I. Determine the safety, tolerability, maximum tolerated dose, and dose limiting toxicity of temozolomide in patients with advanced solid malignancies. II. Characterize the single- and multiple-dose pharmacokinetics of temozolomide following oral administration in these patients. III. Determine antitumor activity of temozolomide in these patients.~OUTLINE: This is an open label, dose escalation study. Patients receive oral temozolomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients are treated at escalating doses of temozolomide. The maximum tolerated dose is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicity (DLT) during courses 1 or 2, with at least 2 patients experiencing DLT at the next higher dose level.~PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of temozolomide in treating patients who have advanced solid tumors. |
OBJECTIVES: I. Determine the maximum tolerated dose of LY231514 followed by irinotecan in patients with metastatic cancer. II. Determine the quantitative and qualitative toxicity of LY231514 in combination with irinotecan in these patients. III. Assess plasma pharmacokinetics in these patients treated with this regimen. IV. Document any antitumor activity of this regimen in these patients.~OUTLINE: This is a dose escalation study. Patients receive LY231514 IV over 10 minutes followed by irinotecan IV over 90 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression and unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of LY231514 and irinotecan. If escalation of one drug in the combination results in unacceptable dose limiting toxicity (DLT), the drug is not escalated further. Instead, the dose of that drug is decreased to its safe dose, and the second drug is escalated until unacceptable DLT results. If DLT occurs in 2 of up to 6 patients at any level, dose escalation is stopped. The maximum tolerated dose is defined as the highest dose at which fewer than 2 of 6 patients experience DLT during courses 1 or 2.~PROJECTED ACCRUAL: Up to 42 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy with pemetrexed disodium and irinotecan in treating patients who have metastatic solid tumors. |
OBJECTIVES: I. Determine the intolerable dose level of intoplicine in patients with locally advanced or metastatic cancer. II. Determine recommended phase II dose of intoplicine in these patients. III. Determine the principal and dose limiting toxicities of intoplicine in these patients, and determine the duration and reversibility of the toxicities. IV. Determine the magnitude of plasma concentrations that are achieved and maintained on this regimen and relate this parameter to toxicity outcome and antitumor activity. V. Determine preliminary evidence of antitumor activity of intoplicine in these patients.~OUTLINE: This is a dose escalation study. The first 3 patients receive intoplicine IV by continuous infusion for 5 days. Treatment is repeated every 28 days in the absence of disease progression or unacceptable toxicity. Subsequent cohorts of 3-6 patients receive escalating doses of intoplicine, first by increasing the number of days that the drug is infused to 10, 15, and 21, then by increasing the dosage and keeping the infusion time constant at 21 days. The intolerable dose level is defined as the lowest dose at which at least 2 of 3 or 6 patients experience dose limiting toxicity during course 1 or 2.~PROJECTED ACCRUAL: A total of 20-35 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of intoplicine in treating patients who have advanced or metastatic solid tumors. |
OBJECTIVES: I. Determine the efficacy and toxic effects of thalidomide and cyclophosphamide in patients with recurrent or refractory pediatric malignancies.~OUTLINE: Patients receive oral thalidomide 4 times daily. Cyclophosphamide is administered IV over 1 hour once every 4 weeks, beginning on the same day as thalidomide. Treatment continues in the absence of unacceptable toxicity or disease progression. Tumor response is assessed every 3 months.~PROJECTED ACCRUAL: A total of 45-80 patients will be accrued for this study within 2 years. | RATIONALE: Thalidomide may kill tumor cells by stopping the growth of new blood vessels to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with chemotherapy may kill more tumor cells.~PURPOSE: Phase II trial to study the effectiveness of combining thalidomide and cyclophosphamide in treating children who have recurrent or refractory childhood cancers. |
OBJECTIVES: I. Determine the maximum tolerated dose of combretastatin A4 phosphate when administered at single doses every 21 days in patients with advanced solid tumors. II. Determine both the toxicity and dose limiting toxicity of this regimen in these patients. III. Determine the plasma and urine pharmacokinetics of combretastatin A4 and combretastatin A4 phosphate. IV. Gather preliminary data regarding possible antitumor effects in those patients with measurable disease.~OUTLINE: This is an open label, dose escalation study. Patients receive combretastatin A4 phosphate IV over 10-60 minutes. Treatment repeats every 3 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of combretastatin A4 phosphate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity. Patients are followed at 3 weeks.~PROJECTED ACCRUAL: A maximum of 21 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of combretastatin A4 phosphate in treating patients who have advanced solid tumors that have not responded to previous therapy. |
OBJECTIVES: I. Determine the maximum tolerated dose of SR-45023A in patients with locally advanced or metastatic solid tumors that are refractory or for which no standard therapy exists. II. Determine the quantitative toxic effects of SR-45023A in these patients. III. Assess the pharmacokinetic profile of SR-45023A in these patients. IV. Identify the antitumor activity of SR-45023A in these patients.~OUTLINE: This is a dose escalation study. Patients receive oral SR-45023A twice daily for 14 days, followed by 7 days rest. On day 14 of course 1, patients receive only one dose of therapy due to pharmacokinetic sampling. Treatment continues every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SR-45023A until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed until death.~PROJECTED ACCRUAL: Up to 30 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of SR-45023A in treating patients who have advanced solid tumors. |
OBJECTIVES: I. Determine the maximum tolerated dose and toxic effects of irinotecan and oral capecitabine in patients with gastrointestinal or other solid tumors. II. Characterize the relationship at the recommended phase II dose between thymidine synthase and thymidine phosphorylase expression and tumor response and/or toxic effects in these patients.~OUTLINE: This is a dose escalation study. Patients receive oral capecitabine twice daily every twelve hours for 14 days, and IV irinotecan over 30 minutes once every 3 weeks beginning on day 1. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity. The dose of capecitabine and irinotecan is escalated in cohorts of 3-6 patients until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity.~PROJECTED ACCRUAL: Approximately 25-30 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of irinotecan and capecitabine in treating patients who have solid tumors that have not responded to previous treatment. |
