Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Inflammation

Fibrosis

Radiation Injuries

Radiation Fibrosis Syndrome

Pneumonia

Radiation Pneumonitis

Syndrome

Lung Diseases

Lung Diseases, Interstitial

Respiratory Tract Diseases

Lung Injury

Camurati-Engelmann Disease

Anti-Arrhythmia Agents

Antihypertensive Agents

All Drugs and Chemicals

Vasoconstrictor Agents

Micronutrients

Antineoplastic Agents

Vitamins

Losartan

Angiotensin Receptor Antagonists

Mitogens

Angiotensin II

Giapreza

Angiotensinogen

Angiotensin-Converting Enzyme Inhibitors

Vitamin A

Retinol palmitate

Angiotensin II Type 1 Receptor Blockers

Retinol

Participants who underwent breast conservation surgery will take losartan in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Participants who underwent breast conservation surgery will take placebo in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Participants who underwent a mastectomy will take losartan in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Participants who underwent a mastectomy will take placebo in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Losartan 25 milligram capsule

Placebo

Katie Hess, Bachelors

Paige Bordelon, MPH

Patricia H Hardenbergh, MD

This study will evaluate the efficacy of Losartan (LOS), an FDA-approved transforming growth factor beta-1 (TGF-β1) blocker, to decrease radiation induced fibrosis (RIF) in the breast and the lung of breast cancer patients, testing the hypothesis that Losartan will decrease RIF, TGF- β1 and cellular senescence/inflammation in the breast and the lung of irradiated breast cancer patients relative to placebo treatment and consequently improve clinical outcomes in breast cancer patients.

This single site study will be conducted at the Shaw Cancer Center in Edwards, Colorado. A block, double-blinded, placebo-controlled, randomized phase II design will be utilized .

Study participants will be blocked by surgical intervention (breast conserving surgery vs. mastectomy) and then randomized, 1:1, into the treatment and control arms for a total of four study arms. The research team and study participants will be blinded to the study arm and a placebo will be used to reduce detection bias in the reporting of outcomes. Selection bias will be minimized through the randomization of study arms.

Study participants will be prescribed 25mg capsules of placebo or the investigational drug, Losartan, to be taken by mouth once daily. The treatment start date will be the day that subject begins radiation therapy. Radiation therapy will continue to be prescribed in accordance with local clinic procedures. Treatment with the study intervention will continue for one year upon completion of radiation therapy. All participants will be assessed for fibrosis, cosmetic outcomes, and incidence of reoperation for 18 months following the completion of radiation therapy.

Participants will be blocked by surgical type (breast conservation surgery/mastectomy) and then randomized 1:1 in a parallel design into treatment and control arms. All participants will take an oral 25 milligram tablet once daily of either losartan or placebo.

Assessments of fibrosis will include provider assessments and participant reported outcomes of fibrosis and cosmesis, the participant's decision for reoperation, laboratory assessments of inflammatory biomarkers, a CT scan and bilateral mammograms.

Participants, research staff and clinicians will be blinded from study group assignment.

Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

A Pilot Study of Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

There is no plan to share individual participant data (IPD) with other researchers.

Fibrosis will be assessed by a radiation oncology provider using the Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) scale. 0=Fibrosis absent, not detectable. 1=Fibrosis is Barely Palpable; 2=Definite increased density; 3=Very marked density, retraction and firmness and fixation

Radiographic lung fibrosis will be assessed with high resolution CT scans of the thorax. Thorax CT scans will be fused to the radiation planning CT scan for confirmation of the overlap of fibrosis with the radiation field.

Cellular senescence, and senescence-associated secretory phenotype (SASP) including TGF-β and inflammation will be quantified in the treatment and control group. A novel and expert approach to measure senescent cells in serum will be utilized.

Bilateral mammographic determination of breast volume will be calculated at routine follow-up intervals. Breast shrinkage associated with radiation-induced fibrosis will be assessed by monitoring the change in the breast volume of the treated breast from baseline to 18 months following completion of radiation therapy. Measurement of breast volume on both breasts will use breast height in centimeters (cm) (H), breast width in cm (W) and compression thickness in cm (C), from a craniocaudal projection. Volume in milliliters (mL) = (π/4) x H x W x C. Mammograms will also provide a distance measurement, in centimeters, on the nipple line from nipple to pectoralis muscle and a length measurement, in centimeters, from the superior to inferior margin that bisects the Posterior to Nipple Line (PNL) at a 90° angle.

