Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Anti-Infective Agents

All Drugs and Chemicals

Deoxyglucose

Chemo-radiotherapy with radiotherapy dose escalation based on Flour-Deoxy-Glucose /Positron Emissions Tomografi (FDG/PET) scans

Flour-Deoxy-Glucose /Positron Emissions Tomografi (FDG-PET) scans will be used to identify and delineate the tumour sub-volumes with the highest tracer uptake to guide the dose-escalation. The dose to the Gross tumor volume (GTV) will be escalated to a high dose while clinical target volume (CTV) and planning target volume (PTV) will be treated with standard dose.

Radiotherapy dose escalation

Hanna R Mortensen, MD PhD

In Denmark, 1000 new cases of esophageal and gastro-esophageal junction cancer occur every year. Surgery is the primary treatment for patients with localized disease who are considered medically and technically operable. For patients deemed non-resectable, definitive chemoradiotherapy is the treatment of choice, but despite treatment with curative intent, these patients have a poor prognosis, with a median survival of less than 20 months and a 5-year survival at 15-25% in clinical studies

This study will examine the effect of escalation of increasing the radiation dose to the most Positron Emissions Tomografi (PET) avid part of the tumour and lymph nodes compared to a standard uniform dose distribution.

In Denmark, there are almost 900 new cases of oesphageal and gastro-esophageal junction (GEJ) cancer per year, with a 5-year survival rate below 20% for the entire group and a 5-year survival rate of approximately 40% for the curatively treated patients.

Surgery is the primary treatment for patients with localized disease who are considered medically and technically operable. For patients deemed non-resectable, definitive chemoradiotherapy is the treatment of choice, but despite treatment with curative intent, these patients have a poor prognosis, with a median survival of less than 20 months and a 5-year survival at 15-25% in clinical studies.

Survival is affected by several factors like stage, gender and comorbidity, but also by lack of local and regional tumour control. Several studies examined pattern of failure in patients with oesophageal cancer treated with definitive chemoradiotherapy. Most patients experience local failure, and most local failures were located in the Gross Tumor volume (GTV). These findings imply that future therapeutic strategies should focus on improving local control in order to increase successful treatment outcome, although care should be taken to ensure that this does not come at the cost of excess treatment related toxicity.

Strategies to overcome in-GTV failures include radiotherapy-sensitizing agents and dose escalation, the latter has been evaluated in several studies with heterogeneous results.

The role of Positron Emissions Tomografi/ComputerTomografi (PET/CT) in radiotherapy planning has been examined and the diagnostic value of PET/CT in oesophageal cancer is widely accepted, whereas the role in assessing tumour response to treatment is less well established. Flour-Deoxy-Glucose (FDG)-PET scans allow for measurement of changes in tumour cell metabolism that precede changes in tumour size, and reduction in FDG uptake during neoadjuvant therapy has been correlated with favourable outcomes in patients with oesophageal cancer.

PET-positive areas have been suggested as suitable targets for dose-escalation strategies, since studies suggested that high FDG uptake on pre-treatment PET/CT identifies tumour sub-volumes that are at greater risk of recurrence after chemoradiotherapy in patients with locally advanced oesophageal cancer.

The major concern in a dose escalation study is severe and potentially lethal normal tissue complications. Oesophageal cancer irradiation usually results in irradiation of the oesophagus, lungs and heart due to the anatomical tumour location, which may result in acute toxicities dominated by radiation pneumonitis and esophagitis (leading to inappropriate nutricial intake). Late toxicities include oesophageal fistula/ulcers, cardiac events, pulmonary fibrosis, or even deaths related to radiation exposure. Dose gradients between the target and normal tissue may be sharp, in order to limit the norml tissue dose and hence the risk of unacceptable toxicity, while maintaining high doses to the tumour.

Current study Previous studies have suggested that escalating the radiation dose to the GTV may provide improved local control, but requires great caution in relation to normal tissue irradiation to avoid unacceptable side effects. The investigators propose a study approach where both requirements will be met. FDG-PET scans will be used to identify and delineate the tumour sub-volumes with the highest tracer uptake to guide the dose-escalation. The dose to the GTV will be escalated to a high dose (63Gray (Gy) in the FDG-PET avid areas in the primary tumour and 60 Gy in the lymph nodes) while Clinical target volume (CTV) and Planning target volume (PTV) will be treated with standard dose. The patients will be randomized between this dose-escalated arm and a standard arm with 50Gy in 25 fractions. The total number of fractions will be 25 in both arms. Dose escalation will be limited by normal tissues constraints.

