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OBJECTIVES:~Determine the maximum tolerated dose or minimum effective dose and associated toxic effects of VNP20009 in patients with advanced solid tumors.~Determine whether VNP20009 can be detected in tumors after treatment in these patients.~Determine the pharmacokinetics of this treatment regimen in these patients.~Determine the antitumor effects of this treatment regimen in these patients.~OUTLINE: This is a dose-escalation study.~Patients receive VNP20009 IV over 4 hours on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response (CR) may receive additional courses every 35 days for up to 12 total doses or 2 courses past a CR.~Cohorts of 3-6 patients receive escalating doses of VNP20009 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. An additional 6-9 patients are treated at the MTD.~PROJECTED ACCRUAL: A total of 14-45 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 solid tumors.

OBJECTIVES:~Determine the maximum tolerated dose of SU5416 when combined with paclitaxel in patients with advanced malignancies.~Determine the toxicities and pharmacokinetics of this regimen in these patients.~Determine the effects of this regimen on a variety of histological and molecular biomarkers of angiogenesis, including in vitro activity assays of endothelial cell proliferation, migration, and invasion.~OUTLINE: This is a dose escalation study of SU5416.~Patients receive SU5416 IV over 1 hour twice weekly during the first week. During subsequent courses, SU5416 is administered on days 1, 4, 8, 11, 15, 18, 22, and 25. Paclitaxel begins on the second week of therapy and is administered IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of SU5416 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 24 patients will be accrued for this study within 12-18 months.

RATIONALE: Drugs such as SU5416 may stop the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining SU5416 with chemotherapy may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combining SU5416 and paclitaxel in treating patients who have advanced cancer.

OBJECTIVES:~Determine the antitumor activity of nitrocamptothecin in patients with recurrent or metastatic ovarian epithelial or primary peritoneal cancer.~Determine the nature and degree of toxicity of this regimen in these patients.~OUTLINE: Patients receive oral nitrocamptothecin on days 1-5. Treatment continues every 7 days in the absence of disease progression or unacceptable toxicity.~Patients are followed at 2 weeks, then every 3 months for 2 years, and then every 6 months for 3 years.~PROJECTED ACCRUAL: Approximately 19-51 patients will be accrued for this study within 22 months.

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 nitrocamptothecin in treating patients who have recurrent or metastatic ovarian epithelial or primary peritoneal cancer.

OBJECTIVES:~Determine the pharmacokinetic profile of gemcitabine, doxorubicin HCl liposome, and vinorelbine in patients with advanced solid tumors.~Determine the maximum tolerated dose of this regimen in these patients.~Determine the toxicity profile of this regimen in these patients.~OUTLINE: This is a dose escalation study.~Patients receive doxorubicin HCl liposome IV over 1-2.5 hours on day 1, gemcitabine IV over 30 minutes on days 1 and 8, and vinorelbine IV over 6-10 minutes on days 1 and 15. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, gemcitabine, and vinorelbine 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 every 3 months for up to 1 year.~PROJECTED ACCRUAL: Approximately 9-24 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 combination chemotherapy in treating patients who have advanced solid tumors.

OBJECTIVES:~Compare time to progression in patients with advanced ovarian epithelial carcinoma who failed prior first-line platinum-based therapy when treated with carboplatin with or without gemcitabine.~Compare response rate, duration of response, and survival time of patients treated with these regimens.~Compare the toxicity of these treatment regimens in these patients.~Compare quality of life of patients treated with these regimens.~OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to progression-free time (6-12 months vs more than 12 months), type of prior first-line therapy, and bidimensionally measurable disease (yes vs no). Patients are randomized to one of two treatment arms.~Arm I: Patients receive carboplatin IV over 30-60 minutes on day 1 and gemcitabine IV over 30-60 minutes on days 1 and 8.~Arm II: Patients receive carboplatin IV as in arm I. Treatment in both arms repeats every 3 weeks for up to 6-8 courses in the absence of disease progression or unacceptable toxicity.~Quality of life is assessed at baseline, before each subsequent chemotherapy course, and at 50 days after study.~Patients are followed at 50 days, every 2 months for 1 year, and then every 3 months for 1 year.~PROJECTED ACCRUAL: A total of 350 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. It is not yet known if carboplatin is more effective with or without gemcitabine for ovarian epithelial cancer.~PURPOSE: Randomized phase III trial to compare the effectiveness of carboplatin with or without gemcitabine in treating patients who have advanced ovarian epithelial cancer that has not responded to previous chemotherapy.

OBJECTIVES: I. Determine the toxicity and maximum tolerated dose of octreotide administered with doxorubicin in patients with advanced cancer. II. Determine the pharmacokinetics and pharmacodynamics of this treatment regimen in these patients.~OUTLINE: This is a dose escalation study of octreotide. Patients receive doxorubicin IV over 5 minutes on day 1 of course 1. For all subsequent courses, patients receive octreotide SC continuously on days 1-7 and doxorubicin IV over 5 minutes on day 5. Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease after 3 courses of therapy receive a maximum of 6 additional courses. Cohorts of 3-6 patients receive escalating doses of octreotide 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 21-30 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. Octreotide may help doxorubicin kill more cancer cells by making tumor cells more sensitive to the drug.~PURPOSE: Phase I trial to study the effectiveness of octreotide and doxorubicin in treating patients who have advanced cancer.

OBJECTIVES: I. Determine the maximum tolerated dose of gemcitabine and docetaxel when administered with carboplatin with or without filgrastim (G-CSF) in patients with advanced solid tumors. II. Determine a safe dose level and schedule for this regimen for phase II study in these patients. III. Determine the toxicity of this regimen in these patients.~OUTLINE: This is a dose-escalation study of docetaxel and gemcitabine. Patients receive gemcitabine IV over 30 minutes, docetaxel IV over 1 hour, and carboplatin IV over 30 minutes on day 1. Patients also receive gemcitabine IV over 30 minutes on day 8. Treatment repeats every 21 days for approximately 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine and docetaxel 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 (DLT). If the DLT is grade 4 neutropenia, filgrastim (G-CSF) is added to the regimen (administered subcutaneously on days 2-7 and 8-14 or until blood counts recover). A new MTD is then determined. Patients are followed every 3 months.~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. Colony-stimulating factors such as filgrastim 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 trial to study the effectiveness of gemcitabine combined with docetaxel and carboplatin with or without filgrastim in treating patients who have advanced solid tumors.

OBJECTIVES: I. Determine the maximum tolerated dose of etoposide when combined with fixed- dose fluorouracil-uracil plus leucovorin calcium in patients with advanced solid tumors. II. Determine possible side effects and toxicity of this regimen in these patients.~OUTLINE: This is a dose escalation study of etoposide. Patients receive oral etoposide daily on days 1-10 and oral fluorouracil-uracil plus oral leucovorin calcium twice a day on days 1-21. Treatment repeats every 28 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of etoposide 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. Patients are followed at 2 months and then periodically for survival.~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 chemotherapy drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have advanced solid tumors.

OBJECTIVES: I. Determine the maximum tolerated dose of weekly paclitaxel when combined with fluorouracil-uracil and leucovorin calcium in patients with solid tumors. II. Determine the side effects and toxicity of this regimen in these patients.~OUTLINE: This is a dose escalation study of paclitaxel. Patients receive paclitaxel IV on days 1, 8, and 15. Patients also receive oral fluorouracil-uracil and leucovorin calcium twice daily on days 2-6, 9-13, and 16-20. Treatment repeats every 4 weeks for up to 6 courses in the absence of progressive disease or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity. Patients are followed at 2 months and then for survival.~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 paclitaxel combined with fluorouracil-uracil and leucovorin in treating patients who have solid tumors.

PRIMARY OBJECTIVES:~I. To determine the maximum tolerated dose and toxicity profile of the novel CEA-based vaccine, rF-CEA(6D)-TRICOM (recombinant fowlpox-CEA(6D)-B7.1/ICAM-1/LFA-3), either alone or in combination with a second vaccine, rV-CEA(6D)-TRICOM (recombinant vaccinia-CEA(6D)-B7.1/ICAM-1/LFA-3) in patients with advanced CEA-bearing cancers.~II. To determine the maximum tolerated dose and toxicity profile of the novel CEA-based vaccine rV-CEA(6D)-TRICOM when given in combination with the maximum tolerated dose of rF-CEA(6D)-TRICOM, in patients with advanced CEA-bearing cancers.~III. To determine the safety and impact of colony stimulating factors (GM-CSF) on the immunologic response, when given in conjunction with the combination of rV-CEA(6D)-TRICOM (MTD) and rF-CEA(6D)-TRICOM (MTD) vaccines, in patients with advanced CEA-bearing cancers.~IV. To determine the change in CAP-1 directed T cells in patients treated with these vaccines using ELISPOT assay analysis.~V. To perform a pilot analysis of the impact of vaccine therapy on the quantity of circulating CEA-positive cells in the patients treated on this study in order to develop and eventually validate a practical, intermediate bio-marker for the immunologic response to the vaccines.~VI. To document any objective anti-tumor responses that occur.~OUTLINE: This is a dose-escalation study of fowlpox-CEA-TRICOM (fCEA-TRI) vaccine and vaccinia-CEA-TRICOM (vCEA-TRI) vaccine.~STAGE I: Patients receive fCEA-TRI vaccine subcutaneously (SC) once daily on days 1, 29, 57, and 85.~Cohorts of 3-10 patients receive escalating doses of the fCEA-TRI vaccine 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 (DLT).~STAGE II: Patients receive vCEA-TRI vaccine intradermally once on day 1 and fCEA-TRI vaccine SC at the MTD determined in stage I once daily on days 29, 57, and 85.~Cohorts of 3-10 patients receive escalating doses of the vCEA-TRI vaccine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT.~STAGE III: A single cohort of 6-10 patients receive both vaccines as in stage II, at the MTDs determined in stages I and II, and sargramostim (GM-CSF) SC once daily on days 1-4, 29-32, 57-60, and 85-88.~Patients in any stage of the study with responding disease may receive additional doses of the fCEA-TRI vaccine monthly for 2 months and then every 3 months thereafter. Patients who have objective evidence of response (including mixed response) and/or a fall in an elevated serum CEA level after the sixth vaccine and who subsequently develop disease progression while on the extended every 3-month treatment schedule and have no other potentially better treatment alternatives available may continue treatment as per the monthly vaccination schedule for 2 additional months. Patients with stable or responding disease after those two monthly vaccines may continue monthly vaccines at the discretion of the principal investigator.~Patients are followed at 4 weeks and then monthly for 3 months.

Phase I trial to compare the effectiveness of vaccine therapy with or without sargramostim in treating patients who have solid tumors. Vaccines may make the body build an immune response to kill tumor cells. Combining colony-stimulating factors such as sargramostim with vaccines may kill more tumor cells.

OBJECTIVES:~Determine the dose-limiting toxicity, maximum tolerated dose, and the recommended phase II dose of capecitabine and cisplatin in patients with locally advanced or metastatic cancer of the upper gastrointestinal tract (GI), head and neck, lung, breast, or carcinoma of unknown primary.~Determine the toxic effects of this regimen in these patients.~Evaluate possible antitumor effectiveness of this regimen in these patients.~Determine the toxic effects of cisplatin and capecitabine at the recommended phase II dose in patients with cancer of the upper GI tract.~Determine the overall survival, time to progression, and duration of response in patients treated with this regimen.~OUTLINE: This is a dose-escalation study of capecitabine.~Patients receive oral capecitabine twice daily for 5, 10, or 14 days. Patients also receive cisplatin IV on day 1 of each course. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). The recommended phase II dose is defined as the dose preceding the MTD, provided no more than 3 of 12 patients experience DLT at that dose. Twenty additional patients with cancer of the upper gastrointestinal tract receive treatment with cisplatin and capecitabine at the recommended phase II dose for at least 6 months in the absence of disease progression or unacceptable toxicity.~Patients are followed every 3 months for 6 months and then every 6 months thereafter.~PROJECTED ACCRUAL: A total of 20-50 patients will be accrued for this study within 1-3 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 chemotherapy drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of capecitabine combined with cisplatin in treating patients who have locally advanced or metastatic solid tumors .

OBJECTIVES:~I. Determine the dose-limiting toxicity and the maximum tolerated dose of benzoylphenylurea in patients with advanced malignancy.~II. Determine the pharmacokinetics of this drug in these patients.~OUTLINE: This is a dose-escalation study.~Patients receive oral benzoylphenylurea weekly for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of benzoylphenylurea 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: A total of 3-30 patients will be accrued for this study.

This phase I trial is studying the side effects and best dose of benzoylphenylurea in treating patients with advanced cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die

This Phase I study will assess the pharmacokinetics of two botanicals, Trifolium pratense (red clover) and Cimicifuga racemosa (black cohosh). Participants will receive a single dose of one botanical preparation. The observation period will be one week. Drug toxicity, absorption, distribution, metabolism and elimination data will be collected, and dosages to be utilized in a Phase II clinical trial will be determined. The Phase II trial will examine the efficacies of red clover and black cohosh for the reduction of menopausal symptoms in healthy menopausal women. The study will be randomized, double-blinded, and placebo-controlled. Study duration will be one year.

This Phase I study will assess the pharmacokinetics of two botanicals, Trifolium pratense (red clover) and Cimicifuga racemosa (black cohosh). Participants will receive a single dose of one botanical preparation. The observation period will be one week. Drug toxicity, absorption, distribution, metabolism and elimination data will be collected, and dosages to be utilized in a Phase II clinical trial will be determined.

Background:~Many patients with diabetes are under sub-optimal glycemic control. Central to the clinician's task in improving glycemic control is the management of hypoglycemic medication therapy, including the use of drugs such as insulin and sulfonylureas. Clinical trials have demonstrated that more intensive hypoglycemic medication therapy results in improved glycemic control. Yet quality measures for this critical process of care have not been developed and we know little about how physicians actually manage hypoglycemic medications.~Objectives:~We propose to develop a quality measure that describes the intensity of physicians' hypoglycemic medication therapy. We will then provide feedback to VA physicians regarding their practices and access to experts in diabetes care to determine whether this intervention leads to improvements in glycemic control.~Methods:~The study was divided into two phases. During the first phase we used existing data to model the decision to increase hypoglycemic medications. At each medical visit, we determined whether an increase in medication therapy occurred. We then used recursive partitioning to develop a model that identified patient characteristics at the visit, such as recent laboratory results and diagnoses, associated with the decision to increase therapy. This model assigns a predicted probability of an increase in therapy to each visit. We used these predictions to define an intensity of hypoglycemic medication therapy for each physician that compared the actual to predicted number of increases over all patient-visits. The second phase was a randomized trial in which clinicians at experimental sites receive feedback on performance and access to expert opinion while usual care is provided at control sites. Feedback on performance was provided twice over 6 months. The change in intensity of treatment scores and glycosylated hemoglobin levels pre- and post-intervention at these sites were compared to performance of primary care physicians at control sites not receiving the intervention.~Status:~Completed.

Many patients with diabetes are under sub-optimal glycemic control. Central to the clinician's task in improving glycemic control is the management of hypoglycemic medication therapy, including the use of drugs such as insulin and sulfonylureas. Clinical trials have demonstrated that more intensive hypoglycemic medication therapy results in improved glycemic control. Yet quality measures for this critical process of care have not been developed and we know little about how physicians actually manage hypoglycemic medications.

