Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Pleural Effusion, Malignant

Pleural Effusion

Pleural Diseases

Respiratory Tract Diseases

Pleural Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Anti-Infective Agents

All Drugs and Chemicals

Anti-Bacterial Agents

Antibiotics, Antitubercular

Thoracoscopy with pleurodesis Patients will then undergo standard medical thoracoscopy in the endoscopy center including the use of moderate sedation, prophylactic antibiotics for 1 week and 20F chest tube insertion at the end of the procedure.

Combined thoracoscopy with pleurodesis and pleurx catheter. In the combined procedure group, a PleurxTM tunnelled catheter will be inserted under ultrasound guidance. As this procedure will be done concurrently with thoracoscopy, there is no estimated increase in endoscopy time.

Talc poudrage and tunneled pleural catheter

Thoracoscopy and Pleurx

Thoracoscopy

Devanand Anantham, FCCP

Background:

Malignant pleural effusions form a significant proportion of respiratory and oncology work-load. The efficacy of thoracoscopic talc poudrage which is the current standard of care is limited by lung entrapment which prevents lung re-expansion. Thoracoscopy patients also have significant hospital length of stay because chest tube drainage must continue until the pleural space is dry to effect successful pleurodesis.

Alternative management strategies such as tunnelled pleural catheters (bedside ultrasound-guided) enable outpatient management of pleural effusions but have limited pleurodesis rates and do not offer any chance of getting pleural biopsies.

A prospective randomized controlled trial with two arms i.e. thoracoscopic poudrage alone (standard care) versus combined thoracoscopic poudrage and tunnelled pleural catheters. The tunnelled catheters will be inserted at the time of thoracoscopy in the endoscopy centre under ultrasound guidance. The trial is aimed to be completed within 3 years. Primary end-points will be pleurodesis success. The secondary end-points are hospital length-of-stay, complication rates, analgesia requirements, pain scores and quality-of-life scores. Based on power calculations, we aim to recruit 120 patients in each arm.

Malignant effusions are the 2nd commonest cause of exudative effusions and 75% are due to lung, breast and lymphoma primaries. It is estimated that effusions take up about 20% of pulmonologists' work. About 15% of lung cancers have effusions at presentation and 50% will develop effusions during the course of the illness.

The current standard care of a symptomatic malignant effusion is to perform medical thoracoscopy and talc poudrage pleurodesis to prevent recurrence. Reported pleurodesis success with this technique is about 78%. However, this success rate is limited by the presence of lung entrapment that prevents lung re-expansion and effective pleurodesis. Lung entrapment occurs when there is a visceral pleural tumour peel encasing the lungs or when endobronchial tumour causes lung/lobar collapse. Thoracoscopic pleurodesis also results in significant hospital length of stay as chest tubes must stay in situ until the pleural space is dry.

There is also established data on the use of outpatient tunnelled pleural catheters in malignant effusions. Besides providing effective drainage in cases with entrapped lungs, these catheters also result in spontaneous pleurodesis in 42 to 70% of cases. The attraction of the catheters is that it enables early discharge of patients who already have a terminal illness and an extremely poor prognosis (Prognosis is usually about 3-8 months depending on the primary) However, the pleural catheters do not allow biopsies to be taken from the pleura and the pleurodesis rate is both lower and slower than with talc poudrage.

This project hopes to capitalize on the strengths of both methods ie. talc poudrage via thoracoscopy and indwelling pleural catheters, to increase the success of pleurodesis and to decrease hospital stay. Indwelling catheters may improve the success data by draining effusions associated with entrapped lungs that do not usually achieve pleurodesis with talc poudrage alone. These catheters can be left in patients on a long term basis i.e. \> 6 months. The attraction of the PleurxTM tunnelled catheter system is the low risk of infections, air leaks (because of a one-way valve) and slippage.4-5 This type of study involving combining both modalities has never been reported in the literature. There is no such trial registered under clinicaltrials.gov. Pilot data (\<20 patients) has been previously presented at the American College of Chest Physicians Conference 2006 from Harvard University with promising results.

Current data from our thoracoscopy service in SGH (Jan 2004 to June 2007), shows that our pleurodesis success rate is 78.2%. However, complete success was achieved in 38.1%.7 This data is in keeping with the reported literature and the failures/incomplete successes are attributed to lung entrapment.3 Our data for hospital length of stay is 9.0 ± 4.0 (range 4 to 21) days.

We hypothesized that by combining thoracoscopic talc poudrage with tunnelled catheters, the pleurodesis success rate could be improved by 15% to 93%, complete success to \>75 % and hospital length of stay approximately halved to 5 days or less. To test this hypothesis, we want to conduct a prospective, randomized controlled trial comparing thoracoscopic talc poudrage (standard care) to combined talc poudrage with tunnelled pleural catheters.

Procedure:

Patients who meet inclusion/exclusion criteria will be screened by investigators and trial coordinators. After informed consent has been taken, patients will be randomized to either of the study arms. Randomization will be done through a computer generated random list. Baseline data and quality of life scores will be computed.

Patients will then undergo standard medical thoracoscopy in the endoscopy center including the use of moderate sedation, prophylactic antibiotics for 1 week and 20F chest tube insertion at the end of the procedure. The standard of 4-6 g of sterilized talc will be used for talc poudrage.

In the combined procedure group, a PleurxTM tunnelled catheter will be inserted under ultrasound guidance. As this procedure will be done concurrently with thoracoscopy, there is no estimated increase in endoscopy time. If either group of patients is found to have no gross evidence of malignancy at the time of thoracoscopy (ie. empyemas or tuberculous pleurisy), then they will be withdrawn from the study and notified appropriately.

Patients in the standard therapy arm will emerge from the procedure with a chest tube while the intervention arm will have both a chest tube and a tunnelled catheter. In the standard therapy arm, the chest tube will be removed when there is no further air leak and when drainage drops to ≤ 150 ml/day. After chest tube removal, the patient is fit for discharge. In the intervention arm, the chest tube is removed when air leak stops. There will be no need to wait for fluid drainage to decrease and theoretically, the patient can go home on day 3 or 4 with the tunnelled pleural catheter.

Patients in the thoracoscopy only arm will be reviewed at 1 week in the outpatient clinic by the investigators for suture removal and then again at 1 month for evaluation of radiological success. This is the current standard practice. Quality of life assessment will be also done at the one month visit by the trial coordinator. Subsequent follow-ups will be with medical oncology as per standard practice including visits at about 3 months, 6 months and 1 year.

Concurrent chemotherapy and radiotherapy will be allowed as per current standard of care. Concurrent therapy is unlikely to impact our results because non-small cell lung cancers which form the majority of our referrals have poor pleural effusion response to treatment. This is the basis of why pleurodesis is the current standard of care. Chemosensitive tumours like small cell lung cancers, ovarian cancers and lymphomas are seldom referred for symptom management of pleural effusions unless they are refractory to chemotherapy. Again, these patients will not be affected by concurrent 2nd/3rd line therapy. The small group of patients who may be affected by simultaneous oncological management are those who have a first time diagnosis of a chemosensitive tumour like small cell lung cancer or those with a sensitive adenocarcinoma who are managed with Epidermal Growth Factor Tyrosine-kinase (EGRF) inhibitors. These patients comprise \<5% of our referrals and will have to analyzed separately in subsets to determine their impact on our data. In our pilot review of SGH thoracoscopy data, these cases formed a tiny proportion (1-2 cases) which prevented any meaningful pilot study analysis.

The patients in the intervention combined treatment arm will be reviewed at outpatient clinic either the next day or within 48 hours. They will undergo drainage via the tunnelled catheter. If drainage is less than 150 ml, the PleurxTM catheter will be removed. Otherwise, the patient will be recalled over the next 24-48 hours till such drainage is achieved. If drainage persists for greater than 5 visits, then these patients will be deemed to have an entrapped lung and will need long term pleural catheterization. Subsequent management will be billed to the patient as part of their usual care. In the rare occurrence of a blocked pleural catheter, a fibrinolytic flush (using streptokinase or alteplase) will be used. This will be done using established protocols for management of blocked catheters.

The primary end points will be pleurodesis/pleural catheter success. Complete success is defined in the literature to be no or minimal re-accumulation of pleural fluid at 30 days. Partial success is defined as partial (≤ 50%) re-accumulation of fluid with some resolution of symptoms and the absence of any further therapeutic interventions at 30 days. If any of these conditions are not met then the procedure is deemed to be a failure.

Secondary endpoints are

1. Hospital length of stay. This will be determined primarily by the primary attending physician based on the patient's medical condition. Patients will be considered 'pleurodesis fit for discharge' the day the chest tube is removed. The chest tube will be removed in the absence of pleural space infection or air-leak (i.e. complications) if the effusion drainage drops to ≤ 150 ml/day and if there is lung re-expansion.
2. Complication rates for infections, bleeding, air-leaks/pneumothorax, tumor seeding of the track
3. Pain scores
4. Analgesia/sedation requirements
5. Talc dose required
6. Quality of life analysis using St George's respiratory questionnaire (pre and post), Borg's scale, ECOG and Karnofsky score.
7. Re-admission and repeat procedure rates for complications related to pleurodesis or re-accumulation of fluid. We aim to track the patients for 1 year.

A Prospective, Randomized Controlled Trial for a Rapid Pleurodesis Protocol for the Management of Pleural Effusions

Singapore General Hospital

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Maya Gutierrez, MD

Metastatic pleural effusion is a common complication of late-stage cancer and reduces the quality of life and survival of patients. The survival of patients with recurrent pleurisy by uncontrolled local or systemic treatment is less than 6 months. It is important to develop specific therapies to improve the quality of life and survival of patients with metastatic pleurisy.

Bevacizumab is a monoclonal anti vascular endothelial growth factor (VEGF) which has proven effective in many indications in oncology. Vascular endothelial growth factor (VEGF) is an angiogenic factor which increases endothelial permeability. It plays a central role in many tumors of epithelial origin. In this context, it is legitimate to ask whether an antiangiogenic targeting VEGF may be effective in patients with metastatic pleurisy by decreasing local blood supply and over-permeability.

No study has been interested in the intra-pleural pharmacokinetics of monoclonal antibodies and there are no predictive or prognostic biomarkers for metastatic pleural effusions.

The investigators believe that intrapleural administration of bevacizumab will reduce the pleural vasculature permeability. It will neutralize VEGF present in pleural fluid and reduce the replenishment of effusion due to its prolonged half-life of 21 days.

The investigators therefore propose a phase I study to determine the maximum tolerated dose and the recommended dose for phases II, studying the pharmacokinetics of intrapleural bevacizumab administered by an implantable device after evacuating a symptomatic metastatic pleurisy as part of a mammary carcinoma. The VEGF intrapleural levels and serum will be study and the time until a new puncture. Dyspnea will be evaluated as well as its impact on quality of life.

Intrapleural Bevacizumab After Pleural Drainage in the Context of Breast Cancer

Phase I Study to Determine the Maximum Tolerated Dose and Evaluate the Pharmacokinetics of Intrapleural Bevacizumab After Pleural Drainage in Patients With Symptomatic Malignant Pleural Effusion in the Context of Breast Cancer

Maximum tolerated dose (MTD) according to safety of intrapleural bevacizumab at dose levels of 1 mg/kg, 3 mg/kg and 5 mg/kg administered by pleural catheter after drainage of symptomatic malignant pleural effusion in a context of breast cancer.

Pharmacokinetics of bevacizumab just before administration and 1 hour after treatment on Day 1, and at D15, D30, D60 and D90.

Pleural and serum VEGF levels just before administration and 1 hour after treatment on Day 1, and at D15, D30, D60 and D90.

Response to treatment assessed by the time to new puncture

Measure of the total number of pleural drainage procedures at D15, D30, D60 and D90.

Drainage-free survival and overall survival Evaluation of survival without punction and overall survival

Measure by dyspnoea scale and peak flow at D15, D30, D60 and D90

Quality of life (QLQ-C30) questionnaire according to European Organisation for Research and Treatment of Cancer (EORTC) and FACIT questionnaire Dyspnoea 10 Short Form at D15, D30, D60 and D90 and every 6 month during 2 years

Henri Mondor University Hospital

Institut Curie

Symptoms and General Pathology

Behaviors and Mental Disorders

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Disease Progression

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Lung Diseases

Quality of Life

Malignant Mesothelioma

Channel Blockers

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Piperidine

Enzyme Inhibitors

Patients will receive 200/300 mg of niraparib daily for study period of up to 24 weeks. Patients will be treated until disease progression, withdrawal, death or development of significant treatment limiting toxicity. Niraparib will be supplied in oral formulation as 100 mg capsules. The starting dose of Niraparib will be based upon the patient's baseline body weight and/or platelet count:

Participants with a baseline body weight ≥77 kg and baseline platelet count ≥150 x 109/L will be administered niraparib 300 mg daily.

Participants with a baseline body weight \<77 kg or baseline platelet count \<150 x 109/L will be administered niraparib 200 mg daily.

The dose of Niraparib can be reduced in 100 mg increments, to a minimum of 100 mg, per protocol. Dose escalations are not permitted.

Patients in this arm will be managed symptomatically and will be treated as per the standard of care at each participating site. ASC could involve regular specialist follow up; structured assessment of physical, psychological, and social problems; and appropriate treatment, including palliative radiotherapy and steroids.

Niraparib (\[3S\]-3-\[4-\[7-(aminocarbonyl)-2H-indazol-2-yl\] phenyl\] piperidine \[tosylate monohydrate salt\]) is an orally available, potent, and highly selective PARP1 and PARP2 inhibitor. The excipients for niraparib are lactose monohydrate and magnesium stearate. Niraparib will be supplied in bottles containing 72 capsules of 100 mg. The capsules should be swallowed whole with water. The capsules should not be chewed or crushed and can be taken without regard to meals.

Niraparib Oral Product

ASC could involve regular specialist follow up; structured assessment of physical, psychological, and social problems; and appropriate treatment, including palliative radiotherapy and steroids.

Active Symptom Control

Dean Fennell

Multicentre, 2 arm, open-label UK randomised phase II trial to determine the efficacy of niraparib versus active symptom control (ASC) in patients who have relapsed after previously receiving platinum based systemic therapy. 84 patients will be recruited from approximately 10 UK trial network sites.

Mesothelioma is a cancer that is caused by exposure to asbestos, an environmental contaminant. This cancer is incurable and lacks effective treatment, particularly after initial chemotherapy. There has not been a licenced therapy for mesothelioma since 2003, and no treatment has yet demonstrated an improvement in survival following initial chemotherapy. There is an urgent need to explore more effective approaches to therapy. Targeted treatments offer potential hope for the treatment of mesothelioma. A class of drugs called PARP (Poly Adenosine Diphosphate-ribose polymerase) inhibitors have already been proven to improve the survival of patients with breast and ovarian cancers, that carry specific mutations. Mesothelioma has been shown in a recent trial to respond to this class of agent. Further investigation is warranted to test whether PARP inhibitors could be a new treatment option for patients. As with ovarian cancer studies of the past, the NERO trial will test a PARP inhibitor (niraparib) after successful treatment with chemotherapy. Patients whose tumours shrink or stabilise following chemotherapy are expected to have a greater chance of benefit from niraparib. It's not known if niraparib will be able to improve survival of patients with mesothelioma, or indeed whether or not toxicity could occur without benefit. For that reason, patients will be randomised with a 2:1 chance of receiving the drug. Those patients who do not receive niraparib will be closely monitored for signs of early tumour growth so that they can go on to receive an alternative treatment if necessary. If the NERO trial is positive, this study will lead to the approval of a new medicine for use around the world, one that would extend the life expectancy of patients for the first time following initial chemotherapy. NERO will recruit 84 patients over 12 months. Those randomised to receive niraparib will receive a daily dose of 200 mg or 300mg for up to 24 weeks within the trial.

NERO is a multicentre, 2 arm, open-label UK randomised phase II trial comparing Niraparib versus ASC in patients with previously treated mesothelioma.

Niraparib Efficacy in Patient With Unresectable Mesothelioma

Niraparib Efficacy in Patient With Unresectable Mesothelioma: A Randomised Phase II Trial of Niraparib Versus Active Symptom Control in Patients With Previously Treated Mesothelioma

IPD will be made available, including data dictionaries, for approved data sharing requests. Individual participant data will be shared that underlie the results after de-identification and normalisation of information (text, tables, figures, and appendices). The study protocol and statistical analysis plan will also be available. Pseudonymised participant data within the clinical trial dataset will be available for sharing via controlled access by authorised Southampton Clinical Trials Unit (SCTU) staff. The request for data access will need to detail the specific requirements and the proposed research, statistical analysis, publication plan and evidence of research group qualifications. Data will be shared once all parties have signed relevant data sharing documentation covering SCTU conditions for sharing and if required, an additional data sharing agreement from the sponsor. Proposals should be directed to ctu@soton.ac.uk.

Response, progression-free and overall survival will be correlated with somatic alteration of HR genes

Progression-free survival is the determined by modified RECIST (pleural disease), RECIST 1.1 (for non-pleural disease), investigator reported progression or death from any cause (whichever event comes first)

Time from randomisation to death from any cause

The best overall response is the best response recorded from the start of treatment until disease progression or death

Stable disease, partial or complete response

Time from complete or partial response (where this occurs) until progression or death

Assessed by summarising the percentage of the received dose relative to the intended dose at each cycle

Summary statistics and listings will be reported for patients in the safety population and will be summarised by treatment arm with classification by the latest version of MedDRA. Grade will be reported on the CTCAE toxicity scale (version 5.0). Both all cause and treatment related or emergent AEs will be included in the analysis.

University of Southampton

British Lung Foundation

University Hospital Southampton NHS Foundation Trust

Immune System Diseases

Ear, Nose, and Throat Diseases

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Hypersensitivity

Neurofibromatosis 2

Neurofibromatosis Type 2

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Immunosuppressive Agents

Immunologic Factors

This is a multicenter, open label, phase II study of everolimus as a second or third line therapy for the treatment of advanced malignant pleural mesothelioma, which will also evaluate Merlin/NF2 loss as a biomarker to predict sensitivity to everolimus. Patients who have disease progression after one or two prior chemotherapy regimens will be eligible. In the first stage of this design, 19 patients will be accrued. If 6 or less patients among the first 19 patients show clinical benefit, then the study will be terminated and declared negative. If 7 or more patients show clinical benefit, than an additional 20 patients will be accrued to the second stage. At the end of the study, if 17 or more patients show clinical benefit out of a total of 39 patients enrolled, the regimen will be considered worthy of further investigation.

Everolimus will be administered at a dose of 10mg orally once daily continuously. Dose reduction may be required depending on the type and severity of toxicity encountered. One cycle will be considered 28 days. Patients will have CT scans to evaluate for response after cycle 1 and cycle 2, and then every two cycles thereafter.

everolimus

Lee Krug, MD

For patients with malignant pleural mesothelioma that has grown despite treatment with standard chemotherapy, no treatment has yet proven beneficial. The purpose of this study is to find out what effects, both good and bad, that everolimus has on the cancer. Everolimus works by blocking a protein that helps the cancer grow. The goal of this clinical research study is to learn if the study drug everolimus can shrink or slow the growth of mesothelioma. The safety of this drug will also be studied. The patients' physical state, changes in the size of the tumor, and laboratory findings taken during the study will help us decide if everolimus is safe and effective.

Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity

Phase II Study of Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Novartis Pharmaceuticals

Dana-Farber Cancer Institute

University of Pennsylvania

Memorial Sloan Kettering Cancer Center

This is a multicenter, open label, phase II study of everolimus as a second or third line therapy for the treatment of advanced malignant pleural mesothelioma, which will also evaluate Merlin/NF2 loss as a biomarker to predict sensitivity to everolimus. Patients who have disease progression after one or two prior chemotherapy regimens will be eligible. In the first stage of this design, 19 patients will be accrued. If 6 or less patients among the first 19 patients show clinical benefit, then the study will be terminated and declared negative. If 7 or more patients show clinical benefit, than an additional 20 patients will be accrued to the second stage. At the end of the study, if 17 or more patients show clinical benefit out of a total of 39 patients enrolled, the regimen will be considered worthy of further investigation.

everolimus: Everolimus will be administered at a dose of 10mg orally once daily continuously. Dose reduction may be required depending on the type and severity

Patients Getting Everolimus

Age, Categorical

Sex: Female, Male

Dr. Lee Krug

Stable Disease

Progression of Disease

To Determine the Rate of Clinical Benefit (i.e. Rate of Complete or Partial Response Plus Stable Disease) at 16 Weeks for Patients With Malignant Mesothelioma Treated With Everolimus as Second or Third Line Therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Prospective, Randomized Controlled Trial for a Rapid Pleurodesis Protocol for the Management of Pleural Effusions	NCT00758316	Malignant Pleur...	Thoracoscopy an... Thoracoscopy	18 Years -	Singapore General Hospital
Intrapleural Bevacizumab After Pleural Drainage in the Context of Breast Cancer	NCT02250118	Pleural Effusio... Breast Cancer	Bevacizumab	18 Years -	Institut Curie
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust
A Prospective, Randomized Controlled Trial for a Rapid Pleurodesis Protocol for the Management of Pleural Effusions	NCT00758316	Malignant Pleur...	Thoracoscopy an... Thoracoscopy	18 Years -	Singapore General Hospital
Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity	NCT01024946	Malignant Pleur...	everolimus	18 Years -	Memorial Sloan Kettering Cancer Center
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust

Spots Global Cancer Trial Database for pleural

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

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