The study will be conducted with modern state-of-the-art radiotherapy techniques, including advanced dose calculation algorithms, daily image guidance, and adaptation of the treatment plan during treatment if needed. The participating centres must implement and comply with a quality assurance program in order to maintain high treatment quality in the study.

Dose Escalated Adaptive RadioTherapy in Definitive Chemo-radiotherapy for Esophageal Cancer

Dose Escalated Adaptive RadioTherapy - a Randomised Phase II Study of Definitive Chemo-radiotherapy in Locally Advanced Esophageal Cancer

Loco-regional control evaluated with Flour-Deoxy-Glucose /Positron Emissions Tomografi (FDG-PET)

Acute and late toxicity during and after treatment and at follow-up visits

Time spent at hospital and number of hospitalizations due to radiation-induced toxicity

Mean and maximum doses for all organs at risk will be compared between proton therapy (in silico) and (clinical) IMRT/VMAT photon therapy.

V5, V10, V15, V20, V25, V30, V35, V40, V45 and V50 for all organs at risk will be compared between proton therapy (in silico) and (clinical) IMRT/VMAT photon therapy.

Number of Participants with failure in the Gross tumor volume-tumor (GTV-T)

Number of Participants with failure in the Gross tumor volume-nodes (GTV-N)

Number of Participants with failure in Gross tumor volume-PET avid (GTV-PET)

Number of Participants with failure in the clinical target volume (CTV)

Number of Participants with failure in the Planning target volume (PTV)

Number of Participants with failure in the outside the Planning target volume (PTV)

Changes in FDG-PET signal measured in terms of intensity

Changes in FDG-PET signal measured in terms of shape

Changes in FDG-PET signal measured in terms of heterogeniety

Response will be measured based on PERCIST and using radiomics characterizing the tumour in terms of uptake intensity, shape, and volumes.

Number of patients completing all radiotherapy treatments and receiving at least one cycle of chemotherapy

Aarhus University Hospital Skejby

Rigshospitalet, Denmark

Odense University Hospital

University of Aarhus

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Standard surgery plus intraoperative radiotherapy (20-30 Gy) followed by radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) and adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).

Standard surgery followed by radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) and adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).

Standard surgery

Dose to applicator surface: 20-30 Gy; Carl Zeiss INTRABEAM System. IORT with a surface dose of 30 Gy is recommended.Should the proximity to any risk structure not allow to apply 30 Gy, a dose reduction by up to 10 Gy (resulting in a surface dose of 20 Gy) is allowed.

Intraoperative radiotherapy

EBRT to 60 Gy plus 75 mg/m2/d temozolomide

Radiochemotherapy

Adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).

Martina Nesper-Brock, PhD

Clinical Trial Office UMM

Lisa Arnold

Norissa Honea, RN, PhD

Kris A. Smith, MD

Michael Lawton, MD

Beth A Chiappetta, RN, BSN, CCRP

Abhishek Solanki, MD

Louise A Purcell, MS ANP-C CCRN-CMC

Michael Schulder, MD

Tamika A Wong, MPH

John A. Boockvar, MD

Joseph Brunetti

Christopher P Cifarelli, MD, PhD, FAANS, FACS

Douglas Guedes de Castro, MD

Rodrigo Hanriot, MD

Kevin Petrecca, MD, PhD

Kevin Petrecca, MD

Luis Souhami, MD

Chengkai Zhang

Zhan Xue, MD

Sabine Schill, PhD

Klaus H Kahl, MD

Susanne Runewitz

Peter Vajkoczy, MD

Julia Onken, MD

Axel Madlung, MD

Oliver Sorge, MD

Anna Hedwig Müller

Studienzentrale Strahlentherapie

Michael Ehmann, MD

Nima Etminan, MD

Carmen Kessel, PhD

Stephanie E Combs, MD

Ulrike Arzbach

Oliver Ganslandt, MD

Marc Münter, MD

Mareike Schultes

Marc Piroth, MD

Ik Jae Lee, MD

Montserrat Ventura Bujalance

Ferran Guedea, MD, PhD

Sonia Garcia Cabezas, MD

Juan Solivera Vela, MD

Frank A. Giordano, MD

INTRAGO II resembles a multicentric, prospective, randomized, 2-arm, open-label clinical phase III trial which tests if the median progression-free survival (PFS) of patients with newly diagnosed glioblastoma multiforme (GBM) can be improved by the addition of intraoperative radiotherapy (IORT) to standard radiochemotherapy.

Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme

A Multicenter Randomized Phase III Trial on INTraoperative RAdiotherapy in Newly Diagnosed GliOblastoma Multiforme (INTRAGO II)

Determined according to modified Response Assessment in Neuro-Oncology (RANO) criteria and serial perfusion imaging

Determined by serial contrast-enhanced MRI scans using modified RANO criteria and serial perfusion imaging

Median overall survival of patients \<65 vs. ≥ 65 years

Progression-free survival of patients \<65 vs. ≥ 65 years; determined according to modified RANO criteria and serial perfusion imaging

Median overall survival of patients with KPS 80-100% vs. 60-70%

Progression-free survival of patients with KPS 80-100% vs. 60-70%; determined according to modified RANO criteria and serial perfusion imaging

Thickness of anticipated T1-Gd-enhancing (remaining) tumor margin as per the discretion of the surgeon (margin ≥0.5 cm or multiple spots of residual tumor within the cavity vs. \<0.5 cm)

Thickness of anticipated T1-Gd-enhancing (remaining) tumor margin as per the discretion of the surgeon (margin ≥0.5 cm or multiple spots of residual tumor within the cavity vs. \<0.5 cm); determined according to modified RANO criteria and serial perfusion imaging

Early postoperative MRI scans must be used to determine the extent of resection (EoR). The EoR is given as sum of all maximum diameters of residual lesions in cm. OS will be calculated for the following groups:

* Max Diameter group 0: 0 cm (no residual tumor)
* Max Diameter group 1: \>0 to ≤1.5 cm (cumulative if multiple residual lesions)
* Max Diameter group 2: \>1.5 cm (cumulative if multiple residual lesions)

Early postoperative MRI scans must be used to determine the extent of resection (EoR). The EoR is given as sum of all maximum diameters of residual lesions in cm. PFS will be determined according to modified RANO criteria and serial perfusion imaging for the following groups:

* Max Diameter group 0: 0 cm (no residual tumor)
* Max Diameter group 1: \>0 to ≤1.5 cm (cumulative if multiple residual lesions)
* Max Diameter group 2: \>1.5 cm (cumulative if multiple residual lesions)

OS in patients with promoter methylation vs. no promoter methylation

PFS in patients with promoter methylation vs. no promoter methylation; determined according to modified RANO criteria and serial perfusion imaging

Assessed by European Organization for Research and Treatment (EORTC)- Quality of Life Questionnaires (QLQ C30/BN20)

Change in functional outcomes as measured by BI from its baseline value.

Assessed by regular neurological examinations and serial MRI scans

Carl Zeiss Meditec AG

University of California, Los Angeles

Universitätsmedizin Mannheim

PI (Chair)

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Hypofractionated chest radiotherapy regimen of 58 Gy delivered in 25 fractions in 5 weeks.

Hypofractionated Chest Radiotherapy

It is accepted that giving higher doses of chest radiation in as short a time span as possible improves chances of cure. In this study, the investigators propose to give an increased dose of chest radiotherapy for limited stage small cell lung cancer patients using a strategy of giving a slightly higher daily dose of radiotherapy than normal. The investigators hypothesize that our proposed chest radiotherapy dose will improve 2-year overall survival rates in patients with limited stage small cell lung cancer.

The ideal chest radiotherapy dose/fractionation scheme for limited stage small cell lung cancer is undefined. Strategies of radiotherapy dose intensification with minimization of overall treatment time are felt to improve cure rates for LS-SCLC. Hypofractionation (giving higher than standard daily doses) facilitates both of these goals. In this study, we propose to use a dose escalated hypofractionated regimen of chest radiotherapy for patients with LS-SCLC.

Hypofractionated Radiotherapy for Limited Stage Small Cell Lung Cancer

A Clinical Trial of Increased Chest Radiotherapy Dose for Limited Stage Small Cell Lung Cancer

Cross Cancer Institute

AHS Cancer Control Alberta

hypofractionated external beam

Don Yee, MD

Current treatments for limited stage small cell lung cancer have poor cure rates. The addition of chest radiation to chemotherapy improves cure rates, but these cancers still come back in the chest 30-50% of the time. Two factors which can improve control and cure rates for this cancer are increasing the chest radiation dose and minimizing the overall time it takes to complete radiation treatments. One method to achieve both of these goals is to give more radiation each day. This study is meant to study how tolerable and effective it would be to increase the intensity of chest radiation for small cell lung cancer patients by increasing the daily radiation dose. We aim to find the highest dose of chest radiotherapy that can be safely given with chemotherapy using this strategy. Patients in this trial will be monitored before, during and after their radiation and chemotherapy treatments for treatment side-effects, how effective treatments are at controlling their cancer and quality of life changes. Results from this trial will help to define more effective radiotherapy doses which are tolerable for this type of lung cancer and the quality of life changes patients experience when they undergo these treatments.