Background:~This study was designed to assess the effectiveness of a Health Education Program (HEP) for improving the well-being and reducing the health care use and cost of care of frail older outpatient veterans, and for improving the well-being of their spouse caregivers. HEP is a multi-component group program delivered in 8 weekly, 2-hour sessions, and 10 monthly 2-hour follow-up sessions, it includes emotion-focused and problem focused coping strategies, education and support.~Objectives:~The objectives of this study are to evaluate: 1) effects of HEP on the perceived health status, emotional well-being, and social support of frail veterans; 2) effects of HEP on the perceived health, emotional well-being, social support, burden levels, self-appraisal of change, pressing problems associated with caregiving, knowledge and use of community resources by caregiver; and 3) effects of HEP on the health care use and costs of care recipients.~Methods:~HEP was evaluated using a randomized control group design. The design has two levels of intervention, HEP vs. Usual Care (UC), 3 VA medical centers (VAMCs), and 4 times of measurement (at baseline, after the 8th HEP meeting, and at 1 and 2 years after baseline). Data reported here are for 8 week and 1-year psychosocial outcomes and 18 months for VA cost. Caregivers and veterans (n = 466) were randomized in 3 VAMCs, 114 to UC and 119 to HEP. The typical caregiver was 68 years old, married, white, female, with some college education and living with the veteran. The typical veteran care recipient was 74 years old, white, male with some college education, and suffered from one or more chronic health problems. Fifteen HEP groups were conducted. Caregivers and recipients were assessed on: 1) health and functional status; 2) emotional well-being; and 3) social support. In addition, caregivers were assessed for change in coping skills, change in burden level, pressing problems, and knowledge and use of community resources. Data was analyzed using random effects regression models.~Status:~Data on two-year outcomes for health and functional status, emotional well-being, and social support of caregivers and veterans, problems associated with caregiving and Medicare plus VA costs are being collected and analyzed for an amended final report.

This study was designed to assess the effectiveness of a Health Education Program (HEP) for improving the well-being and reducing the health care use and cost of care of frail older outpatient veterans, and for improving the well-being of their spouse caregivers. HEP is a multi-component group program delivered in 8 weekly, 2-hour sessions, and 10 monthly 2-hour follow-up sessions, it includes emotion-focused and problem focused coping strategies, education and support.

Background:~The decision regarding the use of post-menopausal estrogen hormone replacement therapy (HT) is complex because patients must balance the short and long-term risks and benefits. Information from new and important clinical trials must also be considered. The purpose of this research is to develop and evaluate the efficacy of a HT CD-ROM decision-aid in improving the decision making process for women considering the use of estrogen HT.~Objectives:~The objectives of the study are to: 1) develop a model of the decision-making process for postmenopausal women considering hormone (HT), based on Multi-Attribute Utility Theory (MAUT); 2) produce an interactive CD-ROM decision-aid for HT; 3) evaluate the effect of the interactive CD-ROM decision-aid on patient satisfaction with decision (SWD) and knowledge about menopause and HT; and 4) test the effect of the interactive CD-ROM decision-aid on women�s decisions regarding use of HT.~Methods:~Phase I (completed) used structured interviews and surveys in the development of a decision model for HT. In phase II, an interactive CD-ROM decision-aid was developed and a randomized controlled trial (RCT) of its effect on decision processes was conducted. Postmenopausal women, aged 45-74 were recruited from the primary care clinics of the four participating Veterans Affairs hospitals: Milwaukee, Madison, Chicago-Hines, and Chicago-Westside. The primary hypothesis was that women who use the CD-ROM decision-aid would demonstrate increased satisfaction with their decision regarding hormone replacement therapy use compared to women receiving the control intervention.~Status:~Enrollment and follow-up assessments have been completed. The study is in the analysis phase. The study was presented to the VA HSR&D Combined Monitoring Board on February 5, 2003 and the committee voted unanimously to recommend continuation of the trial. The study has had one publication and several scientific abstract presentations.

The decision regarding the use of post-menopausal estrogen hormone replacement therapy (HT) is complex because patients must balance the short and long-term risks and benefits. Information from new and important clinical trials must also be considered. The purpose of this research is to develop and evaluate the efficacy of a HT CD-ROM decision-aid in improving the decision making process for women considering the use of estrogen HT.

Background:~Smoking is a serious and common health risk among veterans. Given the press of national initiatives and local incentives to improve smoking cessation care in response to VA performance measures, this study tests a widely applicable approach to clinical practice guidelines implementation, namely evidence-based quality improvement, which is directly relevant to the translation of efficacious treatments into enhancements in VA health care policy and practice. Evidence-Based Quality Improvement (EBQI) focuses on improved provider adherence to smoking cessation guidelines and a decrease in patient smoking rates in a manner designed to produce short- and long-term health improvements and cost benefits at the organizational level.~Objectives:~Adherence to smoking cessation guidelines requires practice changes at the patient, provider, and system levels to achieve optimal quit rates. The objective of this study was to evaluate the effectiveness of evidence-based quality improvement (EBQI)�an expert-designed and locally implemented clinical reorganization of smoking cessation care�on changes in smoking cessation (SC) practice among primary care providers and health outcomes among veteran smokers.~Methods:~An evidence-based quality improvement intervention comprising provision of physician and patient educational materials, local priority setting with leadership and providers, and local adaptation of expert-designed protocols was implemented in experimental VA primary care practices (n=9). VA control sites (n=9), matched on size and academic affiliation, received smoking cessation guideline copies. We randomly sampled, consented, screened and surveyed primary care patients at all 18 sites (n=1,941 smokers) and used computer-assisted telephone interviewing to assess sociodemographics, health status, function, and smoking behavior, attitudes and treatment experience. Post-intervention 12-month follow-up interviews were completed using the same measures (n=1,080). We used multiple imputation using hotdeck techniques and applied both enrollment and attrition weights to the patient-level data. We used weighted logistic regression to evaluate intervention effects, controlling for patient-level predictors of quit attempts and quit status (e.g., level of addiction, readiness to change, age, health).~Status:~The project is completed. Analysis is ongoing for manuscripts.

Smoking is a serious and common health risk among veterans. Given the press of national initiatives and local incentives to improve smoking cessation care in response to VA performance measures, this study tests a widely applicable approach to clinical practice guidelines implementation, namely evidence-based quality improvement, which is directly relevant to the translation of efficacious treatments into enhancements in VA health care policy and practice. Evidence-Based Quality Improvement (EBQI) focuses on improved provider adherence to smoking cessation guidelines and a decrease in patient smoking rates in a manner designed to produce short- and long-term health improvements and cost benefits at the organizational level.

Background:~Among veterans, smoking is the single most important risk factor for preventable mortality and morbidity, and studies suggest a higher prevalence of smoking among veterans than the general population. The VHA has encouraged adoption of the AHCPR Guideline for Smoking Cessation, yet most hospitals have poorly developed smoking cessation programs.~Objectives:~The present study is designed to investigate the effectiveness of an organizational strategy to increase compliance with the AHCPR guideline. Short term goals of the study include increasing the rate of identification of smokers and increasing the delivery of brief smoking cessation interventions. Long term goals include reducing tobacco consumption among veterans.~Methods:~Twenty VAMC�s with active primary care clinics have been randomly assigned to either control (usual practice; UP) or intervention (organizational support; OS) groups. The intervention hospitals receive staff training and site consultation; all hospitals will receive the AHCPR guideline. Rate of identification of smokers in the medical record, smoking cessation rates, provision of smoking cessation services (e.g., NRT, counseling), and costs of NRT will be determined via telephone interviews with patients, chart review, and electronic records.~Status:~Baseline data collection is nearly complete, and the intervention period will be complete in September, 2000. We have completed telephone surveys with approximately 4500 veterans. Analysis of study data is ongoing, and manuscript preparation will begin within the next few months.

Among veterans, smoking is the single most important risk factor for preventable mortality and morbidity, and studies suggest a higher prevalence of smoking among veterans than the general population. The VHA has encouraged adoption of the AHCPR Guideline for Smoking Cessation, yet most hospitals have poorly developed smoking cessation programs.

Background:~Control of the blood sugar prevents complications and results in extra years of life in patients with diabetes. Practice Guidelines delineating specific ways physicians manage diabetes have been outlined. Missing are guidelines for health care providers to encourage patients to take responsibility for their diabetes. Traditional patient education models have been ineffective in managing diabetic persons because they have relied upon information given alone and are disease centered rather than patient centered. This study will explore the role of self-efficacy in helping veterans move toward healthy behaviors.~Objectives:~The long-term objectives are to: 1) increase recognition of veteran�s responsibility for health; 2) develop more effective skills in managing chronic conditions; and 3) explore the role of self-efficacy in facilitating improvements in health behaviors and health care utilization.~Methods:~This is a prospective, randomized controlled clinical trial of 2,068 cognitively intact, diabetic veterans. The outcome measures (health behaviors, self-efficacy, health status and health care utilization) will be measured using self-rated scales developed and tested by Lorig and colleagues from Stanford University. Glucose levels and BMI changes will be evaluated using information documented in the medical record.~Status:~Enrollment (a total of 326 patients) is closed. All necessary data have been received and are being analyzed.

Control of the blood sugar prevents complications and results in extra years of life in patients with diabetes. Practice Guidelines delineating specific ways physicians manage diabetes have been outlined. Missing are guidelines for health care providers to encourage patients to take responsibility for their diabetes. Traditional patient education models have been ineffective in managing diabetic persons because they have relied upon information given alone and are disease centered rather than patient centered. This study will explore the role of self-efficacy in helping veterans move toward healthy behaviors.

Background:~Health care organizations, including the VA, are investing substantial effort to improve quality of care. As part of this process, greater emphasis is being placed on measurement of outcomes, and in particular, functional outcomes and satisfaction as reported by patients.~Objectives:~ACQUIP was designed to determine whether quality and outcomes of health care improve when primary care providers have access to regular assessments of their patients' health and function along with routine clinical data and information about clinical guidelines.~Methods:~This study was a randomized trial conducted at the General Internal Medicine Clinics of seven VA facilities. Each participating GIMC is organized into discrete firms staffed by different groups of providers who care for different patients. One randomly selected firm received the intervention and one served as control. Patients who made at least one GIMC visit in the last year were eligible to participate. Patients were surveyed at baseline to determine active medical problems. Subsequent mailings included a general evaluation of health status (SF-36), a satisfaction questionnaire and, as appropriate, one of six condition-specific questionnaires: the Seattle Angina Questionnaire, the Seattle Obstructive Lung Disease Questionnaire, the Hopkins Symptom Checklist (depression), and questionnaires regarding diabetes, drinking, and hypertension. Clinical/utilization data were downloaded weekly from VISTA and supplemented with data from Austin. The intervention consisted of multi-faceted reports to patients' primary care providers (at the time of patient visits) showing trended physiologic and health status data and guideline-derived recommendations. Clinicians also received periodical reports displaying trends in the health status and satisfaction of their patients compared with their clinic as a whole. Reports were supplemented by training on QI and health status measures.~Status:~Data collection was completed on April 1, 2000. Analysis of trial results will be completed January, 2001.

Health care organizations, including the VA, are investing substantial effort to improve quality of care. As part of this process, greater emphasis is being placed on measurement of outcomes, and in particular, functional outcomes and satisfaction as reported by patients.

Background:~A variety of models of psychiatric hospital alternative care have been developed over the past several decades. San Diego�s Short-Term Acute Residential Treatment (START) model is one of the best established of these alternatives, comprising a network of 6 facilities with a total of 77 beds. Although veterans have been among those served at START programs for many years, no previous study of START or any other model has focused specifically on veterans.~Objectives:~The study tested the hypotheses that veterans treated in a START program would demonstrate greater improvement in symptoms and quality of life, as well as greater satisfaction with treatment and lower costs of care than veterans treated at the VA inpatient unit.~Methods:~This study includes elements of both efficacy and effectiveness studies. VA psychiatric unit treatment and START are compared in a randomized trial, with follow up of subjects at 2, 6, and 12 months as they experience real-world treatment-as-usual. Symptoms, functioning, quality of life, and satisfaction with services are assessed on multiple standardized measures, as well as by qualitative assessments.~Status:~Final report is under preparation.

A variety of models of psychiatric hospital alternative care have been developed over the past several decades. San Diego�s Short-Term Acute Residential Treatment (START) model is one of the best established of these alternatives, comprising a network of 6 facilities with a total of 77 beds. Although veterans have been among those served at START programs for many years, no previous study of START or any other model has focused specifically on veterans.

Background:~We have previously shown (IIR 95-045) that teledermatology, using store and forward technology, can result in reliable and accurate diagnostic outcomes when compared to clinic-based dermatology consultations. This investigation builds on that fundamental diagnostic information by assessing the health services implications of a teledermatology consult system.~Objectives:~To investigate health services outcomes related to teledermatology implementation. Outcomes of interest were time to diagnosis and treatment initiation, the proportion of patients that avoided the need for a clinic-based encounter, and an economic analysis.~Methods:~Patients referred from the primary care clinics to the dermatology consult service were randomized to either usual care or a teledermatology consultation. A usual care consultation consisted a conventional text-based electronic consult request. A teledermatology consultation included digital images and a standardized history, in addition to the electronic text-based consult. Consultant dermatologists, reviewing the consult requests for both modalities, decided when, and if, a referral required a clinic-based evaluation.~Status:~Final report has been prepared and is in the review process at this time.

We have previously shown (IIR 95-045) that teledermatology, using store and forward technology, can result in reliable and accurate diagnostic outcomes when compared to clinic-based dermatology consultations. This investigation builds on that fundamental diagnostic information by assessing the health services implications of a teledermatology consult system.

OBJECTIVES:~Determine the dose-limiting toxic effects and maximum tolerated dose of flavopiridol and docetaxel in patients with advanced solid tumors.~Determine the objective response rate and duration of response in patients treated with this regimen.~Determine the pharmacokinetics of these drugs in this patient population.~OUTLINE: This is a dose-escalation study.~Patients receive docetaxel IV over 60 minutes on day 1 and flavopiridol IV continuously over 24 hours on day 2. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of docetaxel and flavopiridol 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: A total of 18-24 patients will be accrued for this study within 9-11 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 combining flavopiridol and docetaxel in treating patients who have advanced solid tumors.

OBJECTIVES:~Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan in children with refractory or progressive solid tumors.~Determine the pharmacokinetics of this drug and its metabolites (SN-38, SN-38G, and APC) administered with and without concurrent anticonvulsants in this patient population.~Determine the benefit this drug offers this patient population.~OUTLINE: This is a dose-escalation, multicenter study. Patients are accrued into stratum 1 initially and into stratum 2 if stratum 1 closes due to dose-limiting toxicity of myelosuppression or diarrhea. Patients on anticonvulsants will be accrued into stratum 3 and must meet the eligibility criteria for the stratum that is open (stratum 1 or stratum 2). (Stratum 1 closed as of 2002-09-15).~Patients receive irinotecan IV over 90 minutes 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 irinotecan until the maximum tolerated dose (MTD) with and without anticonvulsants 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 every 6 months for 4 years and then annually thereafter.~PROJECTED ACCRUAL: Approximately 20-25 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.~PURPOSE: Phase I trial to study the effectiveness of irinotecan in treating children who have refractory or progressive solid tumors.

OBJECTIVES:~Determine the maximum tolerated dose and dose-limiting toxic effects of AG2037 in patients with advanced, metastatic, or recurrent solid tumor.~Determine the safety and tolerance of this drug in these patients.~Assess the pharmacokinetics of this drug in these patients.~Document any antitumor effects of this drug in these patients.~OUTLINE: This is a dose-escalation, multicenter study.~Patients receive AG2037 IV weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of AG2037 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 weekly for 4 weeks.~PROJECTED ACCRUAL: A total of 18-60 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 I trial to study the effectiveness of AG2037 in treating patients who have advanced, metastatic, or recurrent solid tumors.

