ds4dh/ct-dosing-errors huggingface dataset:
Clinical trial NCT01175148
Conditions: Graft vs Host Disease
Keywords: HSCT HPC HCT BMT lipitor atorvastatin HMG-CoA Reductase Inhibitor Hematopoietic stem cell transplant allogeneic transplant GVHD graft-versus-host-disease Graft vs Host Disease
Sponsor: West Virginia University
Start date: 2010-07-01; Completion date: 2014-12-01
Enrollment: 60 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Atorvastatin for prevention of acute GVHD

Detailed description:
This is a phase II study of atorvastatin for the prophylaxis of acute GVHD in patients undergoing matched-sibling allogeneic HSCT. This study will explore a two-pronged acute GVHD prophylaxis strategy, consisting of pre-treating consenting sibling donors with atorvastatin before stem cell collection, followed by the addition of atorvastatin to methotrexate/tacrolimus-based GVHD prophylaxis.

Arms: arm 1: Atorvastatin calcium (Lipitor) will be administered at dose of 40mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or development of grade 2 GVHD. This is the experimental arm for outcome measures. arm 2: Sibling donors will start taking Atorvastatin calcium (Lipitor) orally at 40mg once daily between 14-28 days before the anticipated first day of apheresis or bone marrow harvest.
Interventions: intervention 1: Atorvastatin calcium (Lipitor)
Intervention descriptions: intervention 1: 40 mg PO daily

Protocol documents:
Clinical trial NCT01176435
Conditions: Albinism
Keywords: Levodopa Albinism Vision
Sponsor: University of Minnesota
Start date: 2010-09-01; Completion date: 2014-12-01
Enrollment: 45 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This project will evaluate the effect of two doses of levodopa (L-DOPA) in a randomized, placebo-controlled, double-masked clinical trial to see if vision can be improved in individuals with albinism. The hypothesis is that providing L-DOPA to the retinas of these individuals may increase melanin pigment production. Increased melanin has previously been shown to be associated with improved vision.

Detailed description:
A group of 45 individuals with the clinical findings of oculocutaneous albinism (OCA) will be randomly assigned to one of 3 treatment groups: treatment with 0.76 mg/kg/d with 25% carbidopa, 0.51 mg/kg/d levodopa with 25% carbidopa \[divided into 3 doses/d), or placebo. Subjects will be between ages 3 and 60 years. Blood will be drawn to determine the mutation(s) in the genes that causes OCA. Primary outcome will be binocular best-corrected visual acuity measured with the EVA. Enrollment and 20 week examination will be complete eye exam with fundus photos. At weeks 5, 10, and 15, exams will include just vital signs and BCVA. At all visits, a review of potential side effects will be conducted. Between visits, subjects will be contacted to determine if any side effects have occurred. The study will remain double masked until the last study examination on the last subject has been performed. At that time, the data will be statistically analyzed and subjects will be informed re: treatment assignment, mutations found, and the study results.

Arms: arm 1: Solution taken orally three times a day. arm 2: Solution taken orally three times a day. arm 3: Solution taken orally three times a day.
Interventions: intervention 1: Levodopa intervention 2: Levodopa intervention 3: Placebo
Intervention descriptions: intervention 1: Solution taken orally three times a day. intervention 2: Solution taken orally three times a day. intervention 3: Solution taken orally three times a day.

Protocol documents:
Clinical trial NCT01188681
Conditions: Chronic Lymphocytic Leukemia (CLL)
Keywords: CLL TRU-016 chronic lymphocytic leukemia relapsed CLL bendamustine
Sponsor: Aptevo Therapeutics
Start date: 2010-09-01; Completion date: 2014-12-01
Enrollment: 79 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of the first part of the study is to determine a safe dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. The objectives of the second part of the study are to compare the safety and efficacy of TRU-016 in combination with bendamustine to bendamustine alone in patients with relapsed CLL.

