Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Frailty

50-66Gy/ 24 fractions, inhomogeneous dose distribution Photon therapy

50-66Gy/ 24 fractions, inhomogeneous dose distribution Proton therapy

50-66Gy/ 24 fractions, inhomogeneous dose distribution photon therapy

Photon

50-66Gy/ 24 fractions, inhomogeneous dose distribution proton therapy

Proton

Tine Schytte, PhD

Ditte S Møller, PhD

Aim To test if proton therapy can improve survival compared to photon therapy in patients with locally advanced NSCLC who are not candidates for standard definitive chemo-radiotherapy.

Hypothesis The trial hypothesis is that proton therapy is less toxic than photon therapy in fragile patients and that this difference will mitigate to a difference in overall survival.

Design Multicentre, randomized phase II study 1:1 Sample size 182 patients (91 in each arm) Treatment Radiotherapy (inhomogeneous dose distribution) 50 Gy/ 24 fraction Endpoint Primary: Overall survival at 12 months Secondary: progression free survival, time to loco-regional and distant failure, pattern of failure, acute and late toxicity, quality of life, patient compliance.

Study aim To evaluate whether a heterogeneous and hypo-fractionated definitive radiotherapy schedule delivered using proton (PT) can improve OS compared to photon (XT) in patients with LA_NSCLC not candidates for standard, long-course chemo-radiotherapy.

Primary endpoint

* OS at 12 months Secondary endpoints
* Progression-free survival
* Time to loco-regional failure
* Time to distant failure
* Pattern of failure
* Acute toxicity
* Late toxicity
* Persistent acute grade 2 or higher lung or esophageal toxicity
* Radiotherapy compliance
* Hospitalization during and up to 6 months after treatment
* Patient reported outcome measures at base-line and during follow-up Exploratory endpoints
* Heart toxicity evaluated by changes in cardiac biomarkers
* Changes in lymphocyte counts

Study design The study is designed as a prospective randomized multicentre phase II study. It includes patients with inoperable locally advanced NSCLC (stage IIB-IIIB) not candidates for standard concomitant chemotherapy. Patients are treated with radiotherapy in 24 fractions, 5 fractions a week. Dose prescription is inhomogeneous with 50 Gy to the clinical target volume (CTV).

Patients will be randomized 1:1 between XT or PT. It will thus be open-label to the patient and the treating physicians.

Systemic therapy Patients can receive induction therapy with platinum doublet. Randomization and stratification Patients will be randomized (1:1) to either XT or PT. Randomization will be performed centrally using an online 24-hour web-based system maintained by the Clinical Trial Office at Odense University Hospital, ensuring allocation concealment to the clinical investigators. Randomization will be stratified for referring centre and histology (squamous cell carcinoma versus other non-squamous cell carcinoma).

Study sample size The study will use a three-outcome design to examine whether use of PT results in improved OS compared to XT. Preliminary data from the HERAN trial indicate that the patient population (patients not candidate for definitive chemo-radiotherapy) will have a 60% survival rate at 12 months following heterogeneously hypo-fractionated XT. We expect that the patients in HERAN will be representative of the patient population in HERAN2, and that survival in the XT arm will be comparative. A 15%-point improvement in 12 months survival (to 75%) is considered clinically relevant in order to definitely take PT forward for this patient group. 174 patients (87 in each arm) will be needed to provide 80% power to demonstrate this difference at 10% (one-sided) significance level, based on simple comparisons of proportions. Due to the fragile patient population at dropout of 5% is expected, and in order to take this into account 182 patients (91 in each arm) will be included.

It is recognized, however, that a smaller difference (corresponding to a lower level of statistical significance) might still be clinically relevant and warrant further examination of PT for this patient group; provided that the treatment is otherwise tolerable for patients (as measured by toxicity, patient uptake, impact on QoL, and post-treatment hospitalizations rate). Hence a phase II three-outcome screening design is used to form the basis of the decision-making process following the completion of the study, based on the work of Hong \& Wang (50) and e.g. used in the SYSTEMS-2 trial (51). The proposed sample size will allow for 90% power to detect a 15%-point difference at 20% (one-sided) significance level; or alternatively 80% to detect a 12%-point difference at the same (80%) significance level. A study outcome in favor of PT at the one-sided 20% level - but not the one-sided 10% level - will thus be considered positive only if other study data supports the use of PT.