If Islet Cell transplants are to become a reasonable treatment alternative for patients with type 1 diabetes, there must be knowledge about how the islet cells function after transplant {islet cells are responsible for making the insulin the body needs in order to control blood sugar). This knowledge would allow for improvements in the islet cell transplant procedure itself, as well as possible alterations of the immunosuppressive medications (drugs that prevent rejection) that are prescribed. There are two basic kinds of diabetes, type 1 (formally known as Insulin Dependent or Juvenile diabetes) and type 2 (formally known as Adult-Onset or Non-insulin dependent) diabetes. The patients in this study will be affected by type 1 diabetes. After the transplant, it is hoped they will no longer need insulin injections. It is possible patients may need to take pioglitazone and/or metformin, however, this will be prescribed in Project 1, if needed.~The medications used for this study include: C-peptide. This is a synthetic product (not from human or animal sources) that is man-made and identical to the C-peptide made by the body. C-peptide is made at the same time as insulin, one molecule of insulin equals one molecule C-peptide. By giving C-peptide that is synthetic, researchers can measure how the C-peptide breaks down in the body, which could then be related to how insulin breaks down in the body. Somatostatin will also be used during the same test as the C-peptide. While receiving Somatostatin, the production of insulin by the patient will be stopped. This medication will only be given for 4 hours and the blood sugar will be monitored during the entire procedure. Insulin & Glucose will also be given by IV during certain tests to regulate the blood sugar. Blood sugars will be maintained within a certain level and this will be achieved through the administration of insulin and/or glucose. The patient's blood sugar will be monitored at frequent intervals throughout the various procedures.

This grant is to study patients that have received a kidney transplant AND an Islet Cell transplant and to discover how the transplant is functioning. We will seek to have several patients who have had a kidney transplant but do NOT have either type of diabetes. These patients will serve as the control group since they will also be on immunosuppressive medications but are not affected by abnormal blood sugars. This will allow investigators to develop an understanding of how these immunosuppressive medications affect glucose metabolism (blood sugar levels) and insulin utilization (how the body uses insulin).

Previous studies have found that nicotine/mecamylamine treatment more than doubles the long-term abstinence rates relative to nicotine replacement alone. Recent evidence supports the hypothesis that nicotine/mecamylamine treatment prior to smoking cessation partially blocks the rewarding effects of cigarette smoking and hence promotes extinction of the smoking habit, facilitating subsequent abstinence. The behavioral approach employed is also an extinction strategy and involves having smokers switch to de-nicotinized tobacco cigarettes for two weeks prior to quitting smoking. It is hypothesized that the use of de-nicotinized cigarettes might provide more complete extinction than provided by the partial pharmacologic blockade using nicotine/mecamylamine alone. The pharmacologic treatment was expected to increase compliance with the de-nicotinized cigarette smoking regimen, because subjects' usual brands of cigarettes will be less appealing than in the absence of nicotine/mecamylamine treatment. Together the brand-switching and nicotine/mecamylamine therapies were expected to reduce cravings and other withdrawal symptoms as well as increase long-term abstinence from smoking.

This protocol evaluates the efficacy of combining pharmacologic treatments for smoking cessation, entailing the use of the nicotine skin patch with the nicotinic antagonist mecamylamine, with a specific behavioral therapy designed to inhibit the smoking urge.

Veterans will be of comparable body composition and age, and randomly assigned to either aerobic or resistive exercise. They will be instructed in a weight maintenance diet prior to beginning the exercise program, and maintain this diet throughout the study. Metabolic testing will be performed at baseline and after 6 months of exercise training. Testing will include measurement of body composition (anthropometry, dual-energy Xray absorptiometry, computed tomograph scan), maximal oxygen consumption, and muscle strength, glucose tolerance (oral glucose tolerance test), insulin sensitivity (euglycemic-hyperinsulinemic clamp), and muscle biopsies to examine skeletal muscle metabolic characteristics (fiber type distribution, capillary density, oxidative and glycolytic enzyme activities, and levels of key proteins important in insulin signaling and glucose transport). Data will be analyzed using analysis of variance to determine differences between the two exercise groups, and multiple regression analysis to determine the primary adaptations that are associated with the improvements in whole body insulin action.

This study will determine whether the metabolic and cellular mechanisms contributing to improved insulin action after aerobic or resistive exercise are different in older, obese, insulin resistant veterans. The hypothesis is that regular exercise, whether aerobic or resistive, will improve whole body insulin action, but the nature and magnitude of changes in skeletal muscle will differ between the two types of exercise.

The active intervention, MEMS Feedback, involves review of patients' medication-taking over the preceding weeks

This is a randomized controlled trial of adherence. The study involves monitoring and managing focused intervention in patients prescribed metformin.

OBJECTIVES: I. Determine the feasibility of expansion and the reinfusion of specific T-cell lines (peptide-specific activated lymphocytes), in combination with interleukin-2, in patients who were vaccinated with ras peptides. II. Assess immunologic status or antitumor response that may occur with this treatment in these patients.~OUTLINE: Autologous peptide-specific activated lymphocytes (PAL), previously harvested from the patient following vaccination on a different protocol, are expanded and reinfused intravenously; this is followed by a 4 hour observation period. Patients then receive interleukin-2 (IL-2) administered subcutaneously 5 days a week for 2 weeks; the first dose of IL-2 is administered at least 4 hours after PAL infusion. Patients are followed once a month for 2 months after treatment.~PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining white blood cells, which have been activated by a vaccine, with interleukin-2 may kill more cancer cells.~PURPOSE: Phase I trial to study the effectiveness of interleukin-2 plus activated white blood cells in treating patients with cancer that has not responded to chemotherapy or radiation therapy.

OBJECTIVES:~Determine the recommended phase II dose of irinotecan, leucovorin calcium, and fluorouracil in patients with advanced solid tumors.~Determine the toxic effects of this regimen in these patients.~Determine the pharmacokinetic and pharmacodynamic profiles of irinotecan and fluorouracil in patients treated with this regimen.~Determine the correlation of polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity and response in patients treated with this regimen.~Determine the correlation of polymorphisms in the uridine diphosphate glucuronosyltransferase 1A1 gene promoter with the extent of SN-38 glucuronidation and severity of diarrhea in patients treated with this regimen.~Assess any anti-tumor activity of this regimen in these patients.~OUTLINE: This is a dose-escalation study of irinotecan and fluorouracil.~Patients receive irinotecan IV continuously over 24 hours on days 1 and 15 and leucovorin calcium IV over 30 minutes followed by fluorouracil IV continuously over 48 hours on days 2 and 16. Treatment repeats every 28 days for at least 2 courses 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. Once the MTD of irinotecan has been determined, additional cohorts receive escalating doses of fluorouracil until the 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.~PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study within 20 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 combination chemotherapy in treating patients who have advanced solid tumors.

OBJECTIVES: I. Determine if families who participate in a video support program function better as a family in the areas of communication, togetherness, and overall increased ability to cope when a parent is newly diagnosed with cancer. II. Determine if participation in this program decreases stress-related illness in the well members of the family. III. Determine the safety of this program. IV. Determine patient/family and medical provider satisfaction with this program.~OUTLINE: This a randomized study. Adult parent participants and spouses undergo a baseline assessment over approximately 1 hour comprising completion of a self-assessment form followed by an interview. Families are then randomized to one of two arms. Arm I: Adult parent participants receive a video support program comprising 3 videotapes (parent tape, adolescent tape, and child tape) and a parent guidebook. The parents are encouraged to screen the videotapes and decide whether to have their child and/or adolescent view the program. Arm II: Adult parent participants receive no video support material. Families may view the video program after study completion. Adult parent participants in both arms complete follow-up assessments at 6 and 12 weeks. This clinical trial is being conducted at the locations listed below. If you are interested in this clinical trial but unable to visit these locations, please call #1-800-848-3895 ext. 226 and ask for more information about the We Can Cope study.~PROJECTED ACCRUAL: A total of 230 families will be accrued for this study.

RATIONALE: A videotape support program may help families improve communication and coping skills when a parent is diagnosed with cancer.~PURPOSE: Randomized trial to study the effectiveness of a video support program for families who have a parent who has been newly diagnosed with cancer.

OBJECTIVES:~Determine the maximum tolerated dose of continuous infusion gemcitabine in patients with metastatic malignancies.~Determine the toxicity profile of this drug in these patients.~OUTLINE: This is a dose-escalation study.~Patients on dose levels 1-5 receive gemcitabine IV continuously over 72 hours on week 1. Patients on dose levels 6 and 7 receive gemcitabine IV continuously over 72 hours on weeks 1-3. Courses repeat every 2 weeks (for patients on dose levels 1-5) and every 4 weeks (for patients on dose levels 6 and 7) in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 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 3 of 6 patients experience dose-limiting toxicity.~PROJECTED ACCRUAL: A total of 27 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 gemcitabine given as a continuous infusion in treating patients who have advanced metastatic cancer.

OBJECTIVES:~Determine the antitumor activity of tirapazamine and cisplatin in patients with persistent or recurrent platinum-sensitive ovarian epithelial or primary peritoneal carcinoma.~Determine the nature and degree of toxicity of this regimen in these patients.~OUTLINE: This is a multicenter study.~Patients receive tirapazamine IV over 2 hours followed 1 hour later by cisplatin IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.~Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.~PROJECTED ACCRUAL: A total of 20-65 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 II trial to study the effectiveness of combining tirapazamine with cisplatin in treating patients who have recurrent ovarian epithelial or primary peritoneal cancer.

OBJECTIVES:~Determine the dose-limiting toxicity and maximum tolerated dose of epirubicin and irinotecan in patients with advanced cancer.~Determine the objective antitumor responses in patients treated with this regimen.~Determine the pharmacokinetics of this regimen in these patients.~OUTLINE: This is a dose-escalation study.~Patients receive irinotecan IV over 1 hour followed by epirubicin IV over 5 minutes on days 1 and 8. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.~Sequential dose escalation of epirubicin is followed by sequential dose escalation of irinotecan. Cohorts of 3-6 patients receive escalating doses of epirubicin and irinotecan 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 toxicity.~PROJECTED ACCRUAL: A total of 3-30 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 epirubicin plus irinotecan in treating patients who have advanced cancer.

OBJECTIVES:~I. Determine the maximum tolerated dose of flavopiridol, fluorouracil, and leucovorin calcium with or without irinotecan in patients with advanced malignancy.~II. Assess the toxic effects of these regimens in these patients. III. Determine the clinical response in patients treated with these regimens.~OUTLINE: This a dose-escalation study of flavopiridol (FLAVO), fluorouracil (5-FU), and irinotecan. Patients are assigned to 1 of 2 groups. Groups I and II are conducted sequentially.~Group I: Patients receive FLAVO IV over 24 hours on day 1 and leucovorin calcium (CF) IV and 5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FLAVO and 5-FU until the maximum tolerated doses (MTD) are determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.~Group II: Once the MTDs for FLAVO and 5-FU are determined, patients receive FLAVO, CF, and 5-FU as in group I plus irinotecan IV over 1.5 hours on day 1. Courses repeat as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the MTD is determined. The MTD is defined as in group I.~Patients are followed at 3 months.~PROJECTED ACCRUAL: A maximum of 57-90 patients will be accrued for this study within 18 months.

Phase I trial to study the effectiveness of combining flavopiridol, fluorouracil, and leucovorin with or without irinotecan in treating patients who have advanced cancer. 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 of gemcitabine and carboplatin in patients with advanced solid tumors. II. Determine the dose-limiting toxic effects of this regimen in these patients. III. Evaluate the pharmacokinetics and pharmacodynamics of this regimen in these patients. IV. Determine the observed responses in these patients receiving this regimen.~OUTLINE: This is a dose-escalation study of gemcitabine. Patients are stratified according to prior therapy (no prior chemotherapy and/or prior radiotherapy to less than 20% of bone marrow vs prior chemotherapy and/or prior radiotherapy to at least 20% of bone marrow). Patients receive carboplatin IV over 30 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-3 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 2 of 3 patients experience dose-limiting toxicity. Patients are followed for survival.~PROJECTED ACCRUAL: A maximum of 18 patients (9 per stratum) 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 carboplatin and gemcitabine in treating patients who have advanced solid tumors.

Exposure assessment and pathway analysis of organophosphate pesticides to low income pregnant women and children living in the Salinas valley of California. Health study investigating neurodevelopment, growth, and asthma in children.

Exposure and health study of pesticide and allergen exposures to pregnant women and children. Intervention study is planned after assessment is completed.

OBJECTIVES: I. Assess the analgesic efficacy of valdecoxib administered in addition to opioid medication in patients with chronic pain due to cancer or prior cancer therapy. II. Assess the safety of this drug in these patients.~OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to baseline average pain intensity score (2-4 vs 5-11). Patients are randomized to 1 of 2 treatment arms. Patients undergo a pretreatment period of 3-14 days to determine daily dose of sustained release and immediate release opioid medications required to adequately control pain with tolerable side effects. Arm I: Patients receive oral valdecoxib twice daily in addition to opioid medications. Arm II: Patients receive oral placebo twice daily in addition to opioid medications. Treatment continues for a maximum of 12 weeks in the absence of inadequate pain control or unacceptable toxicity. Patients record daily pain assessments and total daily opioid consumption. Patients also are contacted by telephone weekly for assessment of pain, opioid use, and adverse effects.~PROJECTED ACCRUAL: A maximum of 260 patients will be accrued for this study.

RATIONALE: Valdecoxib may be effective in relieving chronic pain in cancer patients. It is not yet known if valdecoxib is effective in treating chronic pain.~PURPOSE: Randomized clinical trial to study the effectiveness of valdecoxib in relieving chronic pain in cancer patients.

OBJECTIVES: I. Determine whether daily supplementation with selenium significantly reduces total cancer incidence and site-specific cancer incidence in the general population. II. Determine whether this regimen has a beneficial effect on mood.~OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Participants are stratified according to age (60-64 vs 65-69 vs 70-74). Participants are randomized to one of four arms. Arm I: Participants receive oral placebo once daily. Arm II: Participants receive low-dose oral selenium once daily. Arm III: Participants receive moderate-dose oral selenium once daily. Arm IV: Participants receive high-dose oral selenium once daily. Treatment in all arms continues for up to 2 years in the absence of unacceptable side effects or diagnosis of cancer.~PROJECTED ACCRUAL: A total of 510 patients (170 per stratum) will be accrued for this study within 9-12 months.

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. Selenium may be effective in preventing cancer. It is not yet known which dose of selenium may be most effective in preventing cancer.~PURPOSE: Randomized pilot study to determine the effectiveness of selenium in preventing cancer in healthy people.

PRIMARY OBJECTIVES:~I. Determine the maximum tolerated dose and recommended phase II dose of BMS-214662 when combined with trastuzumab (Herceptin) in patients with advanced solid tumors.~II. Determine the dose-limiting toxic effects of this regimen in these patients.~SECONDARY OBJECTIVES:~I. Determine the pharmacokinetics of this regimen in these patients. Ii. Determine, in a preliminary manner, the antitumor activity of this regimen in these patients.~OUTLINE: This is a dose-escalation study of BMS-214662.~Patients receive BMS-214662 IV over 1 hour on days 2, 8, 15, and 22 and trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days 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 preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with BMS-214662 and trastuzumab at the recommended phase II dose.~PROJECTED ACCRUAL: A total of 3-28 patients will be accrued for this study.

Phase I trial to study the effectiveness of BMS-214662 plus trastuzumab in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells

OBJECTIVES:~Determine the antitumor cytostatic activity of gefitinib, in terms of 6-month progression-free survival, in patients with persistent or recurrent ovarian epithelial or primary peritoneal carcinoma.~Determine the nature and degree of toxicity in patients treated with this drug.~Determine the partial and complete response rates in patients treated with this drug.~Determine the duration of progression-free and overall survival in patients treated with this drug.~OUTLINE: This is a multicenter study.~Patients receive oral gefitinib once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.~PROJECTED ACCRUAL: Approximately 22-60 patients will be accrued for this study within 1-2 years.

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and may slow the growth of ovarian epithelial cancer or primary peritoneal cancer.~PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have recurrent or persistent ovarian epithelial cancer or primary peritoneal cancer.