Cosmesis will be assessed using a clinician assessment The Harvard Cosmesis Scale: 1=Excellent (Treated breast nearly identical to untreated breast); 2=Good (Treated breast slightly different from untreated breast); 3=Fair (Treated breast clearly different from untreated breast but not distorted); 4=Poor Treated breast seriously distorted.

Self-reported participant quality of life will be assessed by Breast-Q Reconstruction Module. The Breast-Q, Version 2.0 tool was developed to assess participant's perception of clinical outcomes in both psychological and satisfaction domains will be used.

* Psychosocial Well-Being module: measures psychological well being
* Physical Well-Being
* Chest module: measures pain or tightness and difficulty with mobility
* Satisfaction with Breasts (Post-Op) module: satisfaction with breast size, how bras fit, and appearance in mirror clothed or unclothed, as well as how breasts feel when they are touched.
* Adverse Effects of Radiation module: measures physical changes such as soreness of skin.

The participant's decision to have corrective surgery on either breast after radiation will be recorded at each time-point. Post-mastectomy patients will be considered to have been reoperated if corrective surgery occurred after permanent implant placement.

Steadman Philippon Research Institute

Shaw Cancer Center

Medical Director

Digestive System Diseases

Anastomotic Leak

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Closure of the pelvic peritoneum after anastomosis for middle-low rectal caner.

Closure of the pelvic peritoneum

Nonclosure of the pelvic peritoneum after anastomosis for middle-low rectal caner.

Nonclosure of the pelvic peritoneum

Tang Bo, MD

Li Chuan

Tang Bo, M.D/Ph.D

A randomized controlled clinical trial to compare the short and long outcomes of low anterior resection for middle-low rectal cancer with or without pelvic peritonization.

The Role of Pelvic Peritonization in Laparoscopic or Robotic Low Anterior Resection

Evaluation of Pelvic Peritonization in Robotic or Laparoscopic Low Anterior Resection for Rectal Cancer

The rate of grade III-IV complication according to Clavien-Dindo classification after low anterior resection

C-reactive protein(1, 3, 5, 7 days after operation, and 1 day before discharge, all blood drawn is venous blood)

Clinical diagnostic criteria for anastomotic leakage: 1. Abdominal and systemic infection symptoms: abdominal pain, bloating, fever, elevated white blood cells, PCT, CRP and other inflammation indicators; 2. Gas, pus, feces passing through the pelvic drainage tube, abdominal incision, etc.

Comparison of hospital stay between the two groups

Overall complication rate include I-IV grade

Blood loss will be measured according to the suction and the weight of wet gauze, and then minus the irrigation

Incidence of intestinal obstruction caused by various reasons after surgery

Rate of hospital readmissions due to complications after discharge

Low Anterior resection syndrome caused by rectal surgery

Procalcitonin(1, 3, 5, 7 days after operation, and 1 day before discharge, all blood drawn is venous blood)

Check Neutrophils(1, 3, 5, 7 days after operation, and 1 day before discharge, all blood drawn is venous blood)

interleukin-6(1, 3, 5, 7 days after operation, and 1 day before discharge, all blood drawn is venous blood)

Comparison of cost between the two groups

Southwest Hospital, China

Principal Investigator

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antirheumatic Agents

Cyclophosphamide

Vaccines

Nivolumab

Ipilimumab

All patients receive depletion of regulatory T cells, reoperation, followed by a personalized cancer vaccine and double checkpoint blockade.

depletion of regulatory T cells

resection of relapsed tumor in order to improve clinical condition of the patient and to acquire tumor tissue for vaccine generation

reoperation

4 weekly intradermal injections of lysate-loaded dendritic cells, followed by 3 monthly boost vaccines with tumor lysate and further boost vaccines every three months

cancer vaccine

Immediately one week after the DC-induction vaccines, patients will receive four applications of Nivolumab/Ipilimumab double checkpoint blockade in threeweekly intervals, followed by Nivolumab monotherapy every month for a total duration of one year.

checkpoint blockade

Matthias Eyrich, MD

Paul G Schlegel, MD

Kramm Christof, MD

This phase I/II trials evaluates the feasibility, safety and efficacy of an individualized cancer vaccine, based on autologous, tumor-lysate loaded dendritic cells in children and adolescents with relapsed high-grade gliomas. In addition, regulatory T cells are depleted by a short cycle of metronomic cyclophosphamide upfront of the vaccine in order to facilitate induction of immune responses.