OBJECTIVES: I. Assess the effect of paclitaxel and carboplatin with or without SCH 58500 on progression free survival, overall survival, safety, response, and CA-125 levels in patients with newly diagnosed stage III ovarian epithelial or primary peritoneal cancer.~OUTLINE: This is a randomized, open label, multicenter study. Patients receive treatment of IV paclitaxel and IV carboplatin. Patients are randomized to one of two treatment groups: Arm I: Patients receive IV paclitaxel over 3 hours, immediately followed by IV carboplatin, on day 1. Courses are repeated every 21 days. Arm II: Patients receive IV paclitaxel over 3 hours, immediately followed by IV carboplatin, on day 1. Patients receive intraperitoneal SCH 58500 on days 1-5. Courses are repeated every 21 days. Patients are followed every 6 weeks for 36 months, then every 3 months for 2 years, and then every 6 months until disease progression.~PROJECTED ACCRUAL: A total of 360 patients (180 per treatment arm) will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with gene therapy using SCH-58500 may kill more tumor cells.~PURPOSE: Randomized phase II/III trial to determine the effectiveness of paclitaxel plus carboplatin with or without SCH-58500 in treating patients who have newly diagnosed stage III ovarian or stage III primary peritoneal cancer with residual disease following surgery to remove the tumor. |
OBJECTIVES:~Determine the maximum tolerated dose of MG98 in patients with advanced solid tumors.~Assess the safety, toxicity, and pharmacokinetics of this treatment regimen in this patient population.~Evaluate the effectiveness of this treatment regimen in these patients.~OUTLINE: This is a dose escalation, multicenter study.~Patients receive MG98 IV over 2 hours twice weekly for 3 weeks. Courses are repeated every 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.~The dose of MG98 is escalated in cohorts of 1-6 patients until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity.~Patients are followed at week 4, then at least every 3 months until relapse of disease.~PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 10-12 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of MG98 in treating patients who have advanced solid tumors. |
OBJECTIVES: I. Determine the efficacy of supplemental oral glutamine in reducing the severity and duration of mucositis in children undergoing stem cell transplantation. II. Determine the safety of this regimen in these patients. III. Determine serum glutamine levels achieved during this regimen in these patients.~OUTLINE: This is a randomized, double blind, multicenter study. Patients are stratified according to inclusion of total body irradiation in the conditioning regimen (yes vs no). Patients receive either oral glutamine or oral placebo (glycine) twice a day beginning on the day of admission for the stem cell transplant and continuing for 28 days or until hospital discharge, whichever is first.~PROJECTED ACCRUAL: A total of 120 patients (60 per arm) will be accrued for this study within 2 years. | RATIONALE: Glutamine may be able to decrease inflammation of the mouth and digestive system in children who are undergoing stem cell transplantation.~PURPOSE: Randomized double-blinded phase II trial to study the effectiveness of glutamine in reducing inflammation of the mouth and digestive system in children who are undergoing peripheral stem cell transplantation. |
OBJECTIVES: I. Determine the maximum tolerated dose of melphalan and thiopeta in patients with recurrent or refractory solid tumors. II. Evaluate the overall survival and response rate in these patients.~OUTLINE: This is a dose escalation study. Patients receive cyclophosphamide IV over 1 hour on day 1 and paclitaxel IV over 4 or 24 hours on day 2, followed by daily filgrastim (G-CSF) subcutaneously beginning on day 3 and continuing through day 7 or until WBCs are greater than 100,000 cells/mm3. Peripheral blood stem cells (PBSC) or autologous bone marrow is collected on days 5-7. At 30-50 days following mobilization, patients receive melphalan IV over 15-60 minutes on days -5 and -4 and thiotepa IV over 2 hours on days -3 and -2, followed by autologous bone marrow transplantation or PBSC infusion on day 0. Sequential dose escalation of melphalan is followed by sequential dose escalation of thiotepa. Dose escalation in cohorts of 5 patients each continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 4, 3 of 7, 4 of 11, or 5 of 15 patients experience dose limiting toxicity. Patients are followed at 60 days and at 12 months.~PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of melphalan and thiotepa plus bone marrow or peripheral stem cell transplantation in treating patients who have recurrent or refractory solid tumors. |
OBJECTIVES:~Determine the maximum tolerated doses of gemcitabine, fluorouracil-uracil (UFT), and leucovorin calcium in patients with advanced refractory cancer.~Assess the toxicity of this combination regimen in this patient population.~Evaluate this regimen in terms of response rate, response duration, and overall survival in these patients.~OUTLINE: This is a dose escalation study of gemcitabine and fluorouracil-uracil.~Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Patients receive oral leucovorin calcium immediately followed by oral fluorouracil-uracil (UFT) three times a day on days 1-21. Courses are repeated every 28 days. Treatment continues in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of gemcitabine and UFT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.~PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combining gemcitabine, fluorouracil-uracil and leucovorin in treating patients who have advanced cancer that has not responded to previous therapy. |
OBJECTIVES:~Determine complete response rate in post-hematopoietic stem cell transplant patients with severe veno-occlusive disease of the liver treated with defibrotide.~Determine the minimal effective dose of this drug in these patients.~Assess toxicity and adverse side effects of this drug in these patients.~OUTLINE: This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide.~Arm I: On days 2-14, patients receive a lower dose of defibrotide IV over 2 hours every 6 hours.~Arm II: On days 2-14, patients receive a higher dose of defibrotide IV over 2 hours every 6 hours.~In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.~PROJECTED ACCRUAL: A total of 140 patients (70 per treatment arm) will be accrued for this study. | RATIONALE: Giving defibrotide may be an effective treatment for liver damage that may result following peripheral stem cell transplantation.~PURPOSE: This randomized phase II trial is studying defibrotide to see how well it works in treating patients with severe liver disease after undergoing peripheral stem cell transplantation. |
OBJECTIVES:~Determine the maximum tolerated dose for a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), in patients with advanced malignancies.~Determine the toxic effects and dose-limiting toxicity of AAG in this patient population.~Determine the safe dose of AAG for a Phase II study.~Measure the pharmacokinetic and pharmacodynamic profiles of AAG in these patients.~Assess time to tumor progression and any antitumor activity in patients treated with AAG.~OUTLINE: This is a dose-escalation study.~Patients receive a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), IV over 15-30 minutes every week. Treatment continues in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.~Patients are followed at 4 weeks.~PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: This phase I trial is studying the side effects and best dose of a geldanamycin analogue in treating patients with advanced cancer. |