OBJECTIVES:~Determine the antitumor activity of paclitaxel in patients with recurrent or persistent platinum- and paclitaxel-resistant ovarian epithelial or primary peritoneal cancer.~Determine the nature and degree of toxicity of this drug in these patients.~OUTLINE: Patients receive paclitaxel IV over 1 hour once weekly for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.~Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.~PROJECTED ACCRUAL: Approximately 19-51 patients will be accrued for this study within 6-12 months.

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 paclitaxel in treating patients who have recurrent or persistent ovarian epithelial cancer or primary peritoneal cancer.

OBJECTIVES:~Determine the maximum tolerated dose of cisplatin when administered with 3-AP in patients with advanced cancer.~Determine the toxic effects of this regimen in these patients.~Determine the antitumor responses in patients treated with this regimen.~OUTLINE: This is a dose-escalation study of cisplatin.~Patients receive 3-AP IV over 2 hours on days 1-4 and cisplatin IV over 1 hour on days 2 and 3. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of cisplatin 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: A total of 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 trial to study the effectiveness of combining 3-AP with cisplatin in treating patients who have advanced cancer.

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The purpose of this study is to evaluate the effects of a common herbal remedy, St. John's Wort, on the effectiveness of birth control pills. St. John's Wort has recently been shown to increase metabolism of some drugs. If it could increase metabolism of oral contraceptives as well, it may increase the risk of contraceptive failure and unintended pregnancy. Study participants will be evaluated for risk of ovulation on oral contraceptives before and during simultaneous therapy with St. John's Wort.

OBJECTIVES:~Determine whether there is a relationship between the pharmacokinetic characteristics of irinotecan and aging in patients with non-hematologic malignancies.~Determine whether there is a relationship between the toxic effects of this drug and aging in these patients.~Determine whether the relationship between genotype (UGT1A1, CYP3A, and other relevant genes) and phenotype (pharmacokinetics, toxicity) is affected by aging in these patients treated with this drug.~Analyze data collected on the co-morbid conditions and concurrent medications in these patients treated with this drug.~OUTLINE: This is a multicenter study. Patients are stratified according to age (18 to 55 vs 70 and over).~Patients receive irinotecan IV over 90 minutes once weekly for 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.~Patients are followed for survival.~PROJECTED ACCRUAL: A total of 140 patients (70 per stratum) will be accrued for this study within 3.5 years.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Aging may affect the way these drugs work.~PURPOSE: Phase I trial to determine the relationship between aging and the effectiveness of irinotecan in treating patients who have solid tumors.

Background:~-This protocol will provide a means for screening potential candidates for NCI Radiation Oncology Branch (ROB) protocols.~Objectives:~-To permit evaluation of patients referred to the NCI Radiation Oncology Branch in order to identify individuals who will be suitable candidates for Radiation Oncology Branch clinical research protocols.~Eligibility:~-Patients suspected of having, or with biopsy proven malignant disease or patients with a benign condition for whom radiotherapy is a potential treatment.~Design:~-This is a screening protocol. No investigational treatments will be administered on this protocol.

Background:~-This protocol will provide a means for screening potential candidates for NCI Radiation Oncology Branch (ROB) protocols.~Objectives:~-To permit evaluation of patients referred to the NCI Radiation Oncology Branch in order to identify individuals who will be suitable candidates for Radiation Oncology Branch clinical research protocols.~Eligibility:~-Patients suspected of having, or with biopsy proven malignant disease or patients with a benign condition for whom radiotherapy is a potential treatment.~Design:~-This is a screening protocol. No investigational treatments will be administered on this protocol.

This study evaluates a system of remote supervision of laparoscopic surgery. Laparoscopic surgery is performed through small holes in the abdomen called ports. A camera is passed through one port for visualization. Laparoscopic surgery requires an assistant to hold the camera and help the operating surgeon view the surgical field. The assistant camera holder may be a surgeon or a robotic arm. The robotic arm is usually controlled by the operating surgeon. In this study, a robotic arm holding the camera will be used, and will be controlled by a surgeon outside the operating room.

This study evaluates a system of remote supervision of laparoscopic surgery. Laparoscopic surgery is performed through small holes in the abdomen called ports. A camera is passed through one port for visualization. Laparoscopic surgery requires an assistant to hold the camera and help the operating surgeon view the surgical field. The assistant camera holder may be a surgeon or a robotic arm. The robotic arm is usually controlled by the operating surgeon. In this study, a robotic arm holding the camera will be used, and will be controlled by a surgeon outside the operating room.

The utility of PEREGRINE Monte Carlo calculations for radiation treatment planning in a clinical setting will be assessed by comparing results with other fully three-dimensional programs. ROB will investigate PEREGRINE for clinical use at NCI.

The utility of PEREGRINE Monte Carlo calculations for radiation treatment planning in a clinical setting will be assessed by comparing results with other fully three-dimensional programs. ROB will investigate PEREGRINE for clinical use at NCI in collaboration with Lawrence Livermore National Laboratory (LLNL).

OBJECTIVES:~Determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase II dose of XK469 in patients with advanced solid tumors.~Determine the safety of this drug in these patients.~Determine the pharmacokinetics of this drug in these patients.~Determine, preliminarily, any anti-tumor activity of this drug in these patients.~Determine the drug metabolism, drug interaction potential, molecular and cellular predictors of efficacy and toxicity, and clinical confirmation of molecular responses in patients treated with this drug.~OUTLINE: This is a dose-escalation study.~Patients receive XK469 IV over 20 minutes on days 1-5. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of XK469 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of the first 6 patients experience dose-limiting toxicity.~Once the MTD is determined, up to 15 patients are treated at that dose. Patients in the expanded MTD cohort also receive oral NovaSoy® soybean extract twice daily for the study duration.~Patients are followed every 4 weeks.~PROJECTED ACCRUAL: Approximately 25-40 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.~PURPOSE: Phase I trial to study the effectiveness of XK469 in treating patients who have advanced solid tumors.

PRIMARY OBJECTIVES:~I. Determine the maximum tolerated dose of bortezomib and paclitaxel administered in combination with carboplatin in patients with advanced solid tumors.~II. Compare the tolerability and efficacy of the different sequences of this regimen in these patients.~III. Determine the clinical toxic effects and pharmacokinetics of this regimen in these patients.~IV. Determine, preliminarily, the therapeutic activity of this regimen in these patients.~V. Evaluate p53 accumulation as a marker of PS-341 activity, and the effect of paclitaxel/carboplatin on PS-341 induced accumulation of p53.~VI. Exam the effect of PS-341 on the levels of other proteasome targets, e.g. mdm2, p27, p21, cyclins B, D1,E; IκB and other ubiquitinated proteins in tumor tissue, when available.~OUTLINE: This is a dose-escalation study of bortezomib and paclitaxel. Patients are assigned to 1 of 2 treatment groups.~Group A: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.~Group B: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2.~Treatment in both groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. After 6 courses of paclitaxel and carboplatin, patients with stable or responding disease may continue with bortezomib alone at the discretion of the investigator. Cohorts of 3-6 patients in each group receive escalating doses of bortezomib and paclitaxel 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 3 months.~PROJECTED ACCRUAL: A total of 24-96 patients will be accrued for this study within 25 months.

Phase I trial to study the effectiveness of combining PS-341 and combination chemotherapy in treating patients who have advanced solid tumors. PS-341 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining PS-341 and chemotherapy may kill more tumor cells

The use of herbal medicines in the treatment of various medical and psychiatric conditions has accelerated in the last decade. It has also become evident that herbal medications are being used concomitantly with conventional prescription and over-the-counter medications. However, the systematic evaluation of the potential of these agents to interact with conventional medications has been generally neglected. Compounding this problem is the fact that even single entity herbal products can contain a multitude of naturally occurring chemicals which serve as candidates for potential herb-drug interactions by inhibiting or inducing specific hepatic isozymes. Numerous reports document the importance of pharmacokinetic interactions involving inhibition or induction of the cytochrome P450 (CYP) enzyme system. In this study, the ten most commonly used herbal products in the US will be systematically evaluated for inhibition of CYP 3A4 and 2136, and induction of CYP 3A4. Collectively, these enzyme systems are involved in the metabolism of approximately 80% of all marketed medications.~Participants in this study will receive a single dose of the prescription drug alprazolam and the over-the-counter cough suppressant, dextromethorphan on two occasions. A combination of probe drugs will be given to normal volunteers both in the absence and presence of herbal medications. The plasma and urine concentration of these agents and their respective metabolites will be determined in order to evaluate individual herbal products degree and specificity of enzyme inhibitory or inductive effects.

The purpose of this study is to detect potential herb-drug interactions in volunteers.

Over 60 million Americans use herbal medicines; of these, one-fourth also take prescription drugs. Physicians are often unaware of herbal use and of possible drug/herb interactions in their patients. Ginseng and ginkgo, enhancers of physical and mental performance, are two of the most widely taken herbals. We propose a double-blind, randomized, prospective study of effects of ginseng and ginkgo on 1) disposition of probe drugs, 2) cognitive function, and 3) glutathione-S-transferase (GST) and quinone reductase (NQ01), enzymes implicated in chemoprevention of cancer. Probe drugs will be administered to study effects of herbs on their disposition, not for therapeutic effect. Ideal probes must be safe, well tolerated, have minimal pharmacological effect, and share known metabolic pathways with other clinically used drugs. Medically stable drug-free non-smokers will be enrolled.~During a 4-week single-blind run-in, subjects will be given a 4-drug probe cocktail: caffeine to study cytochrome P4501A2 (CYP1A2), dextromethorphan for CYP2D6, buspirone (and endogenous cortisol) for CHP3A and fexofenadine for P-glycoprotein. Losartan will be given separately for CYP2C9. These enzymes metabolize over 95% of clinically used drugs. Enzyme activities will be determined by assaying appropriate blood and urine specimens for probe drugs and metabolites. Cognitive function will be tested and blood lymphocytes collected for measuring GST and NQ01 activities. Sixty subjects will then be randomly assigned to one of 4 double-blind treatment groups of 15 each: 1) ginseng extract (Ginsana), 2) ginkgo extract (Egb761), 3) both herbs, or 4) matching placebos. Tolerability of herbs will be determined. After 6 to 8 weeks of twice daily treatment with study agents, all effect parameters will be reevaluated: probe drug pharmacokinetics, cognitive function, and GST and NQ01 in blood lymphocytes. Interactions of chronic ginseng and ginkgo with drug-metabolizing pathways and with cognitive function will thus be determined.

This study will assess the effects of ginseng and ginkgo on 1) cognitive function, 2) enzymes that process drugs, and 3) enzymes that may help prevent cancer.

This study will attempt to replicate findings suggesting that visual evoked potentials generated in one human brain (Subject A) by photostimulation can generate a correlated EEG signal in the brain of another human subject (subject B) who is located at a distance (14.5 meters) and who is not visually stimulated.~This project will occur in three stages. First we will identify pairs of subjects who have cross-correlated evoked potentials during photostimulation to Subject A at the p < .01 level of significance. If no pairs can be identified we will continue to enroll and test up to 50 pairs of subjects. If pairs of subjects that demonstrate the phenomenon cannot be identified using this p value by the end of the project time line we will reject the hypothesis that remote transfer of neural energy occurs and report failure to replicate the original study. If we detect greater than or equal to 5 pairs of subjects who meet the criteria we will attempt to replicate in those pairs using a higher criteria of p < .001. If Grinberg-Zylberbaum et al's experiment can be replicated at both stages, the project team will go to stage 3 to investigate the same phenomenon in the identified pairs of human subjects using functional magnetic resonance imaging (fMRI) as a second independent neurophysiological measure of transfer of information between two human brains. We will record fMRIs (occipital, temporal, frontal and parietal) in the remote individual while their counterpart, located in a separate chamber, is receiving light stimulation in an on-off pattern. We will determine if there are statistically significant differences in digitized fMRI during lights on vs. lights off conditions. The main outcome measures for this project will be the binary (yes-no) output from statistical analysis using cross-correlational and z-score testing for the detection of a transferred evoked signal (in both EEG and fMRI experiments) in Subject B. Appropriate controls will be used. If replicated, this study will provide a useful technology and method to quantitatively investigate the characteristics and neural mechanisms of remote effects of mental events. Such experimental methods will assist in the investigation of basic mechanisms involved in mind-body medicine.

The purpose of this study is to determine whether visual evoked potentials generated in one human brain by photostimulation can generate a correlated EEG signal in the brain of another human subject who is located at a distance and who is not visually stimulated.

PRIMARY OBJECTIVES:~I. To determine and compare the feasibility and clinical toxicity of administering rF-B7.1 and rF-TRICOM vaccines to patients with accessible cutaneous, subcutaneous, or lymph node metastatic tumors.~II. To determine and compare the feasibility and clinical toxicity of administering rF-B7.1 and rF-TRICOM vaccines to patients with accessible visceral metastatic tumors.~III. To determine the optimal dose of rF-B7.1 and rF-TRICOM vaccine delivered by intra-tumoral injection.~IV. To compare the clinical responses and safety profile of patients with cutaneous tumors and visceral tumors who receive rF-B7.1 vaccine to similar patients receiving rF-TRICOM vaccine.~SECONDARY OBJECTIVES:~I. To establish evidence of host anti-tumor immune reactivity following intra-lesional vaccine administration and compare any differences between rF-B7.1 and rF-TRICOM in patients with cutaneous tumors and visceral tumors.~II. To evaluate the quality of life during vaccine administration.~OUTLINE: This is a randomized study with dose-escalation component. Patients are stratified according to tumor location (cutaneous, subcutaneous, or lymph node metastases vs visceral metastases). Patients are randomized to 1 of 2 treatment arms.~ARM I: Patients receive rF-B7.1 vaccine intratumorally on day 1.~ARM II: Patients receive fowlpox-TRICOM vaccine intratumorally on day 1.~Treatment in both arms repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive additional courses.~Three patients from the cutaneous disease (CD) stratum are treated at low-dose in each treatment arm. If no more than 1 of 6 patients experience dose-limiting toxicity (DLT), then 6 additional CD patients are randomized to high-dose treatment. If no more than 1 of these 6 patients experience DLT, then 12 patients from the visceral disease (VD) stratum are randomized to low-dose treatment. If no more than 2 of 12 VD patients experience DLT, then the next cohort of 12 VD patients is randomized to high-dose treatment. If 3 of the original 12 VD patients experience DLT, then 6 additional VD patients receive low-dose treatment. If no more than 3 of 18 patients experience DLT, then 12 VD patients receive high-dose treatment.~Quality of life is assessed at baseline, monthly during therapy, and then at the end of therapy.~Patients are followed every 3 months.

Randomized phase I trial to compare the effectiveness of two different vaccines given directly into the tumor in treating patients who have metastatic solid tumors. Vaccines may make the body build an immune response to kill tumor cells. Infusing the vaccine directly into a tumor may cause a stronger immune response and kill more tumor cells. It is not yet known which vaccine may be more effective in treating metastatic solid tumors

The regimen-related toxicities associated with bone marrow transplantation (BMT) can be severe and even life threatening. The overall goal of this randomized controlled pilot study in BMT patients is to determine the effect of relaxation/stress reduction strategies on: (1) the frequency/severity of toxic side effects of marrow ablative chemotherapy, and (2) the timing of immune reconstitution. Substantial literature indicates that music therapy-based interventions are effective in inducing relaxation and also affect immune function by modulating circulating and salivary levels of such agents as cortisol, immunoglobulin A, interleukin-1, natural killer cells, and a variety of other immune system-related substances. Over the past two years, we have provided music therapy-based stress reduction/relaxation interventions to a convenience sample of patients undergoing BMT. Preliminary findings from this pilot feasibility study demonstrate that patients report significantly decreased pain (p< .004) and sense of nausea (p < .001) following an intervention. Average time-to-engraftment was 13.5 (+/- 2.85) days as compared to 15.5 (+/- 4.40) days (p < .O1) for a group of historical controls matched on diagnosis, type of transplant, conditioning regimen, date of transplant, age, and gender. Although highly promising, our data are limited by lack of randomization, an appropriate control condition, measurement of psychologic factors known to influence outcome in BMT, and systematic monitoring of early phase markers of immune reconstitution that could help explain the phenomena we have observed. This proposal corrects these shortcomings and especially highlights the potential mediational effect of cytokine release on regimen-related toxicities and the timing of immune reconstitution.

