Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Breast Neoplasms

Neoplasm Metastasis

Liver Neoplasms

Breast Diseases

Skin Diseases

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

All Drugs and Chemicals

Hematinics

Complement System Proteins

Liver Extracts

Surgical intervention by liver resection, ablation or stereotactic body radiotherapy as complement to oncological treatment

Surgical intervention

Control

Oskar Hemmingsson, MD, PhD

Malin Sund, MD, PhD

Anne Andersson, MD, PhD

Breast cancer is the second most common cancer in Sweden with an incidence of 8000 per year. The role of surgery for distant breast cancer metastasis beyond local lymph nodes remains controversial even though some reports suggest there might be a survival benefit from resection of oligometastases in the liver.

The purpose of this multicentre randomized clinical trial is to evaluate local treatment for breast cancer liver metastases, compared to systemic oncological treatment only. The primary endpoint is time to death from any cause, which will be compared using cox proportional hazard regression. The secondary endpoints are three years survival, progression-free survival, median overall survival and quality of life. The aim is also to evaluate overall safety and predictive factors for survival during oncological and surgical treatment. The overall purpose is to ameliorate treatment for advanced breast cancer.

BreCLIM-2 - A RCT Investigating Local Treatment for Breast Cancer Liver Metastases

Breast Cancer Liver Metastases-2 - A Multicentre Randomized Clinical Trial Investigating Local Treatment for Breast Cancer Liver Metastases

Uppsala University

Karolinska Institutet

Linkoeping University

Lund University

Göteborg University

Umeå University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma, Renal Cell

Kidney Neoplasms

Carcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Renal Cell Carcinoma

Surgical intervention with collection of tissue material

TRICARD Thibault

MALOUF Gabriel

LANG Hervé

BERGERAT Sébastien

STORY Fleur

MUNIER Pierre

An exploratory analysis of the expression of MFI2-AS1 will be performed at the plasma level with the objective of comparing this expression with tumor tissue. The objective would be to be able to use long non-coding RNA as a biomarker for diagnosis before tissue analysis and for patient follow-up. In addition, correlations will be made between tumor expression of MFI2-AS1 and genetic and immune alterations in tumors in order to better clarify the link between the expression of this long non-coding RNA and the characteristics of the tumor and of the tumor. tumor microenvironment.

Prospective Validation of the Prognostic Value of Long Non-coding MFI2-AS1 RNA in Localized Clear Cell Kidney Cancers

To assess the link between tumor expression of MFI2-AS1 in patients with localized clear cell kidney carcinoma and the occurrence of relapse

University Hospital, Strasbourg, France

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Esophageal Neoplasms

Sarcoma

Lung Neoplasms

Mesothelioma

Mesothelioma, Malignant

Thymoma

Thymus Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neoplasms, Connective and Soft Tissue

Head and Neck Neoplasms

Esophageal Diseases

Adenoma

Neoplasms, Mesothelial

Pleural Neoplasms

Lymphatic Diseases

Esophageal Cancer

Soft Tissue Sarcoma

Malignant Mesothelioma

Antineoplastic Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Analgesics

Vaccines

Cyclophosphamide

Immunomodulating Agents

Celecoxib

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Allogeneic tumor cell vaccine + chemotherapy

Subcutaneous injection monthly for 6 months

Allogeneic Tumor Cell Vaccine (K562)

cyclophosphamide

David S Schrump, M.D.

Background:

- Certain types of lung, esophageal, or thymic cancers and mesotheliomas have specific antigens (protein molecules) on their surfaces. Research studies have shown that giving a vaccine that contains antigens similar to these may cause an immune response, which may keep tumors from growing. Researchers are also interested in determining whether the chemotherapy drug cyclophosphamide and the anti-inflammatory drug celecoxib may help the vaccine work better, particularly in patients with lung cancer.

Objectives:

- To evaluate the safety and effectiveness of tumor cell vaccines in combination with cyclophosphamide and celecoxib in patients with cancers involving the chest.

Eligibility:

- Individuals at least 18 years of age who have had surgery for small cell or non-small cell lung cancer, esophageal cancer, thymoma or thymic carcinoma, and malignant pleural mesothelioma.

