Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Angiogenesis Inhibitors

Sunitinib

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Sunitinib, SUTENT, 50 mg daily p.o., on schedule 4/2, for 2 cycles. Two weeks of rest prior to surgery (week 11 and 12).

Radical nephrectomy at the end of week 12. Sunitinib 50 mg/d, schedule 4/2, reintroduced 2 weeks after surgery (week 14, may be postponed by one or two weeks if wound healing delay or surgical complications). Treatment until disease progression, unacceptable toxicity or consent withdrawal. Dose reduction depending on the type and severity of toxicity.

At the end of the treatment period patients will be treated at the discretion of the Investigator.

Sunitinib (SUTENT)

Stephane OUDARD, MD

The aim of this study is to identify and/or validate biomarkers and imaging markers to predict and monitor the activity of a new class of therapeutic agents called antiangiogenics for the treatment of metastatic renal cell carcinoma (mRCC). Suntinib, approved for this indication, will be administred before and after nephrectomy and biomarkers sampling and imaging will be operated to monitor the activity and identify prognostic factors in mRCC.

BACKGROUND Sunitinib, SUTENT, is a promising multi-target TKI in the treatment of metastatic renal cell carcinoma after cytokine failure. In previous phase II studies, ORR is 40% and TTP = 8,7 months. A phase III randomized trial of Sunitinib versus interferon alpha as first-line therapy for patients with mRCC showed a significantly longer PFS in the Sunitinib group (11 months) than in the interferon group (5 months), hazard ratio of 0.42 (95% CI, 0.32 to 0.54, p \< 0.001). Initial approval in second line treatment of mRCC was extended to first line therapy on 11-01-2007.

Mechanisms of action involved in the therapeutic effects of antiangiogenic compounds are not fully elucidated. As of today, there are no validated biomarkers or imaging markers to predict and monitor the activity of this type of compound.

Recent findings in the field of cancer biology, tumor angiogenesis, immunology and imaging provide several biomarker candidates that can be assessed in metastatic renal cell carcinoma.

BASIC RESEARCH Biomarkers It seems interesting to measure the different biological markers that could be modulated by this antiangiogenic therapeutic. Some of them are known as prognostic factors in the metastatic renal carcinoma, others are directly linked to the mechanism of action of Sunitinib. Due to the biopsy prior to treatment initiation and nephrectomy after treatment initiation, it will be possible to evaluate biomarkers modification and to assess the potential link with the tumour response.

VHL gene alterations (mutations, deletions, and hypermethylations) are observed at high frequencies of up to 80% in cases of clear-cell renal cell carcinoma. The molecular mechanisms involved in angiogenesis in the presence of such genetic alterations are not yet well known. The functions of the pVHL/aHIF/VEGF/angiogenesis pathway will be investigated in all the renal cell carcinoma obtained from the biopsy and nephrectomy. Molecular markers defined by VHL status, expression and proteomic profiling may be helpful in predicting the responders.

Sunitinib is a potent inhibitor of the tyrosine kinase activity of several receptors: VEGFR-2, the main receptor responsible for mediating the proangiogenic effects of vascular endothelial growth factor (VEGF), expressed by vascular endothelial cells; PDGFR, the receptor for the platelet-derived growth factor (PDGF), expressed in pericytes which serve as structural supporting cells for endothelial cells. Consistent with its biochemical activity, Sunitinib inhibits the in vitro mitogenic response of human umbilical vein endothelial cells (HUVECs) stimulated by VEGF or bFGF (basic fibrosblast growth factor), another proangiogenic factor.

VEGF gene polymorphisms In physiologic and pathologic conditions, important variations in VEGF blood levels have been reported to correlate with constitutional VEGF-A gene polymorphisms located in intronic regions. Moreover, VEGF-A polymorphisms have been described as predisposition and prognostic factors in several human malignancies such as bladder, breast, melanoma, prostate and head and neck carcinomas. Hence, it is interesting to see whether these polymorphisms could affect tumor and clinical presentation and correlate with VEGF-levels and response to antiangiogenic treatment with sunitinib.

Immunology Tumor angiogenesis can impact immune response in renal cell carcinoma patients. A naturally occurring CD4+ T cell subset, regulatory CD4+CD25+ T cells, has emerged as the dominant T cell population governing peripheral self- tolerance by inhibiting effector T cell. The ability of anti-angiogenic therapy to block VEGF may allow better maturation of dendritic cells and a reduction of the number of regulatory CD4+CD25+T cells.

The aim of this project will be to test whether the administration of Sunitinib modulates the concentrations of regulatory CD4+CD25+T cells, and if a correlation between the immunology parameters and the response can be observed.