The purpose of this study is to determine the effects of music therapy-based relaxation stress/reduction strategies on the frequency/severity of toxic side-effects of marrow ablative chemotherapy and the timing of immune reconstitution in patients undergoing bone marrow/stem cell transplantation.

Intervention: (1) Cognitive stratification (obtained by a test of cognitive ability, followed by a tailored IC process); (2) Pre-recruitment video (a patient-activation video designed to prevent several common misconceptions; (3) Provide prospective research volunteers with a sense of the purpose and methods of controlled research); and (4) Evaluation of the informed consent process using the Brief Informed Consent Evaluation Protocol (BICEP) developed in EQUIC-DP.~Primary Hypothesis: The validity of informed consent can be improved, as measured by an independent interview of patients (BICEP), by at least one of three interventions described above.~Primary Outcomes: The quality of the informed consent process, as measured by the BICEP (Brief Informed Consent Evaluation Protocol). The BICEP also offers a method to certify informed consent in routine use.~Study Abstract: Customized Consent will develop and test an innovative, supplemental method of disclosing information to patients in the informed consent process. This disclosure strategy is intended to increase patients' understanding and satisfaction with the consent process. This study has two goals:~to evaluate the effectiveness of an intervention to improve comprehension during informed consent; and~to identify those patients for whom this intervention is most effective.~The primary goal of EQUIC-CC is to determine whether an intervention, added to usual procedures for obtaining informed consent, is able to improve comprehension. The second goal of EQUIC-CC is to identify those patients for whom an augmented consent intervention is most effective, as well as to determine which subgroups of patients, if any, are most likely to benefit from visual information added to the usual disclosure phase of obtaining informed consent.

Patients in 'parent' cooperative study projects are interviewed about their experiences in the informed consent process.

Intervention: Immediately after giving informed consent for the parent study and before randomization, research subjects will be asked for consent to participate in EQUIC-DP.~The parent-study staff will provide the research subject with privacy and place a call to the coordinating center. Staff (at the EQUIC coordinating center), who will be administering the Brief Informed Consent Evaluation Protocol (BICEP) to the research subject, will introduce themselves. Then, the subject will be interviewed using a BICEP structured assessment questionnaire of approximately 12-20 open ended questions, aimed at determining the success and validity of the informed consent process of the parent study. The results of the interviews will be used to fine-tune and adjust both the process of assessing informed consent in this manner as well as the questionnaire itself.~Primary Hypothesis: Enhancing the Quality of Informed Consent Development Phase (EQUIC-DP) is a pilot and instrument-development study that will be used as the base for a VA Cooperative Studies Program-wide initiative on informed consent, called EQUIC (Enhancing the Quality of Informed Consent). EQUIC-DP has as its primary aim the field testing and iterative improvement of a method for measuring the success of an informed consent encounter with a patient-subject.~Primary Outcomes: The quality of the informed consent process, as measured by the BICEP (Brief Informed Consent Evaluation Protocol). The BICEP also offers a method to certify informed consent in routine use.~Study Abstract: Practitioners of clinical trials have a responsibility to ensure that patients participation in research is informed and voluntary. This implies that we should continuously strive to improve the effectiveness of methods for informing prospective research volunteers about experimental studies, thereby enhancing the likelihood that their interests are respected. Innovations in informed consent should be tested in realistic contexts (i.e., in clinical trials) and when appropriate with randomization at the first opportunity. In this proposed project we take efforts to improve the quality of informed consent, based on experimentation with informed consent in ongoing clinical trials in the VA Cooperative Studies Program. The CSP is uniquely situated to serve as a testing ground for informed consent, not only because of concerns for enhancing consent for human experimentation, but also because of the centralized coordination of wide variety of clinical studies representing an extraordinary range of patient capacities and vulnerabilities. Moreover, such an effort is a special responsibility of the VA given the profound trust placed in the research enterprise by veterans.

Patients in 'parent' cooperative studies projects are interviewed about their experiences in the informed consent process.

Intervention: Self-Monitoring Questionnaire (a questionnaire relating to the process of IC self-administered by study coordinators) and evaluation of the informed consent process using the Brief Informed Consent Evaluation Protocol (BICEP) developed during the EQUIC-DP phase.~Primary Hypothesis: We hypothesize that by focusing attention on what may have become a routinized process, the quality of the IC encounter will be enhanced. We will evaluate the success of this intervention by having the patient-subject complete a telephone questionnaire, the BICEP (Brief Informed Consent Evaluation Protocol), after the IC process is completed.~Primary Outcomes: The quality of the informed consent process, as measured by the BICEP (Brief Informed Consent Evaluation Protocol). The BICEP also offers a method to certify informed consent in routine use.~Study Abstract: Enhancing the Quality of Informed Consent Self-Monitoring (EQUIC-SM) is one component of a VA Cooperative Studies Program-wide initiative on informed consent (EQUIC). Its objective is the field testing and iterative improvement of one intervention in the informed consent (IC) process, self monitoring. Self-monitoring involves having the person obtaining IC complete a Self-Monitoring Questionnaire, or SMQ after the IC encounter with a patient-subject being recruited for a participating study. We conceive of the SMQ as an activation device which prompts the person obtaining IC to monitor how he/she conducts the IC encounter. RESEARCH DESIGN: EQUIC-SM will be conducted in conjunction with participating clinical trials of the VA CSP at multiple VAs throughout the country. Patient-subjects will be recruited from among participants in these parent studies. Parent studies will be randomized to SM protocol or to control sites.~METHODOLOGY: Patient-subjects will be informed about EQUIC-SM at the time that they are first presented with information about the parent study. The person obtaining consent will use a scripted description of EQUIC-SM. If the subject agrees, verbal consent for EQUIC-SM will be obtained. The same parent study informed consent process will be used for both the SM protocol and control arms of EQUIC-SM; however in the SM protocol arm, the person obtaining consent will complete the SMQ after the IC process. In both arms, patient-subjects will be asked to complete the BICEP interview after the parent study IC process is completed. FINDINGS: Investigators will use the results of EQUIC-SM to assess the value of the self-monitoring technique in improving the quality of informed consent. The premise is that focusing the attention of the person obtaining informed consent on the IC process will enhance the quality of the IC encounter, and thus of the informed consent obtained.~SIGNIFICANCE: Practitioners of clinical trials have a responsibility to ensure that patients participation in research be informed and voluntary. This responsibility implies that we should strive continuously to improve the effectiveness of methods for informing prospective research volunteers about experimental studies, thereby enhancing the protection of their interests. If the self-monitoring technique tested in EQUIC-SM proves to enhance the quality of informed consent, this technique may be adapted for wider use in conducting clinical trials, thus representing an important step towards this goal.

Patients in 'parent' cooperative studies projects are interviewed about their experiences in the informed consent process.

Alternative therapies and herbal remedies are increasingly recognized as having therapeutic value, and as many as 42% adults use some form of complementary and alternative medicine (CAM). The prevalence of CAM use among adolescents is not known. Questions remain about the safety and efficacy of some CAM therapies, and how to best facilitate communication about alternative medicine between patients and clinicians. Research with adults shows that most do not reveal their use of alternative therapies to their providers. Adolescence is a time of experimentation and the beginning of a shift from depending upon parents to taking responsibility for one's own care. Thus, the health practices begun in adolescence have an impact into adulthood. However, none of the current guidelines for the provision of care to adolescents advise asking about complementary or alternative medicine use. Finally, adolescents are exposed to increasing coverage of CAM in the media, and on the internet. The specific aims of this study are to: 1) determine the prevalence of complementary and alternative medicine use among a representative sample of adolescents, 2) describe the range of therapies adolescents use, and where they are procured, 3) describe adolescent and clinician factors that are associated with communication between adolescents and their providers about complementary and alternative medicine, and 4) describe adolescents' exposure to information about CAM from sources such as parents, providers, and the media, and how this impacts CAM use. We propose a cross sectional random digit dial telephone survey of 1200 adolescents in Monroe County, NY. Our findings will allow us to understand how adolescents use alternative medicine. Additionally, since alternative therapies can have potentially serious side-effects or drug interactions, insight into how and when alternative medicine use is disclosed may help clinicians provide better care to adolescents.

The purpose of this study is to help improve our understanding of when and why adolescents decide to use alternative and complimentary medicines, and to understand factors that lead to better communication between youth and their clinicians.

Although vitamin D is known to be stored in fat tissue, researchers are not sure about the role that fat tissue plays in vitamin D metabolism. This study will help develop the methodology necessary to further investigate the role of fat tissue in vitamin D metabolism and will assess the relationship between levels of vitamin D in fat tissue and in blood. 50 subjects who are referred for gastric bypass surgery will be enrolled in this study. Subjects will complete questionnaires about their medical history, travel history and food intake. Prior to or during surgery, subjects will be asked to provide a blood sample for selected chemistries related to vitamin D metabolism. During gastric bypass surgery, the surgeon will collect small pieces of fat tissue from the fat under the skin and within the abdomen by surgical biopsy. These samples will be used to refine the methodology for determining the levels of vitamin D in blood and fat tissue and for comparing levels of vitamin D in various tissues.

Vitamin D is a fat soluble vitamin that has important effects on calcium (including absorption of calcium from the diet) and bone metabolism. Vitamin D is known to be stored in fat tissue, and it is also present in the circulation. The purpose of this study is to investigate the relationship between levels of vitamin D in fat tissue and in blood.

Stress is an inherent part of the experience for the neonate who is critically ill and unstable during the initial days in the Neonatal Intensive Care Unit (NICU). Individualized developmentally appropriate nursing care is standard of care (SOC) and provides significant reduction in stressful stimulation. Developmentally appropriate, nurturing stimulation is often lacking. Touch is critical in development of neonatal self-regulation. Healing Touch (HT), a gentle touch and energy healing therapy, is proposed to ameliorate stress and enhance regulatory system development. This R21 feasibility study will involve 40 critically-ill neonates on admission to the NICU, in a parallel, randomized controlled trial, single blind design of 2 groups (N=20 each). In each day for a total of 7 days, each subject will have 2 study conditions: a significant, routinely-occurring, specified stressor followed immediately by either HT+SOC or SOC alone. The treated group will have HT + SOC following a stressor for one study condition and SOC alone for the second study condition; the SOC group will have only SOC for both study conditions. This design allows the treated group to be paired to its own control on each day. During each study condition, markers of stress response will be collected: physiological [heart rate (HR), respiratory rate (RR), oxygen saturation (Sa02) and respiratory sinus arrhythmia (RSA) for cardiac vagal tone (Vna)] and behavioral [Brazelton states 1-6 and cues (self-regulatory and stress) per Bigsby]. The primary hypotheses (all in comparison to SOC alone) are: a) HT will result in improved stress recovery within each study condition, reflected by HR, RR, and Sa02;.b) HT will result in an accumulative improvement in the stress response from day 1-7, reflected by HR, RR and Sa02; c) In infants > 30 weeks gestation, HT will result in + _ improved stress response within each study condition, reflected by increased amplitude of RSA and increased cardiac vagal tone (Vna), or stress reactivity; and d) In infants > 30 weeks gestation, HT will result in an accumulative + _ improvement in the stress response from day 1-7, reflected by increased amplitude of RSA and increased cardiac vagal tone (Vna) both in stress reactivity (measured during the stress response) and in stress vulnerability (measured during sleep). Secondary hypotheses are: a) HT will result in improved neonatal behavioral state and cues during stress recovery within each study condition, as compared with standard of care alone; b) HT will result in accumulative improvement in behavior from day 1-7, during the stress response, as reflected by decrease in stress cues, increased self-regulatory cues, more relaxed behavioral state or decreased frequency of state change. Data analysis will be done using comparison measures [paired, grouped and multiple T-tests]. To assess the data longitudinally, a general linear mixed model will be used; [repeated measures analysis of variance and GEE model]. This study will begin our research in enhancement of neonatal regulatory system development and response to stress and will lay a foundation for larger scale prospective effectiveness and mechanism studies.

The purpose of this project is to evaluate whether or not Healing Touch therapy (HT) helps to treat the stress of babies in the Neonatal Intensive Care Unit (NICU). Healing Touch is a gentle use of human touch - a light, soft placement without moving of the HT therapist's hand on a baby's body - and energy to create balance and relaxation. The goal of HT treatment is to help babies rest better, have less pain and discomfort and to heal more quickly. Healing Touch works along with all the treatments and medicines babies receive as part of ordinary care in the NICU.

Psychosocial interventions, especially supportive-expressive group therapies, have been associated with significant improvements in health status, quality of life and coping behaviors, in patients with cancer. The purpose of the proposed pilot research study is to investigate a newly developed group therapy for cancer patients, MBAT. This proposed, randomized, controlled study follows a successful preliminary investigation of MBAT conducted at Thomas Jefferson University Hospital. MBAT integrates known benefits of art therapy, group therapy, and mindfulness-based stress reduction. Each of these fundamentally different modalities has documented usefulness in the treatment of cancer patients. The multi-modal approach is designed to enhance both the supportive and expressive aspects of the group experience. The study will be done with 96 patients who have a variety of cancer types. Participants will be matched for age and assigned randomly to either the MBAT experimental group or a non-intervention control group. Both groups will continue to receive their usual oncologic/medical care. The MBAT program consists of eight weekly meetings of two and one half-hours in length. At the end of the eight weeks, participants in the control group will be crossed over to the experimental intervention arm for an additional eight weeks. Participants will be assessed pre- and post-intervention on measures of health-related quality of life, psychological distress, and coping, using standardized outcome instruments (SF-36, SCL-90-R and COPE). Our long-term goal is to collect sufficient data to determine the overall efficacy of this promising intervention and to identify which patients are particularly likely to benefit from MBAT.

The purpose of this study is to determine whether cancer patients who receive the mindfulness-based art therapy (MBAT) program demonstrate improvement in health-related quality of life, a reduction in stress-related symptoms, and enhanced coping responses.

This is a prospective randomized, double-blind, placebo controlled, parallel group, Phase 2 study. Subjects meeting selection criteria will be randomly assigned to receive 12 weeks twice daily (BID) dosing with FK614 or placebo. Enrollment for this study will be approximately 200 patients.

The purpose of the study is to assess the safety and efficacy of FK614 in type 2 diabetic subjects receiving sulfonylurea (SU) monotherapy.

OBJECTIVES:~Develop and test a pain assessment and management system for people with cancer (PAMS-PC).~Obtain feedback from patients with non-hematologic malignancies on the proposed features of the system and its usability and effectiveness.~OUTLINE: This is a multicenter study. The study contains 3 parts. Patients in part II are assigned to 1 of 2 assessment groups.~Part I: Patients participate in a focus interview by telephone over approximately 45 minutes. The interview includes discussion of beliefs and concerns regarding pain and its management, strategies used by the patient for managing pain, the features of the proposed pain assessment and management system for people with cancer (PAMS-PC), and reactions of the patients to each proposed component of the system.~Part II:~Group A: Patients participate in an assessment session over approximately 90 minutes, comprising completion of a questionnaire followed by use of a test version of the PAMS-PC.~Group B: Patients use the PAMS-PC first followed by completion of the questionnaire.~Thirty patients are then randomly selected from the 2 groups to repeat use of the PAMS-PC 3 hours after the initial assessment.~Part III: Patients participate in a patient acceptance test over 30-60 minutes, in which patients test the demo version of the system, complete an evaluation questionnaire, and provide feedback by telephone.~PROJECTED ACCRUAL: A total of 180 patients (10 for part I, 150 (75 per group) for part II, and 20 for part III) will be accrued for this study.