Design:

* Following recovery from surgery, chemotherapy, or radiation, participants will have leukapheresis to collect lymphocytes (white blood cells) for testing.
* Participants will receive celecoxib and cyclophosphamide to take twice a day at home, 7 days before the vaccine.
* Participants will have the vaccine in the clinical center (one or two shots per month for 6 months), and will stay in the clinic for about 4 hours after the vaccine. Participants will keep a diary at home of any side effects from the vaccine, and will continue to take cyclophosphamide and celecoxib.
* One month after the sixth vaccine, participants will provide another blood sample for testing, and if the tests are satisfactory will return to the clinic every 3 months for 2 additional vaccines.
* Participants will return to clinic for follow-up physical examinations, lab tests, and scans every 3 months for 2 years and then every 6 months for up to 3 years.

Background:

During recent years, the cancer-testis (CT) antigens have emerged as attractive targets for cancer immunotherapy. Whereas lung and esophageal cancers, as well as malignant pleural mesotheliomas express a variety of CT antigens, immune responses to these antigens appear uncommon in patients with these malignancies, possibly due to low-level, heterogeneous antigen expression, as well as immunosuppressive regulatory T cells. Our published studies indicate that numerous CT antigens can be induced in tumor cells by DNA demethylating agents and histone deacetylase (HDAC) inhibitors. Conceivably, vaccination of cancer patients with allogeneic tumor cells expressing high levels of multiple CT antigens in combination with depletion of T regulatory cells will induce broad immunity to these antigens. In order to examine this issue, patients with lung and esophageal cancers, thymic neoplasms, primary thoracic sarcomas, and malignant pleural mesotheliomas will be vaccinated with irradiated K562 erythroleukemia cells expressing GM-CSF (K562-GM) following completion of appropriate combined modality therapy. Vaccines will be administered in conjunction with metronomic oral cyclophosphamide (50 mg PO BID x 7dq 14d), and celecoxib (400 mg PO BID). Serologic responses to a variety of recombinant CT antigens as well as cell-mediated recognition of autologous tumor cells and EBVtransformed B cells will be assessed before and after vaccination.

Objective:

-To assess the safety of K562-GM allogeneic tumor cell vaccines in combination with oral metronomic cyclophosphamide and celecoxib in thoracic oncology patients.

Eligibility:

* Patients with histologically or cytologically proven small cell or non-small cell lung cancer, esophageal cancer, thymoma or thymic carcinoma, primary thoracic sarcomas, and malignant pleural mesothelioma with no evidence of disease (NED) or minimal residual disease (MRD) in the primary site following standard multimodality therapy.
* Patients must be 18 years or older with an ECOG performance status of 0 - 2, without evidence of unstable or decompensated myocardial disease. Patients must have adequate pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted; pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no immunosuppressive medications except inhaled corticosteroids at the time vaccination commences.
* Patients must have a platelet count greater than 100,000, an ANC equal to or greater than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function as evidenced by a total bilirubin of \<1.5 x upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2) at the time vaccination commences.

Design:

* Following recovery from standard combined modality therapy, patients with no evidence of disease or minimal residual disease will be vaccinated via subcutaneous intradermal injection with 1x10(8) irradiated K562-GM-tumor cells periodically over 6 months. Sterility, potency and identity of the vaccines preps will be confirmed before administration.
* Vaccines will be administered in conjunction with metronomic oral cyclophosphamide and celecoxib.
* Systemic toxicities, and immunologic response to therapy will be recorded. Pre and post vaccination serologic responses to a standard panel of CT antigens as well as cell mediated responses to epigenetically-modified autologous EBV-transformed B and autologous tumor cells (if available) will be assessed before and after vaccination.
* Numbers/percentages and function of T regulatory cells in peripheral blood will be assessed before, during, and after vaccinations.
* Patients will be followed in the clinic with routine staging scans until disease recurrence.
* As the exact set of comparisons and analyses to be performed will be determined following completion of the trial, and will be based on limited numbers of patients, the analyses will be considered exploratory and hypothesis generating rather than definitive.
* Approximately 25 patients will be accrued to this trial.

Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas

Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib as Adjuvant Therapy for Lung and Esophageal Cancers, Thymic Neoplasms, Thoracic Sarcomas, and Malignant Pleural Mesotheliomas

If 25 patients are enrolled and the true probability of a grade 3 or worse toxicity (of any sort) were 20%, then the probability of having 4 or more patients with this occurring is 76.6%. On the other hand, if the combination was very safe and the true probability of a grade 3 or worse toxicity was 5%, then the probability of having 4 or more patients with this occurring would be 3.4%. Thus, if 25 patients were treated, the combination may be considered to have potentially lower safety than tolerable if 4 or more patients experience grade 3 or worse toxicity.