Study time frame We consider it realistic to enroll 182 patients from all Danish radiotherapy centres in a period of 3 years.

Data management Data will be filed and stored using electronical 'case report forms' (CRFs) in a local database provided by Open Patient Data Explorative Network (OPEN). The informed consent will ensure the investigators/co-investigators access to the patient's electronic records and collect information at baseline and follow-up.

The clinical data will include: date of birth, gender, smoking history, co-morbidity, weight, TNM stage, histology, performance status, status on prescribed drug, as well as baseline blood test. Relevant for handling of the patients. The data will be obtained from patient file and handed over to the researcher.

All dose plans used for patient treatment, including adapted plans, are exported to the national dose plan bank (DCMCollab), from where doses to tumor, lymph nodes and OAR are extracted for analysis.

Baseline PET-CT scans, as well as any CT or PET-CT scans acquired at time of disease recurrence should also be transferred to the dose plan bank.

The data management system ensures compliance with current legislation and regulations on data handling and data safety.

Withdrawal from the study

A patient may be withdrawn from the study if any of the following events occur:

* If, in the opinion of the investigator, withdrawal is necessary for medical reasons
* Major protocol violation according to national GCP guidelines
* Major technical failure according to national GCP guidelines
* Informed consent withdrawal In case of a withdrawal, another patient will be enrolled (with a new patient number). The withdrawn patient will be accounted for in the statistical analysis. The reason for withdrawal should be clearly described, whenever possible and regardless of the reason for withdrawal. Relevant data should be obtained, and all relevant assessments should be completed, preferably according to the schedule for the final assessment. The CRF in REDCap should be completed.

Screening log All centres will keep a screening log of all patients informed about the trial and in case the patient decline to participate, the reason for declining is noted.

Radiotherapy treatment planning is described in detail. Target dose All treatments are delivered in 24 fractions, 5 fractions per week. For the nominal plan, the mean dose to GTV-T and GTV-N should be increased as much as allowed by normal tissue dose constraint but not exceeding a mean dose of 66 Gy in 24 fractions.

Quality assurance is planned in detail for Target and OAR delineation Treatment planning During the trial, dose volume histograms for the included patients will be analyzed yearly (at minimum) via the national dosebank database to avoid systematic discrepancies between centres.

Study procedures and follow-up Evaluations before and during treatment Patients will be evaluated, and treatment toxicity will be registered at baseline and twice during the course of radiotherapy. If the patient has symptoms which need clinical assessment, the patient will get an appointment with a physician.

Baseline registration consists of baseline patient characteristics. Treatment compliance should be recorded at the end of treatment. Patient reported outcome measures will be scored using EORTC C30 and LC13.

Follow-up Patients will be seen every 3rd month during a follow up period of 24 months and thereafter every 6th month until end of study. During the first 24 months, the patient will be examined every 3rd month with a CT-scan and afterwards twice a year. Lung function test will be performed at 3 months and hereafter yearly. An ECG will be performed at baseline as well as at 3 and 12 months. Clinical examinations and evaluation of toxicity will be performed at every occasion. Disease recurrence, site of recurrence, as well as death should be reported; this may be done by local investigators by review of electronic patient records once a year. End of study is 5 years after commencement of radiotherapy.

The follow-up will be performed at local department of oncology.

Heterogeneously Hypofractionated Radiotherapy for Locally Advanced NSCLC

HERAN2 Heterogeneously Hypofractionated Radiotherapy for Locally Advanced NSCLC A Randomised Multicentre Phase II Feasibility Study

Overall survival 12 months after randomization

Number of patients with acute toxicity, defined as any radiotherapy related toxicity occurring up to 9 months after randomization

Number of patients with late toxicity, defined as any radiotherapy related toxicity occurring later than 9 months after randomization.

Any progression or recurrence (locoregional or distant) as well as death from any cause, whatever occurs first, will be considered as events

First site of failure will be divided in primary tumour, bulky lymph nodes, non-bulky lymph node targets, regional lymph nodes not included in target delineation/ irradiated, and distant failures.

Changes in Brain Natriuretic peptide (BNP),Troponin T (TnT) and I (TnI) from baseline up to 12 months after radiotherapy

Changes in Troponin I (TnI) from baseline up to 12 months after radiotherapy

Changes in Troponin T (TnT) from baseline up to 12 months after radiotherapy

Changes in lymphocyte count before and after RT

Circulating tumour DNA detection before RT and during follow up

Odense University Hospital

Professor, Consultant

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Nasopharyngeal Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

The participants received photon: 56 Gy/28 Fx for high-risk area(CTVhigh), 50.4 Gy/28 Fx for lower neck low-risk area(CTVlow), plus carbon ion: 15-17.5 GyE/5 Fx for boost for visible tumors.

The participants received proton: 56 GyE/28 Fx for high-risk area(CTVhigh), 50.4 GyE/28 Fx for lower neck low-risk area(CTVlow), plus carbon ion: 15-17.5 GyE/5 Fx for boost for visible tumors.

Same dose and fractionation will be used in both arms.

Carbon ion

Lin Kong, MD

Jiyi Hu, MD

Jiade J Lu, MD

Jiade Lu, MD

The purpose of this study is to compare the toxicity and therapeutic efficacy of proton or photon combined with carbon ion radiotherapy for newly diagnosed nasopharyngeal carcinoma.Participants will be randomized to 2 arms. Arm 1, participants received photon combined with carbon ion radiotherapy group, Arm 2, participants received proton combined with carbon ion radiotherapy.

The purpose of this study is to compare the toxicity and therapeutic efficacy of photon or proton combined with carbon ion radiotherapy for newly diagnosed nasopharyngeal carcinoma.Participants will be randomized to 2 arms. Arm 1 participants received photon combined with carbon ion radiotherapy (photon: 56 Gy/28 Fx, plus carbon: 15-17.5 gray equivalent \[GyE\]/5 Fx for boost). Arm 2, participants received proton combined with carbon ion radiotherapy (proton: 56 GyE/28 Fx, plus carbon: 15-17.5 GyE/5 Fx for boost). Adverse events will be documented according to CTCAE v4.03.The response of treatment will be evaluated according to RECIST criteria.

Proton Versus Photon Radiotherapy for Nasopharyngeal Carcinoma

A Randomized Phase II Trial Evaluating Toxicity and Efficacy Between Proton and Photon for Nasopharyngeal Carcinoma

Individual participant data including baseline characteristics, treatment information and follow-up data on toxicity, survival and disease control will be shared.

CTCAE refers to Common Terminology Criteria for Adverse Events, which is one of the most frequently used criteria for toxicity grading after anti-cancer treatment.

Acute and late toxicities induced by radiation therapy other than xerostomia.

Shanghai Proton and Heavy Ion Center

Executive Vice-President

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Amino Acids

Gemcitabine

Capecitabine

Cisplatin

Pancrelipase

Erlotinib Hydrochloride

Pancreatin

Antimetabolites

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dose-escalation phase I clinical study. In the initial dose levels, 'dose-escalation' refers to an increase in the radiotherapy dose delivered using carbon ion radiotherapy along with a corresponding decrease in the dose delivered using photons.

Study subjects will receive carbon ion radiotherapy (CIRT), with daily fraction sizes of 3 GyE. The total CIRT dose will increase with each dose level. Subjects in dose level 1 and 2 will receive photon radiotherapy as well.

Carbon Ion

Combined chemotherapy regimen before/after radiotherapy: gemcitabine-based chemotherapy regimen.

All patients will have received 2-4 cycles of gemcitabine-based chemotherapy prior to study registration, with post-chemotherapy imaging demonstrating locally-advanced disease without evidence of distant metastatic disease spread. Patients who received chemotherapy regimens other than those listed above may be considered for study enrollment at the discretion of the lead investigators, provided that all other eligibility criteria are satisfied. Gemcitabine-based chemotherapy will be continued starting 3-5 weeks after completion of radiotherapy until disease progression, intolerability, or the patient's decline of chemotherapy.

Gemcitabine + Cisplatin

Gemcitabine + Capecitabine

Gemcitabine + Erlotinib

During this study, the prescribed dose shall be administered according to the dose escalation shown in the table, starting with dose level 1. The carbon ion dose shall be gradually escalated while gradually reducing the dose of photons until eventually administering a full dose of 56 GyE/14 Fx carbon ions (fractional dose of 4 GyE). Dose escalation will be performed in parallel for two patient groups: patients whose pancreatic tumors are greater than 5 mm from the duodenum (Group A) and those whose tumors are within 5 mm of the duodenum (Group B). Enrolled patients will be monitored for 90 days after radiotherapy starts for any acute toxic reaction and to explore the maximum tolerated dose, in addition to being observed for any related long-term toxic reactions in accordance with the protocol.

Chandan Guha, M.B.B.S., Ph.D.

This is a phase I trial to determine the maximum tolerated dose of carbon ion radiotherapy for the treatment of locally advanced, unresectable, pancreatic cancer.

Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer

A Prospective Phase I Clinical Trial of Carbon Ion Radiation Therapy for Locally Advanced, Unresectable Pancreatic Cancer

Any CTCAE v. 4.03 non-hematologic adverse event of grade 3 or higher or any hematologic adverse event of grade 4 or higher, occurring within 90 days of the start of radiotherapy and deemed to be related to carbon ion radiotherapy.

Any grade 2 or higher treatment-related toxicity, scored using CTCAE v. 4.0

Radiographic changes following completion of study therapy (RECIST v. 1.1)

The length of time from study inclusion until death from any cause

The length of time from study inclusion until death from any cause or disease progression at any site

Quality of life will be assessed at various time points using the European Organisation for Research and Treatment of Cancer 30 items dealing with fatigue, pain, nausea and vomiting, general condition and social, emotional and cognitive functions. It is currently used in many cancer related clinical trials.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Heterogeneously Hypofractionated Radiotherapy for Locally Advanced NSCLC	NCT05548504	Non-small Cell ... Radiotherapy Si... Frailty	Photon Proton	18 Years -	Odense University Hospital
Heterogeneously Hypofractionated Radiotherapy for Locally Advanced NSCLC	NCT05548504	Non-small Cell ... Radiotherapy Si... Frailty	Photon Proton	18 Years -	Odense University Hospital
Proton Versus Photon Radiotherapy for Nasopharyngeal Carcinoma	NCT04528394	Nasopharyngeal ...	Photon Proton Carbon ion	18 Years - 70 Years	Shanghai Proton and Heavy Ion Center
Heterogeneously Hypofractionated Radiotherapy for Locally Advanced NSCLC	NCT05548504	Non-small Cell ... Radiotherapy Si... Frailty	Photon Proton	18 Years -	Odense University Hospital
Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer	NCT03403049	Pancreatic Canc... Cancer	Carbon Ion Gemcitabine + C... Gemcitabine + C... Gemcitabine + E... Gemcitabine Photon	18 Years - 99 Years	Albert Einstein College of Medicine
Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer	NCT03403049	Pancreatic Canc... Cancer	Carbon Ion Gemcitabine + C... Gemcitabine + C... Gemcitabine + E... Gemcitabine Photon	18 Years - 99 Years	Albert Einstein College of Medicine
Heterogeneously Hypofractionated Radiotherapy for Locally Advanced NSCLC	NCT05548504	Non-small Cell ... Radiotherapy Si... Frailty	Photon Proton	18 Years -	Odense University Hospital

Spots Global Cancer Trial Database for photon

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

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