Imaging Radiological evaluation of tumor response is also challenging with anti-angiogenic drugs. Criteria based solely on size may be inadequate for evaluation of anti-angiogenic therapy efficacy. The unbridled expansion of tumor vessels leads to development of abnormal vessels, with distinct microvascular characteristics: high perfusion (blood flow), and porous walls leaking molecules into the interstitium (permeability).

New imaging techniques as dynamic contrast-enhanced CT are being developed to quantify and characterize these unique properties, and may be used as markers of response to angiogenesis inhibitors. Imaging assays of angiogenic status therefore offer the potential to clinically measure anti angiogenic effects of drugs on the tumor vessels themselves, effects that may not be reflected in changing tumor dimensions. These effects may be detectable hours or days from time of treatment initiation, rather than in weeks or months needed typically to detect a change in tumor size. Exploration of local tumor vascular architecture can help to understand mechanism of action of Sunitinib. This vasculature seems to be of poor functionality and tumor vascularization cannot be adequately assessed only by global index such as global tumor blood flow. In addition, exploration of renal tumor vascularization with contrast-enhanced US will be performed to compare blood flow determined by CT and US.

Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma

A Study of Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma With Sunitinib BEFORE and AFTER Nephrectomy

Pfizer

National Cancer Institute, France

Assistance Publique - Hôpitaux de Paris

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Usual care and exposure to a visually enriched milieu (landscape photograph)

Usual care, exposure to a visually enriched milieu and audio taped guided visualization with healing suggestions.

Visualization relaxation

Visual Milieu Enhancement (Fine art photograph)

Susan L Troyan, MD

This is a study to assess whether healing suggestions and enhancing visual milieu (large fine art photographs) will improve mental and physical measures of well-being and recovery from surgery. The study will compare breast cancer patients undergoing identical skin sparing mastectomy and reconstruction surgery randomized to three groups:

1. Usual care control group
2. Usual care and exposure to fine art photograph
3. Usual care and fine art photograph and guided visualization tapes.

In the course of surgical procedures and hospitalization, patients are stressed not only by the discomforts and anxieties associated with their illness and treatment but also by the sterile, intimidating medical environment, with no access to the natural environment. Clinical studies from environmental medicine have suggested that during hospital confinement patients benefit from visually pleasing décor. Enhancing the medical milieu can alleviate patient anxiety and discomfort as well as improve markers of stress such as blood pressure and requirement for analgesics. In addition, research has shown the effectiveness of stress reduction approaches such as Relaxation Response, Guided Imagery, and Hypnosis in mediating clinical psychophysiology overall. Such studies have also shown the lowering of stress levels, inducing faster recovery from surgical anesthesia and perhaps even speeding physical healing overall. Use of these techniques has been shown to give people a greater sense of self-control as well and reduce stress reactions that affect health.

The proposed study represents the next step testing clinical efficacy of a behavioral medicine intervention with breast cancer patients undergoing mastectomy and reconstruction surgery. The current study extends prior research on accelerating healing outcomes through the use of non-pharmacological mental interventions. One prior study demonstrated accelerated bone fracture healing using hypnosis in otherwise healthy young adults. A second study showed enhanced post-surgical wound healing in healthy women undergoing reduction mammoplasty. The current study will generate new data about enhancing outcomes for breast cancer patients undergoing mastectomy and reconstruction. The goal of the trial is to determine whether these ancillary treatments enhance psychological and physical post-surgical recovery as compared to usual care only. The study provides an upside potential to enhance patient well being and to accelerate post-surgical recovery with minimal risk. Should significant positive findings result from this study, it will constitute a pilot test of such modifications of the healthcare delivery environment with an eye toward stimulating greater patient well being and shorter length of stay.

Study of Fine Art Photographs and Visualization Tapes to Improve Surgical Recovery in Breast Cancer

Using Visual Milieu Enrichment and Guided Visualization to Augment Patient Well-being and Post-surgical Recovery

Beth Israel Deaconess Medical Center

Professor of Psychology in the Department of Psychiatry

Blood and Lymph Conditions

Hematologic Neoplasms

Hematologic Diseases

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Chrysarobin

Immunoglobulins, Intravenous

Ibrutinib

gamma-Globulins

Rho(D) Immune Globulin

Idelalisib

Bilirubin

Interventions to be administrated are :

* Clinical examinations
* Biological statement
* Blood samples for pharmacokinetics exploration
* Imagery with positron emission tomography scan or resonance magnetic imagery
* Saliva samples for genetics analyses
* Blood samples for treatment mutation resistance search
* Quality of life scale questionary
* Detection of adverse events

Blood samples for pharmacokinetics exploration

Efficacity will be assessed with 3 sessions of resonance magnetic imaging or positron emission tomography scan