Detailed description:
This study consisted of two parts. The initial dose escalation stage was a Phase 1b study evaluating the safety and tolerability of two doses of TRU-016 administered in combination with bendamustine to patients with relapsed chronic lymphocytic leukemia (CLL). In the randomized Phase 2 stage of the study, the efficacy and safety of the selected dose of 20 mg/kg TRU-016 combined with bendamustine was compared to bendamustine alone. The pharmacokinetics and pharmacodynamics of TRU-016 and the development of antibodies to TRU-016 were evaluated in both phases of the study.

Arms: arm 1: TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients arm 2: TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients arm 3: TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients arm 4: Bendamustine (70 mg/m2), n = 33 patients
Interventions: intervention 1: TRU-016 and bendamustine intervention 2: Bendamustine intervention 3: 15 mg/kg TRU-016 and bendamustine intervention 4: 20 mg/kg TRU-016 and bendamustine
Intervention descriptions: intervention 1: TRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles intervention 2: Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles intervention 3: TRU-016 at 15 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles intervention 4: TRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles

Protocol documents:
Clinical trial NCT01230307
Conditions: Heart Failure
Keywords: Vitamin D Systolic failure Genomics Biomarkers Exercise Quality of Life
Sponsor: University of Michigan
Start date: 2010-10-01; Completion date: 2014-12-01
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The central objective of this proposal is to establish that vitamin D supplementation in heart failure patients with low vitamin D levels will have improved outcomes compared to placebo. In addition the investigators will also evaluate the role of genetics in regard to vitamin D and heart failure. The investigators will be evaluating what is currently a novel approach of identifying patients with low vitamin D and treating this low vitamin D level. The investigators will be able to evaluate the importance of vitamin D supplementation in these patients and the role of genetics on our defined outcomes.

Detailed description:
Primary Objective To determine how rapid vitamin D supplementation affects biomarkers and submaximal exercise capacity in systolic HF patients with low vitamin D status.

Working Hypothesis 1: HF patients when supplemented with vitamin D for 6 months will have lower measures of inflammation and extracellular-matrix remodeling compared with placebo.

Working Hypothesis 2: HF patients when supplemented with vitamin D for 6 months will have longer 6-minute walk length compared with placebo.

Secondary Objectives To establish a relationship between the CYP2R1 variant and surrogate markers in systolic HF patients.

Working Hypothesis 3: HF patients with the CYP2R1 G allele will have higher measures of inflammation and extracellular-matrix remodeling compared to AA subjects. This relationship will also be seen in subjects with the CYP2R1 TagSNP variants.

Working Hypothesis 4: HF patients with CYP2R1 variant alleles will have shorter 6-minute walk length compared to subjects without these variants.

To genotype HF subjects for the VDR variants and additional tag SNPs, to ascertain the relationship between VDR genetic variation and surrogate markers in systolic HF patients.

Working Hypothesis 5: HF patients with VDR variants will have greater measures of inflammation and extracellular-matrix remodeling compared to subjects without VDR variants.

Working Hypothesis 6: HF patients with VDR variants will have a shorter 6-minute walk length compared to subjects without these variants.

Arms: arm 1: Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months arm 2: A placebo loading dose will be given followed by two placebo tablets daily for 6 months.
Interventions: intervention 1: Vitamin D3 intervention 2: Placebo
Intervention descriptions: intervention 1: Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months intervention 2: A placebo loading dose will be given followed by 2 placebo tablets daily for 6 months.

Protocol documents:
Clinical trial NCT01253369
Conditions: Small Cell Lung Cancer Lung Cancer SCLC
Keywords: pazopanib
Sponsor: Dana-Farber Cancer Institute
Start date: 2010-06-01; Completion date: 2014-12-01
Enrollment: 33 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Pazopanib is a drug that inhibits proteins thought to be important for new blood vessel formation. This drug has been used in other cancer research studies and information from those studies suggests that pazopanib may help block proteins that are important for the growth, invasion, and spread of cancer cells.