RATIONALE: A pain assessment and management system for people with cancer may help doctors accurately assess and plan more effective pain treatment for patients who have cancer.~PURPOSE: Clinical trial to determine the effectiveness of a pain assessment and management system in improving pain management in patients who have nonhematologic cancer.

OBJECTIVES:~Determine the relationship between UGT1A1 genotypes and drug pharmacokinetics and occurrence of gastrointestinal toxicity in cancer patients previously treated with flavopiridol on protocol NCI-97-C-0171C.~OUTLINE: Genomic DNA from pre-existing samples of serum or plasma from each patient is analyzed for UGT1A1 gene by polymerase chain reaction and DNA sequencing. Results are then analyzed for a possible association between UGT1A1 genotypic variation and susceptibility to flavopiridol.~Patients do not receive the results of the genetic testing, and the results do not influence the type or duration of treatment.~PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

RATIONALE: Genetic testing for a specific enzyme may help doctors determine whether side effects from or response to chemotherapy are related to a person's genetic makeup.~PURPOSE: Genetic trial to determine whether different forms of the UGT1A1 gene are related to the body's ability to break down drugs and to the gastrointestinal side effects seen in patients previously treated with flavopiridol.

This application is a continuation of an epidemiologic study that investigates the effect of socio-economic disadvantage and neighborhood conditions on disability in older blacks and whites. The proposed project takes place in the context of a population-based, longitudinal study of persons aged 65 years and over who live in a geographically defined, urban, biracial community area in Chicago. During the initial funding period, we have successfully collected yearly disability outcome data, and detailed information on neighborhood conditions using self-report instruments and a systematic neighborhood survey of study area.~The first overall goal of this continuation is to determine the relative contribution and specific nature of the neighborhood conditions that are associated with disability in older adults. The second overall goal is to determine the biological mechanisms through which neighborhood conditions lead to increased disability, focusing specifically on hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, via salivary cortisol, and inflammatory processes, via interleukin-6 (IL-6) and C-reactive protein (CRP), obtained from blood samples. To accomplish these goals, we propose to continue yearly collection of disability outcome data and obtain blood samples and salivary cortisol from over 7,000 participants. These data will be integrated with a rich set of existing data on personal characteristics, health conditions, and neighborhood factors to test of series of specific hypotheses related to the overall goals.~Disability is a common and highly prevalent consequence of age-related chronic diseases, and a critical indicator of overall health among older people. Prevention of disability is essential to improve the lives of older people and reduce health care costs. The proposed work will contribute to a better understanding of the specific neighborhood conditions that are associated with increased disability, laying the foundation for more effective policies to prevent disability in future generations of older adults.

The overall goal of the proposed project is to examine the reasons for the higher levels of disability in older people of lower socio-economic status.

In this study, patients will receive a single dose of oral valacyclovir. Blood samples will be drawn to evaluate the pharmacology (how the body handles the drug). Blood samples (less than one teaspoon each) will be obtained before receiving the drug and at 0.5, 1, 1.5, 2, 5, 6, and 8 hours after receiving the drug. The total amount of blood drawn from patients for all blood work including routine blood tests as well as pharmacokinetics will not be greater than 5% of the total blood volume.~We will also have all urine output collected for 8 hours starting at the time patients receive the dose of valacyclovir. A 5cc sample of urine will be collected and analyzed to determine how the body handles the drug at hours 2, 4, 6, and 8.

The purpose of this research is to study the pharmacology (how the body handles this drug) of valacyclovir in children receiving treatment for cancer. This study will last approximately 7 days.

OBJECTIVES:~Determine the maximum tolerated dose of fluorouracil when given in combination with UCN-01 and leucovorin calcium in patients with metastatic or unresectable solid tumors.~Determine the clinical toxic effects of this regimen in these patients.~Determine the pharmacokinetics of these drugs in these patients.~Correlate, if possible, the pharmacokinetics of these drugs with clinical toxicity in these patients.~Assess the pharmacodynamic effects of these drugs in these patients.~Assess any clinical activity of this regimen in patients with measurable disease.~OUTLINE: This is a dose-escalation study of fluorouracil (5-FU).~Patients receive leucovorin calcium (CF) IV over 2 hours and 5-FU IV (at the midpoint of CF administration) on day 1, followed by UCN-01 IV over 36-72 hours, on weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of 5-FU until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose (RPIID) is defined as the dose preceding the MTD. At least 6 additional patients are treated at the RPIID.~PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 16 months.

RATIONALE: UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining UCN-01 with chemotherapy may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combining UCN-01, fluorouracil, and leucovorin in treating patients who have metastatic or unresectable solid tumors.

OBJECTIVES:~Describe the motivations, perceptions, and expectations of patients enrolled in a phase I clinical trial.~Assess the influence of age, education, and gender upon the perception of these patients.~Compare the difference in perceptions, motivations, and expectations of patients who have previously participated in a phase I clinical trial vs those who have not.~Determine whether patients' perceptions, motivations, and expectations change while enrolled in a phase I clinical trial.~Validate an interviewer-administered tool measuring the perceptions, motivations, and expectations of these patients.~Assess patients' perception of the information they were given while enrolled in a phase I clinical trial.~OUTLINE: Patients are interviewed over the phone to evaluate their perceptions, motivations, and expectations of phase I clinical trials. Patients complete a questionnaire comprising 24 questions over 30-45 minutes. Interviews are conducted within 1 week after enrolling in a phase I clinical trial (prior to the first dose of study agent) and then again 2 months later (or at the time the patient stops treatment). The first 10 patients enrolled complete an additional 6 questions over 15 minutes during the first interview to validate the questionnaire, but do not complete a second interview.~PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study within 1 year.

RATIONALE: Understanding why patients participate in a phase I clinical trial may help doctors plan better treatment for cancer.~PURPOSE: This clinical trial is studying to determine the reasons for participation, perceptions, and expectations of patients receiving treatment for cancer in phase I clinical trials.

PRIMARY OBJECTIVES:~I. To establish the MTD and toxicity profile of oral capecitabine in combination with q 2 weekly intravenous oxaliplatin in patients with advanced malignancies.~SECONDARY OBJECTIVES:~I. To characterize the pharmacokinetic parameters of capecitabine at the recommended phase II dose for combinations of capecitabine, oxaliplatin, 5-fluorouracil, and leucovorin, as well as for the combination of capecitabine and oxaliplatin.~II. To observe for and record any antitumor activity.~OUTLINE: This is a dose-escalation study of capecitabine.~Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil IV on days 1 and 15. Patients also receive oral capecitabine every 8 hours on days 1-2 and 15-16. Leucovorin calcium and fluorouracil administration is held at dose level 4 and above. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

This phase I trial studies the side effects and best dose of capecitabine when given together with oxaliplatin, leucovorin calcium, and fluorouracil in treating patients with advanced cancer that is metastatic or cannot be removed by surgery. 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.

The major objective of the proposed research is to study the impact of early-life exposures to common urban pollutants on neurobehavioral development and asthma in a sample of children living in three low-income, minority communities of New York City (Central Harlem, Washington Heights and the South Bronx). Using a molecular epidemiologic approach with monitoring, biomarkers, and clinical assessments at serial time points, we will extend our study of African-American and Latina urban mothers and children in order to follow the cohort through child age 11 years to assess the longer-term impact of exposures on child health and developmental outcomes.

A molecular epidemiologic study of African American and Hispanic mothers and newborns to investigate the role of common urban pollutants on procarcinogenic and developmental damage.

There is growing concern about adverse developmental effects in infants and young children from prenatal exposure to environmental air pollutants, including polycyclic aromatic hydrocarbons (PAH), particulate matter (PM2.5), and environmental tobacco smoke (ETS). The proposed study combines expertise in molecular epidemiology and biomarkers, state-of- the-art pollutant monitoring techniques, and a strong theoretical framework to guide assessment of the impacts of these pollutants on fetal and child growth and development. The specific aims are: 1. To test the hypothesis that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) adversely affects fetal growth and early childhood growth and development, after controlling for non-PAH components of PM2.5, ETS, nutritional status (essential fatty acids and antioxidants) and other potential confounders; 2. To explore whether non-PAH components of PM2.5, and ETS have an independent effect on birth outcomes and childhood growth and development, after controlling for PAH, and to explore possible interactions between PAH, PM2.5 and ETS; and 3. To estimate the relative contribution of ambient PAH pollution vs. ETS and other indoor PAH sources to a) personal PAH exposure and PAH-DNA adducts and b) impairment of fetal growth and early child development. To achieve these aims, the international team of researchers will carry out a prospective cohort study of 400 nonsmoking pregnant women living in Krakow, Poland, and will follow their newborns for 12 months postnatally. Fetal growth will be assessed at birth by weight, length, head circumference, and size for gestational age. Childhood growth and developmental outcomes will be measured using the Fagan Test and the Bayley Scales. Strengths of the research include the combination of personal inhalation monitoring of PAH and PM2.5 with biomarkers (umbilical cord blood levels of PAH-DNA adducts, cotinine, essential fatty acids, antioxidants and lead) to estimate in utero exposure to the pollutants of interest and potential confounders. The Polish cohort provides a valuable model for study since emissions from coal burning and traffic are relatively high. However, the results will be broadly applicable since exposures to PAH, ETS and PM2.5 during pregnancy are common in virtually all industrialized regions of the world. It is anticipated that this research will provide relevant data to policymakers concerned with protecting the health of young children.

The goal of this study is to examine the effects of in utero and postnatal exposure to environmental pollutants in a cohort of pregnant women and their newborns in Krakow, Poland

OBJECTIVES:~Determine the maximum tolerated dose of suberoylanilide hydroxamic acid in patients with advanced solid tumors or hematologic malignancies.~Evaluate the pharmacokinetic profile of this drug in these patients.~Determine the effects of this drug on absorption in the fasting and non-fasting states in these patients.~Determine any anti-tumor effects of this drug in these patients.~Correlate clinical outcomes with histone acetylation in circulating mononuclear cells and tumor biopsy samples in patients treated with this drug.~OUTLINE: This is a dose-escalation study. Patients are stratified according to disease (solid tumor vs multiple myeloma or lymphoma vs leukemia or myelodysplastic syndromes).~The initial 15-20 patients (in the solid tumor or multiple myeloma or lymphoma stratum) receive suberoylanilide hydroxamic acid (SAHA) IV over 2 hours on day 1 of week 0 and then orally once or twice daily beginning on day 1 of week 1. All remaining patients receive oral SAHA once or twice daily beginning on day 1 of week 1. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.~In each stratum, cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.~Patients are followed monthly for resolution of adverse events.~PROJECTED ACCRUAL: A maximum of 114 patients (42 with solid tumors, 36 with lymphoma or multiple myeloma, and 36 with leukemia or myelodysplastic syndromes) will be accrued for this study within 1 year.

RATIONALE: Suberoylanilide hydroxamic acid may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.~PURPOSE: Phase I trial to study the effectiveness of suberoylanilide hydroxamic acid in treating patients who have advanced cancer.

OBJECTIVES:~Determine the scale structure, reliability, and validity of the QLQ-SAT32 patient satisfaction module in assessing the perception of the quality of care received in hospitals by patients with cancer.~Determine the success of the QLQ-SAT32 patient satisfaction module when used with the QLQ-C30 core quality of life questionnaire, in terms of expanding on quality of life evaluation or providing information on treatment acceptability or preference of these patients.~OUTLINE: This is a descriptive, multicenter study. Patients are stratified according to age (18 to 49 vs 50 and over) and the cancer therapy received in hospital (surgery vs chemotherapy).~Patients in all strata receive the QLQ-SAT32 and QLQ-C30 questionnaires, a debriefing questionnaire, and the Oberst patient satisfaction visual analog scale prior to hospital discharge. Patients complete the materials at home within 7 days of discharge. A group of 100 patients have a repeat QLQ-SAT32 module mailed to them to be completed within 7 days of receipt of first questionnaire.~PROJECTED ACCRUAL: A total of 640-768 patients (160-192 per stratum) will be accrued for this study.

RATIONALE: Questionnaires may help determine cancer patients' satisfaction with the quality of care they received in the hospital.~PURPOSE: Clinical trial to determine the effectiveness of questionnaires in assessing cancer patients' satisfaction with the quality of care they received in the hospital.

OBJECTIVES:~I. Determine the maximum tolerated dose (MTD) of erlotinib (erlotinib hydrochloride) and irinotecan (irinotecan hydrochloride), in relation to presence or absence of UGT1A1*28 polymorphism, in patients with advanced solid tumors that overexpress epidermal growth factor receptor.~II. Determine the dose-limiting toxicity of these regimens in these patients. III. Determine whether erlotinib alters the disposition of irinotecan using a previously described limited sampling model.~IV. Determine factors that influence the disposition of these drugs, including genetic variation in UGT1A1 and BCRP, in patients treated with these regimens.~V. Determine factors that influence the disposition of these drugs, in terms of tumor BCRP-expression, in tumor samples from patients treated with these drugs at the MTD.~VI. Evaluate the effect of this regimen on epidermal growth factor receptor phosphorylation in these patients.~VII. Assess, preliminarily, any antitumor activity in patients treated with these regimens.~VIII. Correlate, preliminarily, EGFR phosphorylation and/or BCRP -expression with response in tumor samples from these patients.~OUTLINE: This is a dose-escalation study. Patients are stratified according to UGTA1A genotype (all patients regardless of genotype [closed to accrual as of 9/15/04] vs UGT1A1 6/6 genotype vs UGTA1A 6/7 or 7/7 genotype).~Patients receive oral erlotinib hydrochloride daily on days -6 to -1. Patients then receive irinotecan hydrochloride intravenously (IV) over 90 minutes on day 1 and oral erlotinib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients per stratum receive escalating doses of erlotinib hydrochloride and irinotecan hydrochloride until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.~Patients are followed for 3 months.

Phase I trial to study the effectiveness of combining erlotinib hydrochloride with irinotecan hydrochloride in treating patients who have advanced solid tumors. Erlotinib hydrochloride may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib hydrochloride and chemotherapy may kill more tumor cells.

OBJECTIVES:~Determine the maximum tolerated dose of exatecan mesylate in patients with advanced solid tumors and varying degrees of renal dysfunction.~Determine the dose-limiting and non-dose-limiting toxic effects of this drug in these patients.~Determine the effects of renal dysfunction on the plasma pharmacokinetics and pharmacodynamics of this drug in these patients.~Establish a model for dosing this drug in patients with impaired renal function.~OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to severity of renal dysfunction (normal vs mild vs moderate vs severe).~Patients receive exatecan mesylate IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients in each renal dysfunction stratum receive escalating doses of exatecan mesylate 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 in the normal renal function stratum do not undergo dose escalation.~Patients are followed every 3 months.~PROJECTED ACCRUAL: A total of 45 patients (6 normal, 9 mild, 12 moderate, and 18 severe renal dysfunction) will be accrued for this study within 1.5 years.

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 exatecan mesylate in treating patients who have advanced solid tumors and kidney dysfunction.

This is a non-randomized, open-label, Phase I study. A modified Fibonacci dose escalation will be used to determine the MTD for subsequent Phase II trials. Study duration is expected to be 12 to 18 months. Patients with a histological or cytological diagnosis of a solid tumor who have failed standard therapy or for whom no standard therapy exists are enrolled. If there is no dose limiting toxicities and if patients meet the inclusion criteria and have none of the exclusion criteria of the protocol, they will receive further cycles of therapy if there is no evidence of disease progression.

A study for patients who have failed standard therapy. If there is no dose limiting toxicities the patients will receive further cycles of therapy if there is no evidence of disease progression.