Imagery

Quality of life will be evaluated with questionaries 5 times during the study

Quality of life scale

The detection will be assessed using the AMA (assistance des malades ambulatoires) system

Detection of adverse events

Saliva samples will be collected to explore genetic characteristics of germinal DNA (genes involved in drug pharmacokinetic)

Saliva samples

A unique blood sample will be performed in order to determine characteristics of tumoral DNA (resistance to treatment mutation)

Blood sample

The following parameters will be assessed :

* Complete blood count
* Hemoglobin
* Hepatic enzymes
* Creatinine clearance
* Lactate dehydrogenase rate
* Total bilirubin rate
* Cluster of differentiation 4 T lymphocytes rate
* Total gamma-globulins rate

Biological statement

The clinical examination are composed by :

* Weigh, Height and body mass index measurement
* Clinical state of patient during examination
* Stage of the disease (OMS grade, binet classification, Ahn Arbor classification)
* Presence of B symptomatology
* Prognostic factors (Genetic, Mantle Cell Lymphoma International Prognostic Index, Follicular Lymphoma International Prognostic Index, presence of lymph nodes, other target organs ...)

Clinical examination

Loïc Ysebaert, MD

Recently, European Medicines Agency approved ibrutinib and idelalisib to treat Chronic Lymphocytic Leukemia (CLL) and two lymphomas: Follicular Lymphoma (FL) for ibrutinib and Mantle cell lymphoma (MCL) for idelalisib.

Clinical trials for ibrutinib and idelalisib were performed with a small number of patients (300-350) and showed several side effects profiles. Since, pharmacokinetic properties of these 2 drugs highlight a interindividual variability of pharmacokinetic. The aim of this study is to determine the association between clinically significant side effects occurrence during the first year of treatment and plasma mean concentration of the steady state of ibrutinib or idelalisib at 1 month.

Recently, European medicines agency approved ibrutinib and idelalisib in the treatment of Chronic Lymphocytic Leukemia (CLL) and two lymphomas: Follicular Lymphoma (FL) for ibrutinib and Mantle cell lymphoma (MCL) for idelalisib. Nevertheless, clinical trials for these two drugs were performed for only 300-350 patients and showed several side effects profiles, the most frequent were diarrhea, infection, cutaneous rash... For some patients, treatment had to be reduced or stopped temporary or definitely.

Pharmacokinetic properties of these two drugs highlight an interindividual pharmacokinetic considerable variability. The aim of this clinical research study is to determine the association between clinically significant side effects occurrence during the first year of treatment (serious adverse reaction and/or grade CTCAE ≥ 3 and/or leading a dosage concession) and plasma mean concentration of the steady state of ibrutinib or idelalisib performed at 1 month.

To determine plasma mean concentration of the steady state of ibrutinib or idelalisib, blood tests will be performed every scheduled monitoring at visit 1 month during a pharmacokinetic exploration and during scheduled medical consultation (2, 3, 6 and 12 months) and every unscheduled visit in case of side effect occurrence.

Every scheduled monitoring visit, blood tests will be performed to determine plasma concentration in drug. Complementary blood or salivary samples will be collected before the treatment, 24 months later and in case of relapse to determine genetic characteristics. In parallel, a logbook will be completed by the patient to collect side effects. Finally, an oncology certified nurse call patients every 2 weeks. In case of side effect occurrence a visit will be organized in the next 3 days and a blood test will be performed.

Samples to be collected are :

* Blood samples for dosage of drug in plasma (No DNA)
* Blood samples (genetic profile of drug elimination and presence of treatment resistance mutation) and saliva samples (genetic profile drug elimination )

Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib

Real Life Assessment of the Association and Its Determinants Between Side Effects and Plasmatic Concentrations of Two Protein Kinase Inhibitors: Ibrutinib (IMBRUVICA®) and Idelalisib (ZYDELIG®) in Hematological Malignancies Treatment.

Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit

complete response, partial, stable disease, disease progression

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma	NCT00930345	Metastatic Rena...	Sunitinib (SUTE...	18 Years -	Assistance Publique - Hôpitaux de Paris
Study of Fine Art Photographs and Visualization Tapes to Improve Surgical Recovery in Breast Cancer	NCT00179634	Breast Neoplasm...	Visualization r... Visual Milieu E...	18 Years -	Beth Israel Deaconess Medical Center
Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib	NCT02824159	Hematological M...	Blood samples f... Imagery Quality of life... Detection of ad... Saliva samples Blood sample Biological stat... Clinical examin...	18 Years -	University Hospital, Toulouse

Spots Global Cancer Trial Database for imagery

Every month we try and update this database with for imagery cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for imagery

Every month we try and update this database with for imagery cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for imagery cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.