Detailed description:
OBJECTIVES:

Primary

\- To determine the progression-free survival rate in participants with relapsed or refractory small cell lung cancer who have received one prior regimen of systemic chemotherapy at 8 weeks

Secondary

* To determine the response rate (as measured by RECIST 1.1 criteria and changes in blood flow/perfusion as measured by perfusion CT)
* To determine median and overall survival
* To characterize the toxicity profile of pazopanib in this patient population.

Exploratory

* To analyze levels of circulating biomarkers from blood and urine samples obtained serially throughout the study and assess the utility of individual or subsets of these proteins to serve as a surrogate marker for treatment effect, treatment efficacy, and for tumor progression
* To measure and investigate the use of monocytes as surrogate markers of angiogenesis inhibition
* To analyze the subject population by identification of intra-tumoral biomarkers (such as c-kit, VEGF receptors, and microvessel density measured in available tumor biopsies) associated with the efficacy, safety and resistance to pazopanib
* To assess the utility of perfusion CT scan in evaluating changes in anti-angiogenic activity as a measure of treatment efficacy

STATISTICAL DESIGN: This study uses a two-stage design to evaluate efficacy of cetuximab based on progression-free rate (PFR) at week 8 defined as complete response (CR), partial response (PR) or stable disease (SD) per RECIST 1.1 criteria. The null and alternative PFR are 30% and 50%. If fewer than 4 patients enrolled in the stage one cohort (n=15 patients) achieve SD or better than accrual would not proceed to stage two (n=15 patients). If 13 or more patients are progression-free of the 30 patients then the null hypothesis will be rejected. The probability that the treatment will be considered promising if the true PFR rate was 30% is 8.4% and 82% if the true PFR rate was 50%.

Arms: arm 1: Pazopanib was given at a dose of 800 mg orally once per day for 28 day cycles (+/- 3 days). Patients received treatment as long as they were receiving clinical benefit.
Interventions: intervention 1: Pazopanib
Intervention descriptions: intervention 1: None

Protocol documents:
Clinical trial NCT01267279
Conditions: Osteoporosis
Sponsor: Spokane Joint Replacement Center
Start date: 2005-01-01; Completion date: 2014-12-01
Enrollment: 51 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In a randomized, double-blind trial, BMD of the operated proximal femur after total hip replacement measured by dual-energy x-ray absorptiometry (DXA) were compared for up to two years in patients receiving IV ZOL 5 mg infusion (n = 27) or placebo (IV saline infusion; n = 24) at two weeks and one year after surgery.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Zoledronic acid intervention 2: Placebo
Intervention descriptions: intervention 1: Zoledronic acid per protocol intervention 2: Placebo

Protocol documents:
Clinical trial NCT01283035
Conditions: Ovarian Sarcoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma
Sponsor: National Cancer Institute (NCI)
Start date: 2011-04-01; Completion date: 2014-12-01
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Akt inhibitor MK2206 is a drug that may stop cancer cells from growing by blocking a protein called protein kinase B (AKT) inside the cell. AKT interacts with other proteins in the cell that are part of the P13K/AKT pathway, a pathway that is know to play a role in the growth of cancer cells. Mutations in P13K or in AKT, or changes in another protein called phosphatase and tensin homolog (PTEN) in this pathway can lead it to become more active than is normal. This study investigates how effective MK-2206 is in treating ovarian, fallopian tube, or primary peritoneal cancer where there are mutations in P13K or AKT or low levels of PTEN.

Detailed description:
PRIMARY OBJECTIVES:

I. To assess the activity of MK-2206 (Akt inhibitor MK2206) in patients with recurrent grade 2 or 3 platinum-resistant high-grade serous ovarian, fallopian tube, or peritoneal cancer, as measured by the frequency of patients experiencing an objective tumor response by Response Evaluation Criteria In Solid Tumors (RECIST) criteria or who survive progression-free for at least 6 months after initiation of therapy.