Perform exploratory analyses which investigate immunologic responses to a panel of CT antigens in vaccinated patients.

Measure T regulatory cells at baseline and at the conclusion of treatment. The difference, or the relative difference, in the values at the two time points will be obtained, and tested to determine if the difference is equal to zero. If a paired t-test is able to be used, with at least 20 evaluable patients, there is 81% power to detect a change equal to 3/4ths of a standard deviation of the change at the two-sided 0.025 significance level.

National Cancer Institute (NCI)

Lymphedema

Breast Cancer Lymphedema

Postoperative Complications

Chronic Graft Versus Host Disease

Central Nervous System Depressants

Other Dietary Supplements

Benzocaine

Tannic Acid

According to the pragmatic study design, neither the diagnostic workup nor the surgery will be standardized in order to offer surgeons considerable leeway on how to perform lymphatic surgery, which resembles the flexibility in usual care. The key aspects of the preoperative workup and the surgery including the number of LVAs (Lymphovenous Anastomosis), harvesting of lymph nodes ("donor site"), time of surgery, and practical details will be registered.

CDT (Conservative Complex Physical Decongestion Therapy) will be performed as in usual care, following the pragmatic study design. The key aspects like frequency of lymphatic drainage, time when lymphatic drainage is performed and time and class of compressive garments are used will be documented. CDT incorporates two stages of treatment. The first treatment phase (intensive phase) entails skincare, MLD (manual lymphatic drainage), exercises aimed at improvement of mobility/range of motion in the shoulder, elbow or wrist joints, and compression therapy through bandaging. Most patients undergo this phase shortly after the diagnosis of LE. CDT in the second phase (maintenance phase) aims to maintain the achieved limb volume/ circumference reduction through compression with therapeutic elastic compression garment for the arm. Skincare, mobility exercises and MLD is continued in this phase if needed

LVA (Lymphovenous Anastomosis) and VLNT (Vascularised Lymph Node Transfer) are two advanced microsurgical techniques that are increasingly implemented in clinical practice in specialized centers and that are already carried out after health insurance application according to local standard of care. They have been studied in their respective mode of action as well as in their effectiveness in treating chronic BCRL (Breast Cancer-Related Lymphedema) in a multitude of mostly observational and single center studies with highly encouraging results. Patients in the interventional arm A will receive surgery with one of the two approaches or a combination of both, in a one or two-stage method, at the discretion of the treating surgeon. Depending on local standards one or both of the above might be combined with liposuction to the affected arm in a one or two-stage approach as well.

Surgical Intervention

Patients randomized to the control arm will receive CDT (Conservative Complex Physical Decongestion Therapy), which currently is considered as the best available standard of care. For this, patients will be referred to one of the dedicated LE (physical/skin) therapy clinics, if not already treated by one, according to their place of residence for continuation of standard conservative therapy. Recommendations to the procedures and treatment frequency of the conservative therapy will be made, but CDT will be done at the discretion of the treating physiotherapist.

Conservative Complex Physical Decongestion Therapy

Elisabeth Kappos, PD Dr. med.

Andrea Pusic, Prof. Dr. med.

Erin Taylor, Dr. med.

Justin M. Sacks, Prof. Dr.

Eduardo Gonzalez, Dr. med.

Madeleine Mischitz, Dr.

Matthias Rab, Dr.

Phillip Blondeel, Prof. Dr.

Anne Karoline Groth, Dr. med.

Josh Vorstenbosch, MD PhD FRCSC

Anna Towers, Dr.

Kathryn V. Isaac, Asst. Prof. Dr.

Katrin Seidenstücker, Dr.

Raymund Horch, Prof. Dr.

Björn Behr, Prof. Dr. med.

Christoph Hirche, Prof. Dr. med.

Steffen Eisenhardt, Prof. Dr. med.

Gunther Felmerer, Prof. Dr. Med.

Ulrich Kneser, Prof. Dr. med.

Lukas Prantl, Prof. Dr. med.

Norbert Heine, Dr. med.