OBJECTIVES: I. Determine the safety and tolerability of VX-853 in combination with doxorubicin HCl liposome in patients with relapsed or incurable solid tumors. II. Obtain pharmacokinetic profiles for various dosages of VX-853 administered in combination with doxorubicin HCl liposome. III. Achieve whole blood concentrations of VX-853 in the predicted therapeutically effective range and characterize the pharmacokinetics at these doses. IV. Document antitumor effects of VX-853 in combination with doxorubicin HCl liposome in these patients.~OUTLINE: This is a dose escalation study of VX-853. Patients receive VX-853 orally every 8 hours on days 1-3 and doxorubicin HCL liposome IV over approximately 15 minutes beginning 26 hours after starting VX-853. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of VX-853 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose limiting toxicity.~PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within approximately 18 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I/II trial to study the effectiveness of VX-853 in treating patients who have solid tumors who are receiving liposomal doxorubicin. |
OBJECTIVES: I. Determine the maximum tolerated dose of SR-45023A in patients with locally advanced or metastatic solid tumors. II. Determine the quantitative and qualitative toxic effects of SR-45023A in these patients. III. Assess the plasma and urine pharmacokinetics of SR-45023A and relate these to drug effects, if possible, in these patients. IV. Determine any preliminary antitumor activity of SR-45023A in these patients.~OUTLINE: This is a dose escalation study. Patients receive oral SR-45023A weekly. Treatment continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SR-45023A until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed for up to 1 month.~PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of SR-45023A in treating patients who have locally advanced or metastatic solid tumors that have not responded to previous treatment. |
OBJECTIVES:~Determine the activity of docetaxel in women with platinum resistant, refractory ovarian epithelial or primary peritoneal serous cancer.~OUTLINE: Patients receive docetaxel IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive a minimum of 6 courses of therapy, including 2 courses beyond CR.~PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for this study within 2 years. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase II trial to study the effectiveness of docetaxel in treating women who have ovarian epithelial cancer or primary peritoneal cancer that has not responded to previous treatment. |
OBJECTIVES: I. Determine the toxicity and maximum tolerated dose of gemcitabine and cisplatin in patients with metastatic or recurrent nonhematologic malignancies.~OUTLINE: This is a dose escalation study of gemcitabine. Patients receive gemcitabine IV on days 1 and 8, followed immediately by cisplatin IV over 2 hours on day 8. Courses repeat every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-5 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 5 patients experience dose limiting toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.~PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for this study within 18 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of gemcitabine and cisplatin in treating patients who have metastatic or recurrent solid tumors. |
OBJECTIVES:~Determine the maximum tolerated dose of gemcitabine when given concurrently with bryostatin 1 to patients with advanced refractory cancer.~Access the pattern of toxicity of this drug regimen in this patient population.~Determine the objective response rate, duration of response, and overall survival in patients treated with this drug regimen.~Determine the influence of bryostatin 1 on the pharmacokinetics of gemcitabine.~OUTLINE: This is a dose escalation study.~Patients receive gemcitabine IV over 30 minutes, immediately followed by bryostatin 1 IV over 24 hours, weekly for 3 weeks (days 1, 8, and 15). Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.~Cohorts of 3-6 patients receive escalating doses of gemcitabine and bryostatin 1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxic effects.~PROJECTED ACCRUAL: Approximately 2-3 patients per month will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of bryostatin 1 plus gemcitabine in treating patients who have advanced cancer that has not responded to previous treatment. |
OBJECTIVES:~Determine the maximum tolerated dose of oxaliplatin and paclitaxel in patients with metastatic or unresectable cancer.~Determine the qualitative and quantitative toxicities of this regimen in these patients.~Determine the therapeutic response to this regimen in these patients.~Determine the relationship between the pharmacokinetics of this regimen and toxicity and response in these patients.~Determine the effects of oxaliplatin on peripheral blood cells and correlate this to pharmacokinetics, toxicity, and response in these patients.~OUTLINE: This is a dose escalation study.~Patients receive oxaliplatin IV over 2 hours followed by paclitaxel IV over 1 hour weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of oxaliplatin and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicity.~PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 12-18 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of oxaliplatin and paclitaxel in treating patients who have metastatic or unresectable cancer. |
OBJECTIVES: I. Determine the effects of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) in patients with solid tumors by evaluating the safety and tolerability, maximum tolerated dose (MTD) and recommended dose for Phase II studies, pharmacokinetics, and tumor response.~OUTLINE: This is a dose escalation study. Patients receive 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) IV over 2 hours on days 1-5. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of 3-AP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed for 4 weeks or until recovered.~PROJECTED ACCRUAL: Approximately 21 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in treating patients who have solid tumors that have not responded to previous treatment. |