SECONDARY OBJECTIVES:

I. To assess the duration of progression-free and overall survival following initiation of therapy with MK-2206 in the cohort of patients enrolled on this study.

II. To determine the toxicities of MK-2206, as assessed by the active version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 III. To explore the association between select biomarkers and response to MK-2206 (as assessed by objective tumor response, progression-free survival, and overall survival) IV. To explore the development of feedback loop activation and target inhibition with MK-2206 via analysis of pre-treatment and post-treatment biopsies in select patients enrolled in the trial.

OUTLINE:

Akt inhibitor MK2206 will be taken orally (PO) once a week for four weeks (one cycle). Treatment will continue for as long as a subject is benefiting from the study drug.

During each cycle subjects will have a physical exam, blood samples and an electrocardiogram (EKG) (first 2 cycles). Every 2 cycles a computed tomography (CT) scan or magnetic resonance imaging (MRI) of chest, stomach area, and pelvis will be performed. Optional tumor biopsies may be performed.

Arms: arm 1: Akt inhibitor MK2206 will be taken PO once a week for four weeks (one cycle). Treatment will continue for as long as a subject is benefiting from the study drug.
Interventions: intervention 1: Akt Inhibitor MK2206 intervention 2: Laboratory Biomarker Analysis
Intervention descriptions: intervention 1: Given PO intervention 2: Correlative studies

Protocol documents:
Clinical trial NCT01305655
Conditions: Acute Lymphoblastic Leukemia (ALL)
Keywords: Drug: Glucarpidase
Sponsor: Nordic Society for Pediatric Hematology and Oncology
Start date: 2008-07-01; Completion date: 2014-12-01
Enrollment: 47 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Early intervention in children and adolescents who experience delayed MTX-clearance and renal dysfunction in ALL treatments with the enzyme Glucarpidase which rapidly hydrolyses MTX to non-toxic metabolites to avoid life threatening complications.

Detailed description:
The NOPHO ALL-2008 protocol is a treatment and research protocol that aims to improve the overall outcome of Nordic children and adolescents with ALL in comparison with the ALL-2000 protocol and with the aim to reduce and prevent toxic treatment complications with high-dose methotrexate (HD-MTX).

The specific and primary objectives of the randomized study is:

1. Early intervention in children and adolescents who experience delayed MTX-clearance and renal dysfunction with the enzyme Glucarpidase which rapidly hydrolyses MTX to non-toxic metabolites and lowers the serum concentration to avoid life threatening complications. Glucarpidase should be given if the 24 hour levels of MTX is \> 250 µM, 36 hour levels \> 30 µM or 42 hours levels \> 10 µM together with a reduced kidney function. Glucarpidase treatment should take place within 48 hours from the start of HD-MTX treatment.
2. To evaluate if the early intervention with Glucarpidase reduce the number of days the patients have to stay at the hospital.
3. Evaluate the reduction of health costs of early intervention in patients with delayed MTX-clearance and renal dysfunction.

Arms: arm 1: In the NOPHO ALL-2008 protocol patients with delayed methotrexate elimination (DME) in high-dose methotrexate treatments should be given Glucarpidase (50 ie/kg) with-in 60 hours from start of the methotrexate treatment.
Interventions: intervention 1: Glucarpidase
Intervention descriptions: intervention 1: Patients treated with Glucarpidase if the 24 hour levels of MTX is \>250 µM, 36 hour levels \>30 µM or 42 hours levels \>10 µM together with a reduced kidney function will be compared with patients in just below the tricking values.

Protocol documents:
Clinical trial NCT01312467
Conditions: Adenomatous Polyp Colorectal Cancer Obesity
Sponsor: National Cancer Institute (NCI)
Start date: 2011-03-01; Completion date: 2014-12-01
Enrollment: 45 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to find out whether METFORMIN decreases protein markers in colorectal tissue. This is a phase IIA study of the pharmacodynamics, safety and tolerability of Metformin in decreasing colorectal mucosa in patients with a history of colorectal adenomas in the past 3 years and a BMI \>= 30, with decimals rounded to the nearest whole integer. Metformin as a potential chemopreventive agent for inhibition of the relevant molecular pathways involved in human colorectal carcinogenesis.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine if a 12-week intervention of oral metformin (metformin hydrochloride) treatment among obese patients with a history of colorectal adenomas results in at least a 35% decrease in colorectal mucosa activated pS6serine235 from baseline as assessed via immunostaining.