Therapeutic DC vaccines are followed by four cycles of Nivo/Ipi double checkpoint blockade and a Nivolumab monotherapy maintenance in order to optimize the induced T-cell response.

Relapsed high-grade gliomas (in the following addressed as high-grade gliomas = HGG) in children and adolescents represent a very bad prognosis group for which a recommended standard salvage therapy is currently not available.

Combination of Dendritic Cell (DC) vaccination, metronomic cyclophosphamide, and checkpoint blockade will be investigated in the present trial as a new treatment strategy for these patients: metronomic cyclophosphamide has been shown to significantly reduce numbers of regulatory T cells (Treg) without inducing general leukopenia. DCs might induce tumour-directed immune responses thereby facilitating long-term remissions. Efficacy of primed T-cell responses by the vaccine will potentially be enhanced by the application of checkpoint inhibitors Nivolumab (antiPD-L1) and Ipilimumab (antiCTLA4) in the post-vaccine phase and during maintenance.

Cyclophosphamide is an established drug used as an anti-cancer or immunosuppressive substance since decades, with extensive experience when used in low, non-myeloablative dosages. DCs represent an innovative new strategy in cellular immunotherapy. DCs in cancer patients have been used in a number of smaller studies, and in some of these trials, promising results could be obtained. Several studies showed a trend towards a prolonged overall survival with a few long-term survivors which is otherwise extremely rare in this high-risk population. Results seemed to be more favourable in pediatric than in adult patients. Checkpoint inhibitors (antiPD-L1 and/or antiCTLA4) have been shown to exhibit synergistic effects with vaccines in preclinical models, and prelimnary data of several early stage trials have shown promising results. Therefore, our study aims to improve the efficacy of a DC-based therapeutic vaccine by optimizing the conditions upfront of the vaccine (Treg depletion) and improving T-cell responses by checkpoint blockade after the vaccine in the effector phase.

In conclusion, this study will exploit the optimal efficacy of a therapeutic vaccine in children and adolescents with relapsed HGG.

Autologous Dendritic Cells, Metronomic Cyclophosphamide and Checkpoint Blockade in Children With Relapsed HGG

Autologous Dendritic Cells and Metronomic Cyclophosphamide in Combination With Checkpoint Blockade for Relapsed High-Grade Gliomas in Children and Adolescents

overall survival 6 months after diagnosis of relapse

frequency of adverse events associated with metronomic cyclophosphamide

frequency of adverse events associated with the vaccine

frequency of AEs/SAEs associated with Nivolumab and/or Ipilimumab

frequency of CD4+CD25+CD127- regulatory T cells under metronomic cyclophosphamide in % of CD3+

absolute numbers of CD4+CD25+CD127- regulatory T cells under metronomic cyclophosphamide per µl blood

Interferon-gamma Cytotoxic T cell (CTL) assay

correlation of outcome/immune response with histopathology etc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients	NCT05637216	Radiation Induc...	Losartan 25 mil... Placebo	18 Years -	Shaw Cancer Center
The Role of Pelvic Peritonization in Laparoscopic or Robotic Low Anterior Resection	NCT03699761	Rectum Cancer	Closure of the ... Nonclosure of t...	18 Years - 80 Years	Southwest Hospital, China
Autologous Dendritic Cells, Metronomic Cyclophosphamide and Checkpoint Blockade in Children With Relapsed HGG	NCT03879512	Childhood Gliob...	depletion of re... reoperation cancer vaccine checkpoint bloc...	3 Years - 21 Years	Wuerzburg University Hospital
Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients	NCT05637216	Radiation Induc...	Losartan 25 mil... Placebo	18 Years -	Shaw Cancer Center

Spots Global Cancer Trial Database for reoperation

Every month we try and update this database with for reoperation 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 reoperation

Every month we try and update this database with for reoperation 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 reoperation 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.