Efterpi Demiri, Prof. Dr. med.

Dimitrios Dionysiou, Dr. med.

Benedetto Longo, Dr. med.

Giuseppe Visconti, Dr. med.

Shao Shan Qiu, Dr.

Maximilian Vlad Muntean, Dr. med.

Gemma Pons, Dr.

Martin Halle, Dr. med.

Maria Mani, Dr. med.

Yves Harder, Prof. Dr. med.

Jan Plock, Prof. Dr. med.

Daniel Kalbermatten, Prof. Dr. med.

Pietro di Summa, PD Dr. med.

Florian Jung, Dr. med.

Nicole Lindenblatt, Prof. Dr. med.

The aim of this study is to test whether lymphatic surgery provides better QoL (assessed with the Lymph-ICF-UL, (Lymphedema Functioning Disability and health questionnaire for upper limb lymphedema)) 15 months after randomization (and therefore about one year after surgery) compared to conservative treatment only for patients with chronic lymphedema (LE)

To date, conservative complex physical decongestion therapy (CDT) is the gold standard for BCRL (breast cancer related lymphedema) and includes manual lymphatic drainage, local compression with bandages and garments, physical exercises and meticulous skin care. It is, however, too often ineffective to prevent stage progression in curing BCRL and purely symptomatic. Lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) are two surgical techniques that, in contrast to CDT, are able to actually address the underlying causes and eventually restore the lymphatic drainage. LVA achieves this by creating numerous bypasses between lymphatic vessels and venules allowing the drainage of excessive fluid within the subcutaneous tissues into the venous system, while VLNT usually brings functioning lymph nodes to an area devoid of lymph nodes or with dysfunctional lymph nodes, thus enabling the spontaneous development of new lymphatic pathways. Both techniques have shown very promising results with low complication rates and improved Quality of Life (QoL) for the patients. However, no multicentric randomized controlled trial (RCT) has yet prospectively evaluated the superiority of these surgical techniques over CDT alone, limiting patient's access to most effective treatment available. Requests for cost reimbursement must still be submitted to insurance companies in most countries and are often rejected, thus delaying surgical treatment and resulting in prolonged suffering of affected patients. This is untenable seeing as affected patients suffer from a heavy physical, psychological and financial burden. This pragmatic, randomized, multicenter trial aims to establish a solid scientific basis assessing the superiority of surgical treatment over CDT alone.

Pragmatic, randomized, international, multicenter superiority trial

The LYMPH Trial - Surgical Versus Conservative Complex Physical Decongestion Therapy for Chronic Breast Cancer-Related Lymphedema

The LYMPH Trial - Surgical Versus Conservative Complex Physical Decongestion Therapy for Chronic Breast Cancer-Related Lymphedema: A Pragmatic, Randomized, Multicenter Superiority Trial

The LYMPH-ICF-UL-Questionnaire (Lymphedema Functioning Disability and health questionnaire for upper limb lymphedema) is a widely used, rigorously developed, and validated patient-reported outcome (PRO) instrument for chronic breast cancer-related lymphedema. It assesses the impairments in function, activity limitations and participation restrictions of patients with upper limb lymphedema (LE). Consisting of 29 items (questions) across five different domains, each item is scored on a VAS (visual analog scale) ranging from 0 to 10. The total score on the LYMPH-ICF is equal to the sum of the item scores divided by the total number of answered items. A higher score on the Lymph-ICF indicates a greater impact on the functioning in daily life related to upper limb LE. This questionnaire helps determine if lymphatic surgery improves quality of life and patient satisfaction compared to conservative therapy.

The Lymph-Q Upper Extremity Module is a new PROM (patient-reported outcome measure) developed to assess patient reported outcomes of BCRL in a concept-driven approach. The complete questionnaire contains 68 questions covering the patient-relevant topics Health-related quality of life (arm appearance, arm function, arm symptoms, psychological), experience of care (information), and treatment (arm sleeve).

The questionnaire is used to determine whether lymphatic surgery provides better quality of life and patient satisfaction compared to conservative therapy.

The 5-level EQ-5D version (EQ-5D-5L) consists of the EQ-5D descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions (5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems) resulting in a 1-digit number that expresses the level for that dimension. The digits for each dimension can be combined into a 5-digit number that describes the patient's health state.

The questionnaire is used to determine whether lymphatic surgery provides better quality of life and patient satisfaction compared to conservative therapy.

The pain score consists of a VAS (visual analog scale) ranging from 0 (i.e. no pain) to 10 (i.e. worst pain). The VAS was published by the Yale University.

It is used to determine whether lymphatic surgery provides better quality of life and patient satisfaction compared to conservative therapy.

Safety is assessed via a rigorous and detailed examination of (serious) adverse events.

For the surgery group only, safety is assessed via a rigorous and detailed examination of complications of surgery. Grading is according to the modified classification of Clavien-Dindo, categorizing them into five levels ranging from minor deviations to life-threatening events.

The assessment will cover both surgical stages in case of two-staged lymphedema (LE) surgery.

The frequency of lymphangitic events (erysipelas) is closely monitored. Lymphangitic events are defined as skin infections at the lymphedema site(s) which can be treated with oral or intravenous antibiotics. The type of antibiotic given, the application form, type of hospital stay and necessity of a surgery will be assessed.

Arm volume is determined by measuring the circumference of each arm at 10 cm intervals from the wrist to the axilla. The volume of each arm segment is calculated using a truncated cone model, and percentage edema volume is derived from the volume difference between the affected and unaffected arms. Both relative (relative to the unaffected arm) and absolute (volume reduction of the affected arm at the next measurement) volume change are calculated, corrected for BMI and differences between dominant and non-dominant arms.

The frequency of lymphatic drainage before the start of the study and between the study's follow-up visits is assessed.

To determine the burden on patients, the total number of breast-/arm-related operative procedures including the second stage intervention in case of two-staged surgery until the end of the 24-month follow-up is assessed by screening patient charts, interviewing patients during follow-up and corresponding with the family practitioners if indicated.

To determine the burden on patients, the length of lymphedema-related hospital stay(s) is recorded following the randomization until discharge and the cumulative number of days the patient is hospitalized until two years after randomization. This information is obtained from the hospital patient record database where available or manual chart review and from interviews of the patients during follow-up.

To determine the burden on patients, the number of LE-related outpatient visits including visits at family doctor, study site, emergency room or other specialist physicians is assessed from randomization until the 24 months follow-up.

To determine the burden on patients, the lymphedema-related change in the ability to work is assessed by the number of missed working days and hours until the 24 months follow-up and extended follow-up.

To perform an economic evaluation, information regarding the condition-related medical resource use, healthcare costs, indirect costs, productivity losses, and incremental cost-effectiveness (quality-adjusted life-years) is collected.

The information is based on the responses to the EQ-5D-5L questionnaire, the questions asked under burden on patients, and on other medical resource information recorded in the trial primarily for clinical purposes, at the respective visits. In addition, direct extraction of breast cancer-related lymphedema-related in- and outpatient costs, and corresponding key resource use parameters, are collected from the hospital administration systems of the participating Swiss sites, once at the 2 year follow-up visit .

Swiss National Science Foundation

Rising Tide Foundation

Krebsforschung Schweiz, Bern, Switzerland

University Hospital, Basel, Switzerland

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BreCLIM-2 - A RCT Investigating Local Treatment for Breast Cancer Liver Metastases	NCT04079049	Breast Cancer Liver Metastase...	Surgical interv... Control	18 Years -	Umeå University
BreCLIM-2 - A RCT Investigating Local Treatment for Breast Cancer Liver Metastases	NCT04079049	Breast Cancer Liver Metastase...	Surgical interv... Control	18 Years -	Umeå University
Prospective Validation of the Prognostic Value of Long Non-coding MFI2-AS1 RNA in Localized Clear Cell Kidney Cancers	NCT04946266	Kidney Cancer	Surgical interv...	18 Years -	University Hospital, Strasbourg, France
Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas	NCT01143545	Lung Cancer Esophageal Canc... Malignant Pleur... Sarcoma Thymic Carcinom...	Allogeneic Tumo... Celecoxib cyclophosphamid...	18 Years -	National Institutes of Health Clinical Center (CC)
The LYMPH Trial - Surgical Versus Conservative Complex Physical Decongestion Therapy for Chronic Breast Cancer-Related Lymphedema	NCT05890677	Lymphedema, Bre...	Surgical Interv... Conservative Co...	18 Years -	University Hospital, Basel, Switzerland

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