OBJECTIVES: I. Determine the maximum tolerated dose and safety of intratumoral live, genetically modified Salmonella typhimurium (VNP20009) in patients with refractory, superficial solid tumors. II. Determine the efficacy of VNP20009 in these patients.~OUTLINE: This is a dose-escalation study. Patients receive intratumorally injected live, genetically modified Salmonella typhimurium (VNP20009) on day 0. The tumor is biopsied on day 14. Cohorts of 3-6 patients receive escalating doses of VNP20009 until the maximum tolerated dose (MTD) or the optimal biologic dose (OBD) is determined. The MTD is defined as the highest dose in which no more than 1 patient in a cohort of 6 experiences dose-limiting toxicity (DLT). The OBD is defined as the dose at which 3-6 patients of a cohort have greater than 10 million colony-forming units of VNP20009 per gram in the tumor biopsy. Prior to reaching the OBD, 2 to 3 additional patients may be entered at a previous dose level shown to be safe to undergo biopsy of the injected lesion between days 5 and 8. Patients are assessed for systemic tumor response 4-5 weeks after treatment. If the injected lesion is stable or responding, and non-injected lesions have not grown, patients may receive up to 2 additional courses of treatment. Patients receive one of the following antibiotic regimens upon evidence of progressive disease, DLT, or discontinuation from the study: First line: Ciprofloxacin IV or orally every 12 hours on day 1 then orally twice a day for 18 days Second line: Ceftriaxone IV on day 1 then cefixime orally for 16 days Third line: Co-trimoxazole orally twice a day for 21 days Patients are followed for an additional 4 weeks after initiation of antibiotic therapy.~PROJECTED ACCRUAL: A total of 12-40 patients will be accrued for this study. | RATIONALE: Biological therapies such as VNP20009 use different ways to stimulate the immune system and stop cancer cells from growing.~PURPOSE: Phase I trial to study the effectiveness of VNP20009 in treating patients who have advanced or metastatic solid tumors that have not responded to previous therapy. |
OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicities of gemcitabine in combination with oxaliplatin in patients with advanced malignancies. II. Determine the pharmacokinetics of oxaliplatin and gemcitabine in these patients.~OUTLINE: This is a multicenter, dose escalation study of gemcitabine. Patients receive oxaliplatin IV over 2 hours on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine in combination with a fixed dose of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicity.~PROJECTED ACCRUAL: A total of 24-36 patients will be accrued for this study within 2 years. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of oxaliplatin and gemcitabine in treating patients who have advanced cancer. |
OBJECTIVES: I. Determine if captopril can block or prevent lung injury in patients undergoing autologous bone marrow or stem cell transplantation following cyclophosphamide and total body radiotherapy or high dose chemotherapy. II. Determine a series of surrogate lung injury prediction markers for monitoring patients undergoing therapy.~OUTLINE: This is a randomized study. Patients are stratified according to preparative regimen (high dose chemotherapy versus cyclophosphamide and total body radiotherapy). Patients are randomized into one of two treatment arms. All patients undergo a conditioning regimen consisting of cyclophosphamide daily on days -6 and -5 and total body radiotherapy on day -4 through -1, or high dose chemotherapy per transplantation protocol. Arm I: Patients receive oral captopril 2 to 3 times daily beginning on the first day of the conditioning regimen and continuing until day 100 post autologous bone marrow or stem cell transplantation. Arm II: Patients receive no captopril while undergoing conditioning therapy. Patients are followed at 6 months.~PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study. | RATIONALE: Captopril may protect the lungs from the side effects of bone marrow or stem cell transplantation.~PURPOSE: Randomized phase III trial to determine the effectiveness of captopril to lessen the side effects in patients who are undergoing bone marrow or stem cell transplantation following chemotherapy and radiation therapy. |
PROTOCOL OUTLINE:~The parents of 1 family with known Mondini dysplasia are screened for the disorder using temporal bone computerized tomography without contrast. This information is used to determine the mode of inheritance. | OBJECTIVES:~I. Determine the mode of inheritance of nonsyndromal Mondini inner ear dysplasia, an inner ear malformation causing deafness, vestibular dysfunction, and recurrent meningitis. |
PROTOCOL OUTLINE: Pituitary size and anatomy and growth hormone response are evaluated.~All patients undergo MRI of the pituitary fossa on day 1. On day 2, homozygous patients receive a slow infusion of normal saline with blood sampling every 10 minutes. | OBJECTIVES: I. Assess pituitary size and anatomic configuration by magnetic resonance imaging (MRI) in 4 affected dwarfs in the province of Sindh, Pakistan.~II. Evaluate ultradian growth hormone (GH) secretory patterns in 4 affected dwarfs. |
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and Phase II dose of endostatin in patients with advanced refractory solid tumors. II. Determine the qualitative and quantitative nature of the toxicities encountered with endostatin in this patient population. III. Evaluate the basic pharmacokinetics and metabolism of endostatin by measurement of plasma levels by EIA and mass spectrometry in this patient population. IV. Investigate the relationship between pharmacokinetic parameters and toxicity in this patient population. V. Evaluate biologic evidence of angiogenesis inhibition in patients receiving endostatin.~OUTLINE: This is a dose escalation study. Patients receive endostatin IV over 1 hour daily for 28 days, followed by 1 week of rest. Patients receive subsequent courses of daily therapy in the absence of disease progression or unacceptable toxicity. Cohorts of 3 patients receive escalating doses of endostatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.~PROJECTED ACCRUAL: Approximately 30-40 patients will be accrued for this study. | RATIONALE: Endostatin may stop the growth of solid tumors by stopping blood flow to the tumor.~PURPOSE: Phase I trial to study the effectiveness of endostatin in treating patients who have advanced refractory solid tumors. |
OBJECTIVES: I. Determine the maximum tolerated dose, dose limiting toxicity, recommended phase II dose, and safety of BMS-214662 in patients with advanced solid tumors. II. Determine the pharmacokinetics of BMS-214662 in these patients. III. Assess the absolute oral bioavailability of BMS-214662 using a capsule and single intravenous dose in these patients. IV. Determine any preliminary evidence of antitumor activity of BMS-214662 in these patients.~OUTLINE: This is a dose escalation study. Patients receive BMS-214662 IV over 1 hour on day -7, followed by oral BMS-214662 daily on days 0-14 for course 1 only. Beginning with course 2, patients receive oral BMS-214662 twice daily for 14 days. Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which fewer than 2 of 6 patients experience dose limiting toxicity. Patients are followed every 4 weeks until toxicities resolve.~PROJECTED ACCRUAL: A total of 30-40 patients will be accrued for this study within 12-18 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of BMS-214662 in treating patients who have advanced solid tumors. |
OBJECTIVES: I. Determine the safety, tolerance, and maximum tolerated dose of TG4010 in patients with MUC1 positive advanced cancer. II. Determine the biological and immunological effects of this regimen in this patient population.~OUTLINE: This is a dose escalation study. Patients receive TG4010 IM weekly for 4 weeks, every other week for 8 weeks, and then every 4 weeks. Treatment continues every 4 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of TG4010 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience treatment related grade 3 toxicity. If any patient experiences grade 4 toxicity, the prior dose level is considered the MTD.~PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 4 months. | RATIONALE: Vaccines may make the body build an immune response to kill tumor cells.~PURPOSE: Phase I trial to study the effectiveness of vaccine therapy in treating patients who have advanced cancer. |
OBJECTIVES: I. Determine the maximum tolerated dose of irinotecan when combined with docetaxel in patients with advanced solid malignancies. II. Determine the dose limiting toxicity of this regimen in these patients. III. Assess any antitumor activity of this regimen in these patients.~OUTLINE: This is a dose escalation, multicenter study of irinotecan. Patients receive docetaxel IV over 1 hour followed immediately by irinotecan IV over 30 minutes on days 1, 8, 15, and 22. Treatment continues every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, then every 6 months thereafter.~PROJECTED ACCRUAL: Approximately 15-25 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I/II trial to study the effectiveness of docetaxel and irinotecan in treating patients who have advanced solid tumors. |
OBJECTIVES: I. Determine the maximum tolerated dose, dose limiting toxicities, safety, and a recommended phase II dose of BMS-247550 administered as a 1 hour infusion every 3 weeks in patients with advanced solid tumors. II. Evaluate the plasma pharmacokinetics of this drug in this patient population. III. Determine any preliminary evidence of antitumor activity of this drug in these patients.~OUTLINE: This is a dose escalation study. Patients receive BMS-247550 IV over 1 hour every 3 weeks. Treatment continues for a minimum of 2 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of BMS-247550 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities. Patients are followed every 3 months until death.~PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study within 8-12 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of BMS-247550 in treating patients who have advanced solid tumors that have not responded to previous therapy. |
OBJECTIVES: I. Determine the feasibility of administering multiple courses of carboplatin and topotecan without excessive dose modification or course delay in patients with previously untreated ovarian epithelial or primary peritoneal carcinoma. II. Describe the response rate and progression-free interval in these patients with this treatment regimen. III. Determine pharmacokinetic and pharmacodynamic parameters related to the sequence of carboplatin and topotecan administration in these patients.~OUTLINE: Patients are assigned to one of three treatment regimens. Regimen I: Patients receive carboplatin IV over 30 minutes on day 1 followed by topotecan IV over 30 minutes on days 1-3. Treatment continues every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment continues every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Regimen II: Patients receive topotecan IV over 30 minutes on days 1-3 followed by carboplatin IV over 30 minutes on day 3. Treatment continues every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment continues every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Regimen III: Patients receive topotecan IV over 30 minutes on days 1-5 followed by carboplatin IV over 30 minutes on day 5. Treatment continues every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment continues every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 1 month and then every 3 months for 1 year.~PROJECTED ACCRUAL: A total of 15-80 patients will be accrued for this study within 2 years. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have stage III or stage IV ovarian epithelial or primary peritoneal cancer. |
OBJECTIVES: I. Determine the antitumor activity of topotecan in patients with recurrent platinum sensitive ovarian epithelial or primary peritoneal cancer. II. Determine the nature and degree of toxicity of this treatment regimen in these patients.~OUTLINE: Patients receive topotecan IV over 30 minutes on days 1-3. Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.~PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase II trial to study the effectiveness of topotecan in treating patients who have recurrent ovarian epithelial or primary peritoneal cancer. |
DESIGN NARRATIVE:~The study was a subproject within a Specialized Centers of Research (SCOR) in Transfusion Medicine. The experimental design was based on the study and analysis of several unique sets of data. One set consisted of abstracted patient data including ICD-9-CM diagnosis and procedure, DRG and red cell units transfused, from a constant set 100 of United States hospitals for the years 1980,82,84,86, to which a new set of data was added for the year 1989. A similar set of data were gathered from eight cooperating teaching hospitals over the first four years of the grant term; this set included data for transfusions of all blood components, autologous units and factor preparations. A third data base contained the data for four United States surveys conducted in 1982,84,86,87; and was expanded to include 1990 and 92. Using these data, four main tasks were addressed. A Pan-DRG red cell transfusion study was conducted to ascertain red cell use across all DRGs and ICD-9-CM codes. Extensive efforts were devoted to developing new methods to characterize transfusion practice. A series of studies were devoted to characterizing transfusions of all blood components in a selected number of ICD-9-CM classes. The purpose of the fourth task was to develop simpler and more rapid alternative methods for producing national estimates of transfusion activity; as part of this task,new surveys were conducted for 1990 and 92.~Among the questions studied were: Was it possible to identify distinctive attributes of the patients who, though operated, did not require a transfusion or who required a large volume of blood? Were transfusions of non-red cell components related to use of red cells? Could transfusion frequency diagnosis for all blood products be used as a measure of transfusion practice? Did longitudinal comparisons of transfusions over the 9-year interval, 1980-1989, reveal significant trends? Was it possible to discriminate quantitatively between transfusion practices in different hospitals or set of hospitals, or at different times? What was the effect of autologous blood programs in transfusion practice? What was the contribution of comorbid conditions on red cell and component transfusion patterns.?~The dollars for the subproject were approximately 25 percent of total dollars spent each year for the Center.~The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System (PRS) record. | To develop and apply quantitative methods by which to measure and characterize blood transfusion practice in specific diagnoses and procedures; to open scientific communication about transfusion practice within and across institutions; and to develop simpler methods for estimating annual national blood collections and transfusions. |
BACKGROUND:~Accumulating data indicate that 70 to 80 percent of adults infected with the hepatitis C virus (HCV) develop persistent infection that may be associated with chronic hepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Despite these potential mortal outcomes, the progression is indolent, and serious chronic sequelae may not occur for 10 to 50 years, by which time many transfused adults have died of unrelated causes. Infants and children, on the other hand, are far more likely to survive their transfusion episode, to have a long life span after HCV acquisition and, by inference, to experience the decades-long evolution to HCV-related cirrhosis and hepatocellular carcinoma.~DESIGN NARRATIVE:~The years 1982-1992 have been selected because TAH incidence in adults was still high at that time and because all subjects would be under age 15 at enrollment and unlikely to have been exposed to sexual contact or IV drug use. Maternal testing is performed to exclude perinatal transmission. Sixty-five hundred children who meet the eligibility criteria of the study have been transfused at Children's National Medical Center (CNMC) during this period, and archival serum specimens are available for 22 percent. The total eligible cohort is contacted and asked to provide a blood sample that is tested for antibodies to HCV and to the newly discovered hepatitis G virus (HGV). Subjects found antibody positive on initial screen are enrolled in long-term followup that includes serial determinations for alanine aminotransferase (ALT), other liver-related assays, viral serology with confirmatory testing, PCR for HCV and HGV RNA, HCV genotyping and, in those with evidence of chronic hepatitis, liver biopsy. Biopsy may also be performed on a subset with chronic viremia, but normal ALT, pending approval of an advisory panel of liver experts. A serum repository will be established for evaluation of new diagnostic methods for HCV, HGV, and other etiologic agents of posttransfusion hepatitis.~This study will determine the minimal rate of transfusion-induced HCV and HGV infection and will allow for an annualized incidence estimate and a determination of the national burden of transfusion-induced hepatitis virus infection in children, a value that is currently unknown. In addition, by use of archival samples and the interval from transfusion to testing, the study will determine the duration of infection and rate of viral persistence. Finally, prospective followup with liver biopsy will establish the extent of disease in those chronically infected. If persistent infection and chronic liver disease are as common in children as in adults, this would have major implications for anti-viral therapy programs and might shift treatment emphasis to pediatric populations where response rates might be higher and where long-term benefit would be greater. | To identify a large cohort of children transfused in the decade prior to second-generation anti-hepatitis C virus (HCV) donor screening (1982-1992). This will not only identify cases for the study of persistent infection and chronic hepatitis in children, but will allow for the determination of the annualized risk of transfusion-associated hepatitis (TAH) infection in children, data that are not currently available. |
PRIMARY OBJECTIVES:~I. To determine the toxicity profile and MTD of low-dose SC IL-2 administered in conjunction with BIW regimen of IV rhIL-12.~II. To determine the antitumor effects of combination therapy with IV rhIL-12 and SC IL-2.~III. To determine the impact low-dose SC IL-2 has on the magnitude and duration of in vivo immune activation induced by a BIW schedule of IV rhIL-12.~OUTLINE: This is a dose-escalation study.~Patients receive interleukin-12 (IL-12) IV on days 1 and 4 for 6 weeks. Beginning on day 4 of the third week, patients receive interleukin-2 (IL-2) subcutaneously 1 hour before and 20 hours after each dose of IL-12. On subsequent courses, IL-2 and IL-12 are administered on days 1 and 4 of each week. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease response may continue treatment until complete response or disease progression.~Cohorts of 3-6 patients receive escalating doses of IL-12 and IL-2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.~Patients are followed at 3 weeks. | Phase I trial to study the effectiveness of interleukin-12 plus interleukin-2 in treating patients who have advanced solid tumors. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining the two drugs may kill more cancer cells |
OBJECTIVES: I. Determine the maximum tolerated dose and recommended phase II dose, dose limiting toxicities, and safety of BMS-188787 in patients with nonhematologic malignancies. II. Determine the plasma pharmacokinetics of BMS-188797 in these patients. III. Describe any antitumor activity of this treatment in these patients.~OUTLINE: This is a dose escalation study. Patients receive BMS-188797 IV over 1 hour. Treatment continues every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of BMS-188797 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Patients are followed every 4 weeks until toxicities resolve, and then at the investigator's discretion.~PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study over 12-18 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of BMS-188797 in treating patients who have advanced solid tumors that have not responded to previous treatment. |
OBJECTIVES: I. Determine the maximum target-inhibiting dose of SU5416 in patients with advanced solid tumors. II. Determine the relationship between dose or plasma levels and the clinical safety profile and antitumor effects of this treatment regimen in terms of objective response, stabilization of disease, or progression-free survival in this patient population. III. Evaluate the relationship between dose or plasma levels of SU5416 concentrations and the ability of this treatment regimen to reduce microvessel density and induce apoptosis of endothelial and tumor cells in this patient population. IV. Determine prognostic and surrogate serologic markers in these patients treated with this regimen. V. Determine if pre and posttreatment plasma and serum levels of angiogenic growth factors, basic fibroblast growth factor, and vascular endothelial cell growth factor are prognostic in predicting patient response to this regimen. VI. Determine if elevated plasma levels of endothelial cell specific proteins reflective of SU5416-induced endothelial damage and/or apoptosis are useful surrogate markers in assessing response to this treatment regimen in these patients.~OUTLINE: This is a dose-deescalation study. Patients receive SU5416 IV over 1 hour twice weekly for 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 6-12 patients receive deescalating doses of SU5416 until the maximum target-inhibiting dose (MTID) is determined. The MTID is defined as the dose at which patients experience no greater than grade 1 toxicity. Patients are followed every 3 months.~PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued for this study. | RATIONALE: SU5416 may stop the growth of cancer by stopping blood flow to the tumor.~PURPOSE: Phase I trial to study the effectiveness of SU5416 in treating patients who have advanced solid tumors. |
BACKGROUND:~The study continued research previously funded as part of a National Research and Demonstration Center (NRDC) in Transfusion Medicine.~DESIGN NARRATIVE:~There were six components to the study. The first identified significant factors influencing regular blood donations by individuals with different donation histories - first-time, second-time, committed (frequent), and lapsed donors. The second component developed and assessed the validity of behavioral models to increase donor retention and to predict whether first and second time donors would contribute again. The third developed donor-retention interventions, especially for the first and second time donors. The fourth component identified homogeneous subgroups among first, second and committed donors who might be receptive to different types of intervention strategies to increase the frequency of their donations. The fifth component evaluated the success of cost-effectiveness of the new interventions compared to existing blood center maintenance strategies. The sixth identified whether or not donors had a limit or ceiling on how often they donated per year.~The investigators drew on two related social psychological theories to combine cognitive and behavioral approaches to blood donor retention and to use the findings to construct a multiattribute model of donor decision-making. A behavioral decision model was used to predict donor behavior prospectively and to target and direct the design of interventions to increase donor retention and the frequency of donations.~Approximately 33 percent of the total project supported the subproject on retaining donors. | To retain individuals as blood donors once they have entered the voluntary blood donation system and to increase the frequency of their donations. |
BACKGROUND:~In 1986, the Department of the Navy initiated the National Bone Marrow Donor Registry. Because the support of a National Bone Marrow Donor Registry was not very closely related to the Navy's primary missions, in 1989 the management of the contract for the program was transferred by the Congress from the Navy to the NHLBI.~By 1989, bone marrow transplantation had become an effective and accepted treatment for an increasing number of diseases of the bone marrow and the immune system. Until only a few years prior to 1989, most marrow donors were siblings, carefully matched for HLA (tissue) antigens. Since only a small proportion of candidates for a bone marrow transplant have matched brothers or sisters, additional family members were tried as donors. These included parents, children, slightly mismatched siblings, and other relatives. Even with the broadening of the bone marrow donor source, no more than 30-40 percent of patients with diseases amenable to marrow transplant therapy had available donors. Improved results with these selectively mismatched relatives and a distinct need to provide appropriate treatment for more patients led to trials with unrelated, HLA-matched community volunteers as bone marrow donors. By 1989, research had progressed to the point where transplants from such unrelated donors were nearly as successful as those from matched siblings, when stratified by disease status and risk parameters. In 1989, 20 to 25 percent of patients for whom a formal donor search was initiated received a transplant. This was expected to increase substantially.~DESIGN NARRATIVE:~The program was established by the Department of the Navy in 1986 and transferred to the NHLBI in 1989. The purpose was to develop and maintain a registry of individuals willing to donate bone marrow for patients in need of transplants, to facilitate marrow transplants by serving as a coordinating and communications center for a network of donor, collection and transplant centers in the United States and internationally, and to facilitate research into the efficacy of unrelated donor marrow transplants. In 1992, the program was enlarged to support a limited number of demonstration projects to develop, implement, and evaluate innovative models for minority marrow donor recruitment. In 1995, the NMDP was transferred to the Health Resources and Services Administration (HRSA), although NHLBI provided funds in this year. | To serve as a focal point for bone-marrow research. |
OBJECTIVES:~Determine the maximum tolerated dose (MTD) of perifosine on a loading dose/maintenance dose schedule in patients with advanced solid tumors.~Determine the qualitative and quantitative toxic effects of this drug in these patients.~Determine the pharmacokinetics of this drug in these patients.~Investigate the relationship between pharmacokinetic parameters and toxicity of this drug in these patients.~Determine the recommended starting dose for phase II trials on this drug schedule in these patients.~Evaluate the pharmacodynamic parameters on peripheral blood lymphocytes both before and during drug administration in these patients.~Determine any changes in the MTD with prolonged administration (3 months, 6 months) of this drug in these patients.~OUTLINE: This is a dose-escalation study.~Patients receive a loading dose of oral perifosine 4 times a day for 4-8 doses followed by a daily maintenance dose. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.~Cohorts of 3-6 patients receive escalating loading doses and maintenance doses of perifosine until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxic effects.~PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued for this study. | RATIONALE: Perifosine may stop the growth of tumor cells by stopping blood flow to the tumor.~PURPOSE: Phase I trial to study the effectiveness of perifosine in treating patients who have advanced solid tumors. |
OBJECTIVES:~Determine the maximum tolerated dose of the combination of fenretinide, paclitaxel, and cisplatin in patients with advanced solid tumors.~Determine the effect of fenretinide on the pharmacokinetics of paclitaxel and cisplatin.~Assess the relationship between dose or plasma levels of fenretinide and the safety and antitumor effects, in terms of overall response, response rate, and progression-free survival rate, in these patients.~OUTLINE: This is a dose-escalation study of paclitaxel and cisplatin.~Patients receive oral fenretinide twice daily for 7 days. Patients receive paclitaxel IV over 3 hours and cisplatin IV over 30 minutes on day 7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of paclitaxel and cisplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive paclitaxel and cisplatin at the recommended phase II dose.~PROJECTED ACCRUAL: Approximately 15-24 patients will be accrued for this study within 12-24 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: This phase I trial is studying the side effects and best dose of combination chemotherapy in treating patients with advanced solid tumors. |
OBJECTIVES:~I. Determine the maximum tolerated dose of R115777 when administered with trastuzumab (Herceptin) in patients with advanced or metastatic adenocarcinoma.~II. Assess the toxicities and pharmacokinetics of this treatment regimen in this patient population.~III. Determine the antitumor activity of this treatment regimen in these patients.~IV. Determine the relative biologic endpoints of this regimen and correlate them with toxicity and pharmacokinetic parameters in these patients.~OUTLINE: This is a dose escalation, multicenter study of R115777.~Patients receive trastuzumab (Herceptin) IV over 90 minutes on days 1, 8, 15, and 22 plus oral R115777 twice daily for 3 weeks. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R115777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicities.~Patients are followed every 30 days until toxicity resolves. | Phase I trial to study the effectiveness of trastuzumab plus R115777 in treating patients who have advanced or metastatic cancer. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with R115777 may kill more tumor cells. |
OBJECTIVES:~Determine the dose-limiting toxic effects of R115777 and topotecan in patients with advanced solid tumors.~Determine the maximum tolerated dose of this regimen in these patients.~Determine pharmacokinetic profiles of topotecan alone and in combination with R115777 in these patients.~Measure the inhibition of ras-farnesylation and topo-1 inhibition in peripheral blood mononuclear cells in these patients when treated with this regimen.~Determine activity of this treatment in these patients.~OUTLINE: This is a dose-escalation, multicenter study.~Patients receive oral R115777 twice daily on days 2-21 (in the first course only R115777 begins on day 3) and topotecan IV continuously on days 1-21. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of R115777 and topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 6 patients experience dose-limiting toxicity.~PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of R115777 plus topotecan in treating patients who have advanced solid tumors. |
OBJECTIVES: I. Determine the maximum tolerated dose of BMS-214662 in combination with paclitaxel in patients with advanced solid tumors. II. Determine the safety and tolerability of this regimen in these patients. III. Determine the pharmacokinetics of this treatment regimen in this patient population. IV. Determine the pharmacodynamic effects of this treatment regimen in serial tumor biopsies in these patients. V. Determine the cytotoxicity of this treatment regimen in these patients.~OUTLINE: This is a dose-escalation study of BMS-214662. Patients receive paclitaxel IV over 3 hours on day 1 and BMS-214662 IV over 1 hour on day 3 of course 1. For all subsequent courses, patients receive paclitaxel IV over 3 hours followed 30 minutes later by BMS-214662 IV over 1 hour on day 1. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or objectively responding disease receive additional therapy at the investigator's discretion. Cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 4 weeks.~PROJECTED ACCRUAL: A maximum of 18-21 patients will be accrued for this study within 12-15 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of paclitaxel and BMS-214662 in treating patients who have advanced solid tumors. |
OBJECTIVES: I. Compare the effect of low dose radioactive seed localized breast biopsy versus needle localized breast biopsy on operative time and tissue loss in patients with nonpalpable breast lesions. II. Compare the cost effectiveness of these diagnostic methods in these patients. III. Demonstrate that radioactive seed localization allows for elimination of specimen x-ray in these patients. IV. Demonstrate that radioactive seeds may be placed safely for 1-7 days prior to surgical removal in these patients.~OUTLINE: This is a randomized study. Patients are randomized to one of two diagnostic arms. Arm I: Patients undergo radiographic placement of a radioactive seed (either iodine I 125 or palladium Pd 103) into the suspicious lesion. Patients then undergo surgery to remove the lesion along with the seed and a small margin of surrounding breast tissue followed 3 months later by a postoperative mammogram. Arm II: Patients undergo a needle localized breast biopsy with a specimen x-ray. | RATIONALE: Biopsy is the removal of cells or tissue for examination under a microscope. It is not yet known which type of breast biopsy is more effective for diagnosing breast lesions.~PURPOSE: Randomized diagnostic trial to compare the effectiveness of two different types of biopsy in patients who have breast lesions that cannot be felt upon examination. |
OBJECTIVES: I. Determine the maximum tolerated dose, dose limiting toxicity, and safety of nitrocamptothecin when administered with etoposide in patients with advanced solid tumors. II. Determine the changes in expression and activity of topoisomerase I and II which occur during administration of this treatment regimen in these patients. III. Determine the plasma pharmacokinetics of this treatment regimen in these patients. IV. Compare the hematologic and nonhematologic toxicities with this treatment regimen in patients 70 years of age and older versus patients younger than 70 years of age.~OUTLINE: This is a dose escalation study of nitrocamptothecin. Patients receive oral nitrocamptothecin on days 1-3 and oral etoposide on days 4-5 each week. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of nitrocamptothecin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Patients are followed every 4 weeks until toxicities resolve.~PROJECTED ACCRUAL: Approximately 40-60 patients will be accrued for this study over 18 to 24 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of nitrocamptothecin plus etoposide in treating patients who have advanced solid tumors. |
OBJECTIVES:~Determine the recommended phase II dose based on the maximum tolerated dose of BMS-188797 when administered with carboplatin in patients with advanced nonhematologic malignancies.~Assess the dose limiting toxicities and safety of this treatment regimen in these patients.~Determine the plasma pharmacokinetics of this treatment regimen in these patients.~Determine any antitumor activity of this treatment regimen in these patients.~OUTLINE: This is a dose escalation study of BMS-188797.~Patients receive BMS-188797 IV over 1 hour followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of BMS-188797 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose limiting toxicities.~Patients are followed for 4 weeks, and then every 3 months thereafter.~PROJECTED ACCRUAL: Approximately 35 patients will be accrued for this study over 12 months. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of BMS-188797 and carboplatin in treating patients who have advanced nonhematologic cancer. |
OBJECTIVES: I. Determine the safety, tolerability, and toxicity of 3-AP in patients with advanced malignancies. II. Determine the maximum tolerated dose and recommended phase II dose of this treatment in these patients. III. Determine the pharmacokinetic parameters of this treatment in these patients. IV. Determine the tumor response in these patients treated with this regimen.~OUTLINE: This is a dose escalation, multicenter study. Patients receive 3-AP IV continuously over 96 hours. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with complete response receive treatment for 1 course past the course in which the complete response was documented; patients with partial response may receive treatment for up to 1 year; and patients with stable disease may receive treatment for up to 6 months. During the accelerated phase of the study, cohorts of 1 patient each receive escalating doses of 3-AP until one patient experiences dose limiting toxicity (DLT) or 2 different patients experience grade 2 toxicity during any course. When the accelerated phase ends, cohorts of 3-6 patients receive escalating doses of 3-AP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT.~PROJECTED ACCRUAL: Approximately 21 patients will be accrued for this study. | RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of 3-AP in treating patients who have advanced cancer. |
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