Identify the maximum tolerated dose (MTD) and safety of CDC-501 when given in a 6-week cycle in patients with solid tumors that are refractory after standard treatment

To identify the maximum tolerated dose (MTD) and safety of CDC-501 when given in a 6-week cycle in patients with solid tumors that are refractory after standard treatment.

Study participants will receive the following treatment:~Day -5 to -2...Fludarabine 30mg/m2* and CAMPATH** 1H 10mg IV~Day -1.........Day of rest~Day 0..........Stem cell transplant (infusion)~Where possible, patients will receive peripheral blood stem cells. When peripheral stem cells are unavailable (e.g. from some unrelated donor centers) or insufficient, bone marrow will be substituted. If peripheral blood stem cell collection is performed, the donor will be stimulated with G-CSF for 5 days and cells collected and frozen until the stem cell target number is obtained prior to the patient beginning the therapy. If a bone marrow harvest is performed, this will be performed on Day 0 (infusion day). After transplantation, G-CSF 5 micrograms/kg/day will be administered SC from day 7 until granulocytes >1000/ul.~Because CAMPATH-1H infusions will provide a persisting level of antibody over the transplant period, it will contribute to anti-GvHD activity. Additional GVHD prophylaxis will consist of FK506 administered IV via continuous infusion over 24 hours from Day-2 until engraftment or when the patient is able to take by mouth, every 12 hours. This is continued until 6 months post-transplantation. The dose is then tapered every 2 weeks until discontinued. All patients will receive supportive care (prophylaxis for antimicrobial, antiviral, antifungal and Pneumocystis Pneumonia, transfusions of blood products and intravenous gamma globulin and routine laboratory testing of chemistry and complete blood counts) as per Cell and Gene Therapy Standard Operating Procedures (SOP).~Donor engraftment will be evaluated via standard bone marrow studies (cytogenetics/DNA studies for chimerism) on days 30, 60, 100, 180 and 365 post transplantation. If these studies reveal loss of donor cells on two consecutive studies and/or evidence of relapsing disease, the donor will undergo a peripheral blood stem cell harvest via G-CSF stimulation.

To assess the safety, feasibility, and rate of donor engraftment for patients with primary or secondary engraftment failure after treatment with fludarabine and CAMPATH 1H used as a preparative regimen for HLA-identical sibling blood stem cell transplantation (SCT).~To assess the safety, feasibility, and rate of donor engraftment for patients with primary or secondary engraftment failure after treatment with fludarabine and CAMPATH 1H as a preparative regimen for matched unrelated or single antigen mismatched family donor marrow transplantation.

OBJECTIVES:~Determine the maximum tolerated dose of docetaxel when administered with thalidomide in patients with advanced solid tumors, multiple myeloma, and non-Hodgkin's lymphoma.~Determine the dose-limiting toxicity and safety profile of this regimen in these patients.~Determine the plasma pharmacokinetics of this regimen in these patients.~Determine the objective tumor response and prolonged freedom from progression in patients treated with this regimen.~OUTLINE: This is a dose-escalation study.~Patients receive oral thalidomide twice daily and docetaxel IV over 30 minutes once weekly. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of docetaxel and thalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.~PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

RATIONALE: Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining thalidomide with docetaxel may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combining thalidomide with docetaxel in treating patients who have advanced cancer.

OBJECTIVES:~Compare the recovery course of patients with malignancies who undergo standard vs extended recovery preparation after hematopoietic stem cell transplantation.~Compare the efficacy of these recovery preparations in managing rehabilitation needs, including reduced stamina and cognitive limitations, of these patients.~Compare the ability of these recovery preparations to assist patients and caregivers in adjusting to unavoidable fluctuations in caregiver roles and emotions.~Compare the ability of these recovery preparations to assist female patients in managing menopausal symptoms and sexual function changes.~OUTLINE: This is a randomized, multicenter study. Patients are stratified according to gender, type of transplantation (allogeneic vs autologous), ethnicity (Caucasian vs non-Caucasian), total body irradiation (yes vs no), and participating center. Patients are randomized to 1 of 2 supportive care arms.~Patients complete 1 baseline assessment prior to transplant and a second assessment after the transplant, approximately 1 week before returning home.~Arm I (Standard Recovery Preparation): Patients and caregivers receive standard preparation prior to discharge, a booklet of stem cell transplant-related resources and contact information, and the National Cancer Institute-produced publication entitled Facing Forward.~Arm II (Recovery Preparation Intervention): Patients and caregivers receive standard preparation and resource materials as in arm I. Women also receive 10 scheduled telephone appointment sessions, lasting 1 hour each, over the first year after returning home. Men receive 9 scheduled telephone appointment sessions in the same manner as the women. The first 5-6 sessions have a specific topic with a corresponding video. The last 4 calls are booster calls to answer questions, identify new problems, and provide support. Patients with acute problems or problems that cannot be handled through regular sessions are referred to the interdisciplinary recovery triage team. Problems addressed by this team include depression, agitation, cognitive change, fatigue, family disruptions, sexuality, and gynecologic or menopausal difficulties.~Patients are followed at 1 and 2 years.~PROJECTED ACCRUAL: A total of 412 patients and their caregivers (385 patients randomized) will be accrued for this study within 4 years.

RATIONALE: Telephone counseling by trained counselors may enhance the well-being and quality of life of patients who have undergone stem cell transplantation for cancer.~PURPOSE: Randomized clinical trial to compare the effectiveness of standard follow-up care with extended follow-up care in treating patients who have undergone stem cell transplantation for cancer.

OBJECTIVES:~Determine the maximum tolerated dose and the recommended phase II dose of LY317615 and capecitabine in patients with advanced solid tumors.~Determine the safety profile of this regimen in these patients.~Determine the pharmacokinetics of this regimen in these patients.~Determine, preliminarily, the antitumor activity of this regimen in these patients.~Determine the effects of LY317615 on potential angiogenic surrogate markers in these patients.~OUTLINE: This is a dose-escalation study.~Patients receive oral LY317615 daily on days 1-14 (course 1 only). Beginning with course 2, patients receive oral LY317615 daily on days 1-21 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of LY317615 and capecitabine 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 treated at the recommended phase II dose.~Patients are followed at 30 days after the last dose of study drug.~PROJECTED ACCRUAL: A total of 12-36 patients will be accrued for this study.

RATIONALE: LY317615 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth and by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining LY317615 with capecitabine may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combining LY317615 with capecitabine in treating patients who have advanced solid tumors.

OBJECTIVES:~Determine the range of personality traits of patients enrolled in a phase I clinical trial.~Determine these patients' understanding of their medical situation and prognosis.~Determine these patients' understanding of risks and benefits of phase I clinical trials.~Determine these patients' reasons for participating in a phase I clinical trial.~Determine the risk/benefit trade-offs of these patients.~Determine the existential outlook of these patients.~Determine the information gathering nature of these patients.~OUTLINE: This is a multicenter study.~Before beginning phase I clinical trial treatment, patients complete a survey over 30-45 minutes administered by an interviewer. Patients then self-administer the Temperament and Character Inventory assessment over 30 minutes.~PROJECTED ACCRUAL: Approximately 250 patients will be accrued for this study within 6 months.

RATIONALE: Studying individuals who are enrolled in phase I clinical trials may help to improve the way in which clinical trials are conducted.~PURPOSE: This clinical trial is studying patients' personality traits, reasons for participating in the trial, and understanding of their medical situation, prognosis, and risks and benefits of participating in a phase I trial.

This study is a supplement to a parent study which concentrates on the outcomes of homeless mothers who are provided with services and housing. This study will focus on the effects of housing and services on children, who may be the major beneficiaries of such assistance.~Participants are randomly assigned to either receive services and permanent housing or to remain in a homeless shelter without additional assistance. Children and their parents are interviewed separately 3, 9, and 15 months after study entry. The teachers of participating children are surveyed twice during the study.

The purpose of this study is to examine how services and housing provided for homeless families affect the mental health and behavior of homeless children over time.

Youth whose parents smoke cigarettes are at high risk for early initiation of cigarette smoking, and youth who first smoke cigarettes during childhood are at high risk for subsequent addiction to tobacco. Parents influence their children's perceptions of the prevalence of smoking, the acceptability of smoking, the accessibility of cigarettes, and the personal and social consequences of smoking. All parents, including parents who smoke, can engage in anti-smoking socialization, which may lower children's risk of smoking.~Although there are some programs available that are directed at preventing initiation of smoking during childhood, none of these prevention programs engage parents who smoke in altering children's smoking-specific socialization. This study will evaluate a program to change smoking-specific socialization of children in households where parents smoke cigarettes.~Consenting volunteers will be randomly assigned to either treatment (anti-smoking socialization program) or control groups. Parents in the treatment group will participate in the Smoke-free Kids program and receive activity magazines, newsletters, and support calls. Parents in the control group will receive a fact sheet about youth smoking. Parents involved in the study will be assessed through a telephone interview 1 month after completion of the three-month anti-smoking program. Assenting children will complete surveys administered at school at 12, 24, and 36 months after completion of the anti-smoking program. Primary and secondary dependent variables include initiation of cigarette smoking and susceptibility to cigarette smoking by children. The child survey will also assess risk and protective factors.

The purpose of this study is to determine whether an anti-smoking program for parents who smoke will lower the odds that their children will start smoking. The study will evaluate an activity-based program for parents and their children. The program is home-based and uses the mail for program delivery.

More children die violence-related deaths each year than from all natural causes combined. In 2002, the World Health Organization (WHO) reported that 1.6 million people worldwide died from violence in the year 2000; half of these deaths were due to suicides, one-third were due to homicides, and only one-fifth were war related. The United States continues to have the highest number of violence-related deaths of all developed countries.~The WHO has reviewed the effectiveness of worldwide intervention strategies and made recommendations to promote violence prevention throughout the world. Some of the common themes across all countries included: 1) because families play a fundamental role in influencing the propensity for violent behavior, efforts to provide parents with information and strategies for raising nonviolent children are needed; and 2) early interventions to reduce childhood exposure to violence are essential.~In this study, Wake Forest University Health Sciences (WFUHS) and the American Academy of Pediatrics (AAP) will collaborate to evaluate the effectiveness of a pediatric clinician's intervention that has been extensively pilot tested. Pediatric Research in Office Settings (PROS), a program of the AAP, is a national network of practice-based clinicians experienced in research participation. PROS membership consists of more than 697 practices and 1674 clinicians across the country (in 60 AAP Chapters).~This study is being conducted in primary care pediatric clinics across the country that participate in the PROS network.~PROS practices were randomly assigned to either Group 1 (violence prevention intervention) or Group 2 (literacy promotion effort). The study included a total of 137 clinics across the country, 242 practitioners, and 4,890 patients ages 2 to 11 years old. Group 1 providers received a community violence prevention resource worksheet to help them identify community specific assets. Patient families (parent/legal guardian) received tools to help them adhere to provider recommendations. Providers were trained to apply brief techniques of motivational interviewing to help ascertain patient-centered motivation to change violence-related behaviors. Patient families' knowledge, attitudes, and self-reported behaviors were examined prior to the well child exam and at 1 and 6 months after the well child exam. Baseline data were collected in the waiting room; the data forms took 10 minutes to complete. Follow-up telephone interviews were conducted at 1 and 6 months and took 10 minutes to complete.

Violence is one of the major causes of death and injury for children, adolescents, and young adults 10 to 25 years of age. This study will examine the effectiveness of a violence prevention program in pediatricians' offices. The program is designed for families who bring their 2 to 11 year old children in for a well child exam. It focuses on helping parents change behaviors related to the development of violent behavior in children.

This study will conduct an efficacy trial of peer mentoring for a high-risk, predominantly minority population of 9- to 15-year-old youths whose parents are HIV infected. The study will also determine mechanisms (mediating variables) through which peer mentoring improves outcomes for the mentees, for example, consistency and continuity of relationship, teaching/role modeling, emotional support/empathy, advocacy, and behavioral reinforcement. After the conclusion of the efficacy trial, the study will continue through naturalistic longitudinal research for an additional 2 years in order to examine the long-term outcomes of peer mentoring.~Participants are randomized to either the peer mentoring program or a control condition (a recreation program). Surveys are conducted at entry into the study, at 6 months, 1 year, and then annually for 2 years. Youths will also participate in focus groups. The surveys and focus groups will assess the youths' psychological functioning, academic adjustment, alcohol and drug use, HIV risk behaviors, delinquent/violent behaviors, peer relationships, prosocial activities, and coping/problem-solving skills. The study will also evaluate family outcomes, including parent/guardian functioning and improved permanency planning.

This study will evaluate the effectiveness of a peer mentoring program designed for youths ages 9 to 15 whose parents or guardians are HIV infected. The program will focus on the youths' mental health, school performance, alcohol and drug use, personal and social behaviors, and behaviors that might expose them to HIV. The study is expected to enroll predominantly minority youth.

BACKGROUND/RATIONALE:~The Veterans Administration system supports telemedicine (TM) to provide medical consultations between patients and physicians via videoconference. At present, little is known about the impact of such TM consultations on patient-physician communication and related health outcomes. Analyses of in-person (IP) medical encounters have shown that effective patient-physician communication is associated with improved health outcomes.~OBJECTIVE(S):~To determine whether the physical separation between patient and physician required during TM has an affect on patient-physician communication and related outcomes, including patient and physician satisfaction, patient compliance, and patient understanding of medical care.~METHODS:~In this clinical trial, 238 patients were randomized to receive either consultative care at the remote site via TM with a consultant physician located the Milwaukee VA (intervention) OR by an IP consultation with a consultant physician at the Milwaukee VA (control). The same group of consultant physicians provided both IP and TM consultations.~Patients in both study arms had their medical encounter video recorded. We compared patterns and quality of patient-physician communication for the TM and IP encounters, using the Roter Interaction Analysis System. Data on patient and physician satisfaction with the encounter and patients' understanding of their medical problems were collected at the end of each medical encounter. Patient compliance (medication refill behavior) was assessed at 90 days post visit. The frequency of communication behaviors during the TM and IP encounters was compared using the analysis of a Linear Mixed Model. Comparison of patient satisfaction, physician satisfaction, patient compliance, and patient knowledge measures between TM and IP groups were conducted with similar Linear Mixed Models.

The purpose of this study is to determine whether the physical separation between patient and physician required during telemedicine has an affect on physician-patient communication and related outcomes, including patient and physician satisfaction, patient compliance, and patient understanding of medical care.

Background:~We have previously shown that: 1) time tradeoff utilities for current health are high, indicating that patients have a strong will to live; 2) half of patients felt that their life was better now than before they were HIV-infected; and 3) certain non-health-related factors such as spirituality and concern and love for one�s children correlated with health values and a sense that life has improved.~Objectives:~1) To assess health values of veterans and non-veterans with HIV/AIDS; 2) To characterize spirituality in patients with HIV/AIDS; 3) To derive a power function relating health ratings to utilities; and 4) To assess whether society assigns higher values to health states for veterans than for non-veterans.~Methods:~We interviewed 100 representative veterans with HIV/AIDS from the Cincinnati and Pittsburgh VAMCs and, concurrently, 350 non-veterans with HIV/AIDS from Cincinnati and Washington, DC, twice over 12-18 months. The patient questionnaire included clinical and demographic data; health values measures; a question comparing life now with life before being infected with HIV; and measures of health status/health concerns, HIV symptoms, depressive symptoms, spirituality/religion, adherence, social support, self-esteem, and optimism. We also assessed how medical house officers rate and value the health state of a hypothetical patient with congestive heart failure, identified either as a 72-year-old veteran or merely as a 72-year-old male.~Status:~Data collection completed ahead of schedule. Several manuscripts published with others to be submitted soon.

We have previously shown that: 1) time tradeoff utilities for current health are high, indicating that patients have a strong will to live; 2) half of patients felt that their life was better now than before they were HIV-infected; and 3) certain non-health-related factors such as spirituality and concern and love for one�s children correlated with health values and a sense that life has improved.

OBJECTIVES:~Determine the safety and feasibility of administering 1 or 2 courses of vaccination with carcinoembryonic antigen peptide 1-6D (CAP 1-6D)- and CMV pp65 peptide-pulsed autologous dendritic cells in patients with refractory stage IV CEA-expressing malignancies.~Determine the ability of this regimen to induce CAP 1-6D- and CMV pp65-specific T cells in these patients.~Determine the antitumor effect of this regimen, in terms of progression-free survival, of these patients.~OUTLINE: This is an open-label, dose-escalation study.~Patients undergo leukapheresis and collection of peripheral blood mononuclear cells from which dendritic cells (DC) are generated and pulsed with carcinoembryonic antigen peptide 1-6D (CAP 1-6D) and CMV pp65 peptide. Patients are assigned to 1 of 2 vaccination cohorts.~Cohort I: Patients receive vaccination with CAP 1-6D-pulsed DC and CMV pp65 peptide-pulsed DC subcutaneously and intradermally every 3 weeks for a total of 4 vaccinations.~Cohort II: Patients receive vaccinations as in cohort I every 3 weeks for a total of 8 vaccinations.~For both cohorts, a safe dose of the vaccine is defined as the dose at which no more than 1 of 6 patients experiences unacceptable toxicity.~Patients are followed every 3 months for 1 year.~PROJECTED ACCRUAL: A total of 12 patients (6 per cohort) will be accrued for this study within 24 months.

RATIONALE: Vaccines made from a person's white blood cells mixed with peptides may make the body build an immune response to kill cancer cells.~PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with refractory stage IV cancer.

There are 34 million adolescents between the ages of 11 and 17 years old in the United States. Approximately 12% of them are African American. These youths experience earlier pubertal onset and face earlier challenges to participate in sexual activity, and therefore have earlier potential for pregnancy and contraction of sexually transmitted diseases. Experts in adolescent research have recommended developing and implementing new interventions to reduce early sexual activity; these interventions should target middle school-aged youths. The purpose of this study is to evaluate the efficacy of the NIA intervention on intention to engage in early sexual behavior and actual involvement in early sexual behavior in a convenience sample of sixth and seventh grade African American girls.~NIA is a Swahili word that means having a sense of purpose. It is one of the seven principles of Kwanzaa, a holiday that celebrates African Americans' cultural roots in Africa. The intervention was named after a self-development program for African American girls to highlight the intervention's cultural basis.~The study will provide 12 weekly and 5 booster after school didactic sessions; these sessions will teach health promotion and decision making skills to help girls successfully avoid situations where sexual activity is invited. Mothers and daughters will collaborate on homework assignments on puberty, heterosexual relationships, and sexual issues. The study will provide an evening mother-daughter workshop on sexual responsibility and a Baby-Think-It-Over weekend experience for girls using a computerized doll. Finally, the study will provide five Hey Baby! role-play vignettes to teach girls how to avoid heterosexual relationships that may lead to sexual activity.~The NIA intervention will be compared against a usual after-school activity control group of sixth and seventh grade African American girls in two public middle schools in the Pittsburgh Public School system. Participants will be randomly assigned to either the NIA intervention group or the control group. Each participant will be in the study for 1 year. There will be a 12-week main intervention in the fall, a 5-week booster in the spring, and final testing 1 year after study entry. Assessments will be primarily paper and pencil tests of the study's main outcome variables: attitude toward early sexual behavior (ESB); subjective norms (mother, father, peer) toward ESB; intention to engage in ESB; and self-reported ESB. Additionally, there will be knowledge content quizzes after each main intervention or booster session and a written evaluation of the Baby-Think-It-Over weekend.

This study will evaluate the effectiveness of a program designed to prevent early sexual behavior in middle school-aged African American girls.

The purpose of this study is to learn more about the effects of gamma-hydroxybutyric acid by comparing its physiological, behavioral and subjective effects with those of several other drugs.~This trial will be conducted as a double-blind, double-dummy, placebo-controlled, counter-balanced (Latin-square design) crossover study in volunteers with histories of sedative abuse. Volunteers will be recruited through advertising and word-of-mouth.~Volunteers will reside on our residential research unit for the duration of the study and participate in a maximum of 16 experimental sessions. Sessions will be conducted five days a week (Monday through Friday). The primary subjective and behavioral measures will be taken before drug administration and at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours after drug administration.

The purpose of this study is to learn more about the effects of gamma-hydroxybutyric acid (GHB) by comparing its physiological, behavioral and subjective effects with those of several other drugs.

Given the early age of sexual initiation among urban minority youth, interventions aimed at reducing sexual initiation and risky sexual behavior related to HIV and other sexually transmitted infections (STIs) should begin prior to entry into middle school. These interventions should support both students and their parents through the transition to early adolescence. In collaboration with the New York City Public Schools, this study is designed to evaluate strategies to prevent early sexual initiation and its precursors among academically at-risk urban minority boys and girls.~This study will answer two questions: 1) do factors that predict sexual risk taking and its precursors in young adolescence operate similarly in middle childhood; and 2) can interventions shown to be effective in early adolescence be developmentally adapted for middle childhood to delay sexual initiation and its precursors? The study will evaluate the impact of the intervention on mechanisms hypothesized to reduce sexual risk taking and its precursors, including the personal resiliency and social competencies of youth. The study will also collect data on the costs and process of implementation to inform subsequent dissemination.~Participants in this study will be fifth and sixth grade children enrolled in participating public schools in Brooklyn, NY. Participating school communities will be predominantly African American and Latino. In the fall of their fifth and sixth grade years, students and their families are assigned at random to participate in either a parent education group or in a control group. The parent education program, Saving Sex for Later, focuses on the transition from middle childhood to early adolescence, the pressures to engage in risk behaviors (including early sexual initiation and related risks), and peer and parental influences on youth attitudes and behaviors. Those in the control condition receive a classroom health curriculum. In addition, a subgroup in each grade level is assigned to participate in service learning, an educational method in which personal and community values are taught through experience in structured service activities.~Youth will be followed for 12 to 18 months. Surveys will be conducted in the fall of the fifth and sixth grade years and again at a 3-month post intervention follow-up. These surveys will measure youth attitudes and behaviors, including precursors to early sexual initiation and related risk behaviors. Surveys of parents' attitudes and behaviors will also be conducted to supplement information from youth. To assist in interpreting results of the surveys, in-depth qualitative interviews will be conducted with a subgroup of fifth grade youth; these youth will be resurveyed prior to entry into seventh grade.

Working with multiple schools in Brooklyn, NY, this study will develop and evaluate school- and community-based strategies designed to reduce early sexual activity and risky sexual behavior in middle school-aged children. These strategies will focus on parent education, classroom health curriculum, and learning through participation in community service.

Training that involves heavy loads or resistance strengthens muscles. Recent data suggest that substantial voluntary strength gains can be achieved with training involving low resistance and strong mental effort. In contrast, individuals who train with the same low intensity contractions but with low mental effort show no improvement in strength.~This study will evaluate the relationship between mental effort muscle strength improvements by comparing the improvement in muscle strength in participants who have trained with different levels of mental effort. In addition to evaluating muscle strength, this study will also examine the neural mechanisms underlying muscle strength improvements.~Four groups of volunteers (65 years old and over) will participate in a training program directed at elbow-flexor muscles. One group will be trained with an intensity near the level of maximal voluntary contraction (MVC group); a second group will be trained with high mental effort, low muscle intensity contractions (HME group); a third group will be trained with low mental effort, low muscle intensity elbow-flexion contractions (LME group); and the fourth (control) group will not be trained but will participate in the strength tests. Training will be performed every weekday for 12 weeks. Participants will be evaluated by functional MRI (fMRI), EEG-derived motor activity-related cortical potential (MRCP), surface EMG signals, and the MRI T2 relaxation time.~Preliminary analysis of results shows that the HME group gained more than 13% strength, the LME group showed a statistically insignificant 6% change, and the no-practice control group did not show any change in elbow flexor muscle strength. We expect the MVC group to have the highest strength gains among the four groups.

The purpose of this study is to determine the effect of mental effort on improving muscle strength.

The Healthy Youth Places project will test if an intervention strategy that implements school environmental change, with both adult leader and youth participation, will influence and maintain adolescent fruit and vegetable consumption and physical activity.~The study will assess the effects of school environment and curriculum interventions promoting fruit and vegetable (F&V) consumption, physical activity (PA), and their environmental determinants. The project will involve goal-setting and efficacy-building interventions designed to develop the skills and group efficacy of both adult school personnel and students. The adult-based interventions are designed to change the school environments through a school coalition assisted by a local coordinator. The youth interventions involve the participation of students in the processes of building the local health behavior environments and target both school lunch and after-school activity environments.~The project encourages adult and youth participation in the process of planning and implementing environmental change in targeted adolescent physical and social environments (school lunch place, after-school program place). Environmental change is defined as implemented practices, programs, and policies that promote critical elements (connection, autonomy, skill-building, healthy fruit and vegetable and physical activity norms). These critical elements are social environmental processes of behavior change.~Sixteen schools will be randomly assigned to either the experimental or the control (no treatment) condition. The health behavior of adolescents will be assessed during the sixth, seventh, eighth, and ninth grades. Measurement of F&V and PA behaviors are the primary outcomes and will be assessed by self-report and verified by objective measures of school lunch purchases and physical activity monitoring. The impact of the program on personal, environmental, and behavioral determinants of F&V and PA will also be measured.

To reduce the risk for chronic disease, adolescents should eat at least five servings of fruit and vegetables and be physically active daily. This study will implement and evaluate a school-based program to encourage adolescents to achieve and maintain a healthy diet and exercise regimen.

This study will examine the language, reasoning, and social skills used by preschool and elementary school children when they and their parents attempt to understand, conduct, and resolve disputes in everyday family interaction. Families will be given conflict resolution training designed to promote listening and speaking skills that result in more accurate interpersonal and emotional understanding. The training may lower the emotional volatility of family interaction, lower the rate of arguing and fighting between parents and children, increase the rate and frequency of verbal negotiation, and encourage the adoption of conflict strategies that focus on future-oriented behavior and positive outcomes.~A total of 324 working class families, representative of the primary ethnic populations in Chicago (African American, Caucasian, and Mexican American), will be selected for participation. Both parents, one 4- to 6-year-old child, and one 6- to 8-year-old sibling will participate. Single parent families will also be included; the parent will be asked to nominate a second adult or an additional older sibling in place of the second parent.~Each family proceeds through three phases. The initial phase allows assessment of conflict histories, good times, self-appraisals of psychological well-being, affective and social variables that operate within the family, and the family members' ability to discuss and negotiate ongoing problems.~In the second phase, families are randomly assigned to one of three experimental conditions. One group is given conflict resolution training and then participates in a series of tasks that focus on child-parent narration, negotiation, and negotiation assessments. A second group participates in the same tasks without training. A third group undergoes only the negotiation assessments. The effectiveness of the training will be evaluated by experimentally assessing conflict resolution skills before and after training in both home and school contexts.~The third phase is a six-month follow-up visit, during which parents and children are again observed negotiating problems. Psychological well-being and affective feelings are once again assessed. The study ends with a debriefing interview for the parents.~The study consists of 14 study visits. Each member in the family will also have four training sessions. Visits are scheduled 3 to 4 times a month, depending on the family's availability.

This study will evaluate the effectiveness of conflict resolution training for families with preschool and elementary school-aged children.

OBJECTIVES:~Determine the maximum tolerated dose of polyglutamate camptothecin (CT-2106) in patients with advanced malignancies.~Determine the tolerability of this drug in these patients.~Determine the safety of this drug in these patients.~Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.~Determine the disease response in patients treated with this drug.~OUTLINE: This is a dose-escalation, multicenter study.~Patients receive polyglutamate camptothecin (CT-2106) IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive 2 additional courses beyond confirmation of complete response.~Cohorts of 3-6 patients receive escalating doses of CT-2106 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.~PROJECTED ACCRUAL: A total of 12-48 patients will be accrued for this study.

RATIONALE: Drugs used in chemotherapy such as polyglutamate camptothecin may be able to deliver the drug directly to tumor cells while leaving normal cells undamaged.~PURPOSE: Phase I trial to study the effectiveness of polyglutamate camptothecin in treating patients who have advanced cancer.

This study will identify personal, parental, peer, and community factors that predispose children ages 6 to 12 to early initiation of sexual behavior or that foster resilience to sexual risk taking. The study will then evaluate an intervention designed to enhance resilience factors and reduce risk factors among 6- to 12-year-old children. The study will focus on the mother's role in promoting resilience to sexual risk taking.~During the first phase of the study, 300 children and their mothers will be asked to complete a one-time interview that includes an assessment of risk and resilience factors. Information from the interviews will be used to modify an intervention currently being used in another study of parent-adolescent pairs. The modified intervention will then be tested to determine the efficacy of the intervention in reducing risk and enhancing resilience among children in this age group.~In the second phase of the study, 296 children and their mothers will be randomized to either the intervention or control group. All mothers will complete a baseline interview. Mothers in the intervention group will attend 10 group sessions that include short presentations, discussions, media presentations (videotapes), and interactive exercises, including self-assessments, role plays, and games. The group sessions include content and skill development related to parenting, communication, sexuality, peer pressure, and school involvement. Mothers in the control group receive written information on diet and physical activity. The written materials are presented in a self-help format to increase physical activity; a cookbook contains low fat recipes designed especially for African American men and women living in the Atlanta, GA, area.~All participants complete follow-up interviews at 6 and 12 months after the baseline interview. Primary outcomes for mothers include measures of resilience and communication related to sexual issues. For children, outcomes include measures related to possible sexual situations.

The goal of this study is to enhance the mother's role in promoting avoidance of sexual risks and problem behaviors in 6- to 12-year-old children. Consenting mothers will attend a 10-session program designed to enhance the quality of mother-child communication, identify sexual risks, and increase parental monitoring and self-efficacy.

The traditional assumption when fabricating a transtibial amputee (TTA) socket is that the residual limb is not homogeneous in its ability to tolerate load. As a result, prosthetic sockets are currently fabricated by modifying a positive mold to account for this non-homogeneity; these are called rectified sockets. Unrectified sockets retain the shape of the residual limb, except for a distal end pad. Unrectified sockets use an alginate gel method of fabricating that is simpler and less time consuming than the method used to fabricate rectified sockets. This study will compare patient satisfaction and function with rectified and unrectified sockets.~Participants in this study will be randomized to either a recitified socket group or an unrectified socket group. Participants will wear the socket for a minimum of 4 weeks. Participants will then fill out a Prosthesis Evaluation Questionnaire (PEQ). The PEQ quantifies patient satisfaction by evaluating nine validated scales. Functional measures of energy expenditure, kinematics, and ground reaction forces during gait will also be collected. After 4 weeks, participants in the rectified socket group will switch to an unrectified socket and participants in the unrectified socket group will switch to a rectified socket. At the end of 4 weeks with the new socket, participants will once again fill out the PEQ and undergo functional assessment. At the end of study participation, each participant will freely choose the socket they wish to have in their final prosthesis.~Thus far, 10 study participants with unilateral transtibial amputations have been evaluated after randomly wearing both rectified and unrectified sockets for 4 weeks. Results indicated no differences between sockets for gait speed and timing, gait kinematics and kinetics, gait energy expenditure, and Rate of Perceived Exertion (RPE). There were also no differences in the Prosthetic Evaluation Questionnaire. Four participants selected the rectified socket and 6 selected the unrectified socket as their exit socket.

People who have had a leg amputated often choose to use a prosthetic (artificial) leg. This study will evaluate a new method of making prosthetic legs for people who have had an amputation below the knee.