SECONDARY OBJECTIVES:

I. To assess the effect of metformin on additional relevant biomarkers in serum: metformin levels; fasting insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3; fasting leptin; fasting Adiponectin; fasting and 2 hour post-prandial insulin and glucose.

II. To examine the correlation among biomarkers (serum, tissue). III. To assess the independent effects of treatment on each biomarker, using multivariate regression models to account for clinical and biomarker data.

IV. To document the safety and tolerability of metformin in the study population.

TERTIARY OBJECTIVES:

I. To assess the effect of metformin on additional relevant biomarkers in tissue via immunostaining. This will include the effects on levels of colorectal mucosa proliferation estimated by: phosphorylated AMPK (pAMPK), phosphorylated AKTserine 473 (pAKT), phosphorylated mTOR, phosphorylated insulin receptor (pIR), phosphorylated IGF-1 (pIGF-1) receptor, and Ki-67.

II. To cross-validate immunostaining results with Western blotting experiments in a subset of consecutive patients for the following endpoints: phosphorylated S6serine235 (pS6serine235), phosphorylated AMPK (pAMPK), phosphorylated AKTserine 473 (pAKT), phosphorylated mTOR, phosphorylated insulin receptor (pIR), phosphorylated IGF-1 (pIGF-1) receptor, and Ki-67.

OUTLINE:

Patients receive metformin hydrochloride orally (PO) once daily (QD) during week 1 and then twice daily (BID) during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 4 weeks.

Arms: arm 1: Patients receive metformin hydrochloride PO QD during week 1 and then BID during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: metformin hydrochloride
Intervention descriptions: intervention 1: None

Protocol documents:
Clinical trial NCT01326481
Conditions: Metastatic Breast Cancer
Keywords: TRC105 Breast Cancer CD105 Endoglin TRACON Pharma Roswell Park Cancer Institute Department of Defense
Sponsor: Tracon Pharmaceuticals Inc.
Start date: 2011-06-01; Completion date: 2014-12-01
Enrollment: 19 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to determine the recommended phase 2 dose and overall safety and tolerability of TRC105 when given in combination with capecitabine for the treatment of patients with progressive or recurrent metastatic breast cancer.

Detailed description:
All patients were required to sign a consent form prior to undertaking any study-related procedures. Prospective patients were screened to determine if they qualified for the study within 28 days of enrollment. Patients who qualified received TRC105 i.v. over 1 to 4 hours on Day 1, Day 4, Day 8 and Day 15 of the initial 21-day cycle and Day 1, Day 8 and Day 15 of every subsequent 21-day cycle in combination with 1000 mg/m2 capecitabine BID for 14 days of each 21-day cycle. Those who tolerated TRC105 without any infusion reactions were eligible for reduced infusion durations. After 3 cycles of treatment, patients who demonstrated a response of complete response (CR), partial response (PR) or stable disease (SD) were eligible for additional treatment for up to six months (9 total cycles). Upon discussion with TRACON, patients judged by the Principal Investigator to be benefiting from treatment were able to continue treatment on this protocol beyond six months.

Toxicities were graded according to the NCI CTCAE Version 4.0. Patients who exited the study for reasons other than drug-related toxicity prior to completion of the first 21-day cycle were replaced. Intra-patient dose escalation was not allowed.

Arms: arm 1: All patients received TRC105 + capecitabine
Interventions: intervention 1: TRC105 intervention 2: Capecitabine
Intervention descriptions: intervention 1: IV intervention 2: oral

Protocol documents: