Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Prostatic Neoplasms

Disease Progression

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Lipid Regulating Agents

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Bone Density Conservation Agents

Hormones

Calcium

Atorvastatin

Celecoxib

Calcium, Dietary

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Enzyme Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

atorvastatin calcium

celecoxib

laboratory biomarker analysis

Susan Goodin, PhD, FCCP, BCOP

RATIONALE: Atorvastatin calcium and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atorvastatin calcium together with celecoxib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving atorvastatin calcium together with celecoxib works in treating patients with rising PSA levels after local therapy for prostate cancer.

OBJECTIVES:

Primary

* To determine the effect on the biological activity, as assessed by prostate-specific antigen (PSA) response, of atorvastatin calcium and celecoxib in patients with D0 prostate cancer.

Secondary

* To document the safety and feasibility of atorvastatin calcium and celecoxib in patients with early-stage prostate cancer.
* To evaluate the effects of the combination of atorvastatin calcium and celecoxib on nuclear factor-kB (NFkB), extracellular signal-regulated kinase (ERK), prostaglandin E2 (PGE2), and IL6 in peripheral blood mononuclear cells (PBMC).

OUTLINE: This is a multicenter study.

Patients receive oral atorvastatin calcium once daily and oral celecoxib twice daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood sample collection at baseline and after completion of study therapy for correlative studies.

After completion of study therapy, patients are followed up every 3 months for 2 years.

Atorvastatin Calcium and Celecoxib in Treating Patients With Rising PSA Levels After Local Therapy for Prostate Cancer

Phase II Trial of Atorvastatin and Celecoxib in Patients With Hormone-Dependent Prostate-Specific Antigen Progression After Local Therapy for Prostate Cancer.

PSA response was defined as a decrease in slope of at least 25%, when log (PSA) is plotted vs. time.

Rutgers Cancer Institute of New Jersey

National Cancer Institute (NCI)

Rutgers, The State University of New Jersey

Professor of Medicine, RWJMS

atorvastatin calcium

celecoxib

laboratory biomarker analysis

Atorvastatin and Celecoxib

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Susan Goodin PharmD, FCCP, BCOP

A total of 27 patients were enrolled but only 26 were evaluable as one patient withdrew consent prior to starting therapy.

PSA Response

Overall Study

Nutritional and Metabolic Diseases

Syndrome

Metabolic Syndrome

Insulin Resistance

Hyperinsulinism

Metabolic Diseases

Glucose Metabolism Disorders

Androgens

Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

Patients receive atorvastatin calcium PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

placebo

Jue Wang, MD

This randomized pilot clinical trial studies atorvastatin calcium in preventing metabolic syndrome in patients with prostate cancer receiving long-term androgen-deprivation therapy. Atorvastatin calcium may help prevent or reduce metabolic syndrome caused by long-term androgen-deprivation therapy

PRIMARY OBJECTIVES:

I. To evaluate in a pilot study a preliminary estimate of the overall change of metabolic syndrome score in men undergoing or who have undergone androgen-deprivation therapy for treatment or the control of prostate cancer.

II. To assess the effectiveness of Atorvastatin (atorvastatin calcium) on the prevention of metabolic syndrome in men undergoing or who have undergone androgen-deprivation therapy for treatment or the control of prostate cancer.

SECONDARY OBJECTIVES:

I. To document the safety and tolerability of Atorvastatin in this patient population.

II. To assess the impact of Atorvastatin on mean change in prostate specific antigen (PSA) and PSA velocity.

III. The collection and banking of blood and serum on subjects for future analysis that will be proposed in future institutional review board (IRB) submissions.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive placebo orally once daily for 6 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive atorvastatin calcium orally once daily for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and at 6 months thereafter.

Atorvastatin Calcium in Preventing Metabolic Syndrome in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy

A Pilot Study of Atorvastatin on Prevention of Metabolic Syndrome in Subjects With Prostate Cancer on Long Term Androgen-deprivation Therapy

A total of 60 subjects will yield 80% power at the 0.05 two-sided level of significance to detect 3.40 difference of the mean change in metabolic syndrome scores after 6 months between arms using a Mann-Whitney test.

The overall change of metabolic syndrome score is evaluated in men undergoing or who have undergone androgen-deprivation therapy for treatment or the control of prostate cancer.

Safety will be assessed when approx 30 patients (50%) have completed the 3 month assessment based on the frequency and % of adverse events. 5 patients experiencing any non-hematologic, non-androgen deprivation related grade 3 or greater AE would trigger a systematic review of the AE experience. The frequency of AEs will be compared between the placebo and Atorvastatin groups using a Fisher's Exact test. A p-value of 0.20 will be considered significant for the interim assessment.

The effectiveness of Atorvastatin (atorvastatin calcium) on the prevention of metabolic syndrome is evaluated in men undergoing or who have undergone androgen-deprivation therapy for treatment or the control of prostate cancer.

Optional samples collected for future research that will be proposed in future IRB submissions.

University of Nebraska

Precancerous Conditions

Antineoplastic Agents

Other Dietary Supplements

Sulindac

Inulin

Patients receive oral atorvastatin once daily.

Patients receive oral sulindac twice daily.

Patients receive oral oligofructose-enriched inulin (Raftilose Synergy 1) twice daily.

Patients receive an oral placebo twice daily.

oligofructose-enriched inulin

sulindac

Paul Limburg

This randomized phase II trial is studying atorvastatin calcium to see how well it works compared to oligofructose-enriched inulin, sulindac, or a placebo in preventing cancer in patients at increased risk of developing colorectal neoplasia. Chemoprevention is the use of certain drugs or substances to keep cancer from forming, growing, or coming back. The use of atorvastatin calcium, oligofructose-enriched inulin, or sulindac may stop cancer from forming in patients at increased risk of colorectal neoplasia. It is not yet known whether atorvastatin calcium, oligofructose-enriched inulin, or sulindac are more effective than a placebo in preventing cancer in patients at increased risk of developing colorectal neoplasia.

PRIMARY OBJECTIVE:

I. Percent change in number of rectal aberrant cryptic foci (ACF) as measured by magnification chromoendoscopy

SECONDARY OBJECTIVES:

I. Screening for possible phase III testing II. Effects on proliferation (Ki67 expression) and apoptosis (caspase-3 expression) as measured by biopsy samples obtained from normal-appearing rectal mucosa at baseline and after completion of study treatment III. Correlation of endoscopic features with histologic characteristics of rectal ACF IV. Observation of the natural history of rectal ACF in patients receiving placebo V. Adverse events VI. Utilization of a biospecimen repository archive

OUTLINE: This is a multicenter, prospective, randomized, partially blinded, placebo-controlled study. Patients are stratified according to history of prior surgical resection of the colon (yes vs no) and number of rectal aberrant cryptic foci (ACF) (5-9 vs \>= 10). Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive oral atorvastatin calcium once daily.

ARM II: Patients receive oral sulindac twice daily.

ARM III (blinded arm): Patients receive oral oligofructose-enriched inulin (Raftilose Synergy 1) twice daily.

ARM IV (blinded arm): Patients receive an oral placebo twice daily.

In all arms, treatment continues for 6 months in the absence of unacceptable toxicity.

Tissue samples are collected at baseline and at the completion of study treatment. Tissue is examined by immunohistochemistry for proliferation (Ki67) and apoptosis (cleaved caspase-3).

After completion of study treatment, patients are followed at approximately 30 days.

Atorvastatin Calcium, Oligofructose-Enriched Inulin, or Sulindac in Preventing Cancer in Patients at Increased Risk of Developing Colorectal Neoplasia

Randomized, Phase II Trial of Atorvastatin, RAFTILOSE Synergy 1, and Sulindac Among Patients at Increased Risk for Sporadic Colorectal Neoplasia

At the Pre-Intervention Evaluation, rectal ACF will be classified with respect to ACF number, crypt number, crypt size, tissue plane, staining intensity, and (optional) lumen shape for each subject. At the Post- Intervention Evaluation, these same parameters will be recorded and incident vs prevalent rectal ACF status will also be recorded. Compare each non-placebo arms versus the placebo arm to screen the three active study agents for possible phase III testing.

Tissue is examined by immunohistochemistry for Ki67. Measured by biopsy samples obtained from normal-appearing rectal mucosa at baseline and after completion of study treatment. Wilcoxon will be used to assess significant differences between the intervention arms.

Tissue is examined by immunohistochemistry for cleaved caspase-3. Measured by biopsy samples obtained from normal-appearing rectal mucosa at baseline and after completion of study treatment. Wilcoxon will be used to assess significant differences between the intervention arms.

Defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with participation in a study, whether or not related to that participation. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 3.0. Number of adverse events per grade level.

Common Toxicity Criteria for Adverse Events (CTCAE) v3

Patients receive 20 mg tablet oral atorvastatin once daily.

Arm I (Atorvastatin Calcium)

Patients receive 150 mg tablet oral sulindac twice daily.

Arm II (Sulindac)

Patients receive 6gm powder oral oligofructose-enriched inulin (Raftilose Synergy 1) twice daily.

Arm III (Oligofructose-enriched Inulin)

Patients receive an oral placebo (maltodextrin powder) twice daily.

Arm IV (Placebo)

Total

Age, Continuous

Gender

History of prior surgical resection of the colon: Yes vs. No

History of Surgical Resection

Variation in endpoint measurement across sites, relatively small sample size, and rectal biomarker assessments only may have contributed to challenges in full data interpretation.

Dr. Paul Limburg

The study was designed to test the hypotheses of observing a 25% difference in % change ACF over baseline, between patients treated with atorvastatin compared to placebo. N=25 subjects per group yielded 93% power to detect this difference using a 2 sided t-test at significance level of 0.05. Non-parametric tests (eg, Wilcoxon Rank Sum) could be used if the statistical assumptions of the t-test were violated.

The study was designed to test the hypotheses of observing a 25% difference in % change ACF over baseline, between patients treated with sulindac compared to placebo. N=25 subjects per group yielded 93% power to detect this difference using a 2 sided t-test at significance level of 0.05. Non-parametric tests (eg, Wilcoxon Rank Sum) could be used if the statistical assumptions of the t-test were violated.

The study was designed to test the hypotheses of observing a 25% difference in % change ACF over baseline, between patients treated with oligofructose-enriched inulin compared to placebo. N=25 subjects per group yielded 93% power to detect this difference using a 2 sided t-test at significance level of 0.05. Non-parametric tests (eg, Wilcoxon Rank Sum) could be used if the statistical assumptions of the t-test were violated.

Signed Rank p-value for comparison of % change in ACF within each randomization arm.

The population used for the analysis is patients having at least 5 rectal ACF and completing both the pre- and post-intervention MCE assessments and using intention to treat principles.

Percent Change in Number of Rectal Aberrant Cryptic Foci (ACF) as Measured by Magnification Chromoendoscopy

Wilcoxon Rank Sum p-value for comparison of % change in Ki67 between atorvastatin and placebo.

Wilcoxon Rank Sum p-value for comparison of % change in Ki67 between sulindac and placebo.

Wilcoxon Rank Sum p-value for comparison of % change in Ki67 between oligofructose-enriched inulin and placebo.

Patients with assay data from baseline and post-intervention biopsy samples of normal-appearing rectal mucosa.

Effects on Proliferation (Ki67 Expression).

Wilcoxon Rank Sum p-value for comparison of % change in apoptosis between atorvastatin calcium and placebo.

Wilcoxon Rank Sum p-value for comparison of % change in apoptosis between sulindac and placebo.

Wilcoxon Rank Sum p-value for comparison of % change in apoptosis between oligofructose-enriched inulin and placebo.

Effects on Apoptosis (Caspase-3 Expression).

Grade 1

Grade 2

Grade 3

Adverse Events.

Immune System Diseases

Rare Diseases

Graft vs Host Disease

Homologous Wasting Disease

Acute Graft Versus Host Disease

Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection.

Undergo myeloablative allogeneic PBSC transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Atorvastatin Calcium

Peripheral Blood Stem Cell Transplantation

Marco Mielcarek

This phase II trial studies donor atorvastatin treatment for the prevention of severe acute graft-versus-host disease (GVHD) in patients undergoing myeloablative peripheral blood stem cell (PBSC) transplantation. Giving chemotherapy and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also prevent the patient's immune system reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving atorvastatin to the donor before transplant may prevent this from happening.

PRIMARY OBJECTIVES:

I. To assess whether 2 weeks of donor statin treatment reduces the risk of severe acute GVHD.

SECONDARY OBJECTIVES:

I. To assess whether 2 weeks of statin treatment of normal PBSC donors is feasible, tolerable and safe.

OUTLINE:

Donors receive atorvastatin orally (PO) beginning on day -14 and continuing until the last day of stem cell collection.

Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation

Donor Statin Treatment for Prevention of Severe Acute GVHD After Myeloablative Hematopoietic Cell Transplantation

Cumulative incidence rate of grade 3-4 acute GVHD with death as a completing risk, assessed at day 100 in the patients/recipients.

Cumulative incidence rate of chronic extensive GVHD with death as a competing risk, assessed at 2 years in the patients/recipients.

Evaluated as Kaplan-Meier estimate in the patients/recipients.

Cumulative incidence rate of grades II-IV acute GVHD with death as a competing risk, assessed at 100 days in the patients/recipients.

Cumulative incidence rate of non-relapse mortalities, assessed at day 100 in the patients/recipients.

Cumulative incidence rate of non-relapse mortalities, assessed at one year in the patients/recipients.

Determined and presented as Kaplan-Meier estimates, assessed at 1 year in the patients/recipients.

Cumulative incidence rate of recurrent or progressive malignancy with death as a competing risk, assessed at 3 years in the patients/recipients.

National Heart, Lung, and Blood Institute (NHLBI)

Fred Hutchinson Cancer Center

Principal Investigator

Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.

Patient Adverse Events

Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier.

Donor Adverse Events

Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo myeloablative allogeneic PBSC transplant

Atorvastatin Calcium: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo myeloablative allogeneic PBSC transplant

Donors

Patients

Dr. Marco Mielcarek

Grade 3-4 Acute GVHD

Chronic Extensive GVHD

Disease-free Survival

Grades II-IV Acute GVHD

Non-relapse Mortality

Overall Survival

Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity

Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy

Recurrent or Progressive Malignancy

Skin and Connective Tissue Diseases

Breast Neoplasms

Carcinoma

Hyperplasia

Carcinoma in Situ

Carcinoma, Lobular

Breast Carcinoma In Situ

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Carcinoma, Ductal

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Adenocarcinoma

Participants receive oral atorvastatin once daily for 3 months.

Participants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months.

Participants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months.

Participants do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies.

Banu Arun

Chemoprevention is the use of certain drugs to keep cancer from forming. The use of atorvastatin (Lipitor) may prevent breast cancer. This randomized phase I trial is studying the best dose of atorvastatin in preventing breast cancer in women at increased risk for breast cancer.

PRIMARY OBJECTIVES:

I. To determine the minimum biological effective dose (MBED) of atorvastatin required to induce modulation in the proliferation marker, Ki-67, in breast tissue of women who are at high risk to develop breast cancer. We will evaluate pre- and post atorvastatin treatment (4 dose levels) expression of Ki-67 in samples obtained via FNA from breast tissue of women at high risk for breast cancer. This specific aim tests the hypothesis that treatment with atorvastatin will induce a decrease in Ki-67.

SECONDARY OBJECTIVES:

I. To evaluate atorvastatin induced modulation of breast cancer biomarkers markers (EGFR, P-EGFR, ER, p21, p27, bcl-2, CC3, cytology) and drug related markers (LXR, total cholesterol, LDL, HDL, CRP) in women who are at high risk to develop breast cancer.

II. To determine plasma and tissue levels of atorvastatin and two of its hydroxylated metabolites (ohydroxyatorvastatin and p-hydroxyatorvastatin) in women who are treated with atorvastatin and to correlate these levels with Ki-67 levels. III. To correlate changes in Ki-67 and the above-described panel of biomarkers with HMG-CoA reductase genotype.

OUTLINE: Participants are randomized to 1 of 4 arms.

ARM I: Participants receive oral atorvastatin once daily for 3 months.

ARM II: Participants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months.

ARM III: Participants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months.

ARM IV: Participants do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Atorvastatin Calcium and Celecoxib in Treating Patients With Rising PSA Levels After Local Therapy for Prostate Cancer	NCT01220973	Prostate Cancer	atorvastatin ca... celecoxib laboratory biom...	18 Years - 120 Years	Rutgers, The State University of New Jersey
Atorvastatin Calcium in Preventing Metabolic Syndrome in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy	NCT01555632	Recurrent Prost... Stage I Prostat... Stage IIA Prost... Stage IIB Prost... Stage III Prost... Stage IV Prosta...	atorvastatin ca... placebo	19 Years -	University of Nebraska
Atorvastatin Calcium, Oligofructose-Enriched Inulin, or Sulindac in Preventing Cancer in Patients at Increased Risk of Developing Colorectal Neoplasia	NCT00335504	Colon Cancer Precancerous Co... Rectal Cancer	oligofructose-e... sulindac placebo atorvastatin ca... laboratory biom...	40 Years -	National Cancer Institute (NCI)
Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation	NCT01525407	Malignant Neopl...	Allogeneic Hema... Atorvastatin Ca... Peripheral Bloo...	18 Years -	Fred Hutchinson Cancer Center
A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer	NCT00637481	Atypical Ductal... Breast Cancer Ductal Breast C... Lobular Breast ...	atorvastatin ca... laboratory biom...	18 Years - 72 Years	National Cancer Institute (NCI)
A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer	NCT00637481	Atypical Ductal... Breast Cancer Ductal Breast C... Lobular Breast ...	atorvastatin ca... laboratory biom...	18 Years - 72 Years	National Cancer Institute (NCI)
Atorvastatin Calcium and Celecoxib in Treating Patients With Rising PSA Levels After Local Therapy for Prostate Cancer	NCT01220973	Prostate Cancer	atorvastatin ca... celecoxib laboratory biom...	18 Years - 120 Years	Rutgers, The State University of New Jersey
A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer	NCT00637481	Atypical Ductal... Breast Cancer Ductal Breast C... Lobular Breast ...	atorvastatin ca... laboratory biom...	18 Years - 72 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for atorvastatin calcium