Local control and overall survival rates associated with the standard chemotherapy and radiotherapy given for limited stage small cell lung cancer are poor and emerging evidence from several studies suggests that intensifying the radiotherapy dose given may further improve patient outcomes, but at the cost of increased radiotherapy side effects. This proposal aims to study a novel method of intensifying chest radiotherapy dose via increasing the daily radiotherapy dose which is directed at regions of visible disease only. This strategy allows for delivery of increased radiation doses without prolonging overall treatment time and allowing potential regrowth of cancer cells. We aim to determine the maximum radiation dose which can be safely given with chemotherapy for limited stage small cell lung cancer and study the effects this type of radiation regimen with chemotherapy has on patient side effects and quality of life. Results from this trial will contribute to the development of the ideal radiotherapy regimen for limited stage small cell lung cancer. Our results will add to the literature studying the effects dose-intense radiation strategies for lung cancer have on patient quality of life.

Hypofractionated Radiotherapy for Small Cell Lung Cancer

Phase I Dose Escalation Trial of Hypofractionated Limited-field External Beam Thoracic Radiotherapy for Limited Stage Small Cell Carcinoma of the Lung

Ear, Nose, and Throat Diseases

Carcinoma, Squamous Cell

Laryngeal Diseases

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Laryngeal Cancer

Increased dose of radiation therapy for locally advanced squamous cell carcinoma of the larynx or hypopharynx. Patients will also receive standard-of-care chemotherapy with the treatment regimen to be determined by the treating physicians.

Radiation Therapy

Standard-of-care chemotherapy with treatment regimen to be determined by the treating physician

Chemotherapy

Robert J Amdur, MD

This is a phase 2 single arm study of a novel schedule of hyperfractionated radiotherapy (RT) in combination with our standard chemotherapy program for patients with stage 3-4 squamous cell carcinoma of the larynx. The primary hypothesis of our study is that the study program will improve Laryngectomy-Free Survival compared to historical controls. The study is limited to patients who would be receiving primary RT-C as standard therapy off-study.

The novel radiotherapy schedule that is the subject of this study is only slightly different from the program that has been used in the cooperative group trial RTOG 9003. The radiation therapy dose schedule in our study twice-daily alternating fractions over 30 treatment days. The Biologically Effective Dose (BED) of this schedule is about 11% higher than our standard schedule twice-a-day. During radiotherapy, patients will receive chemotherapy with our standard program of weekly.

Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx

Patients will receive an increased dose of radiation therapy

The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients Likert scales 1-4,(1 = All, 2 = Little, 3 = a Bit, 4 = Very much)

Voice Handicap Index (VHI) a 30-item questionnaire. Likert scale 0- 4, 0 = never and 4 Always) A change between two administrations of 18 points represents a significant shift in psychosocial function.

The MD Anderson Symptom Inventory (MDASI) is a multi-symptom patient-reported outcome (PRO) measure for clinical and research use. Use the MDASI to assess the severity of symptoms experienced by patients with cancer and the interference with daily living caused by these symptoms.MD Anderson Dysphagia Index (MDADI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dose Escalated Adaptive RadioTherapy in Definitive Chemo-radiotherapy for Esophageal Cancer	NCT04086901	Esophageal Canc...	Radiotherapy do...	18 Years -	University of Aarhus
Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme	NCT02685605	Glioblastoma	Standard surger... Intraoperative ... Radiochemothera... Temozolomide	18 Years - 80 Years	Universitätsmedizin Mannheim
Hypofractionated Radiotherapy for Limited Stage Small Cell Lung Cancer	NCT00907569	Lung Neoplasm Small Cell Carc...	Hypofractionate...	18 Years -	AHS Cancer Control Alberta
Hypofractionated Radiotherapy for Small Cell Lung Cancer	NCT00469222	Lung Neoplasm Small Cell Carc...	hypofractionate...	18 Years -	AHS Cancer Control Alberta
Dose Escalated Adaptive RadioTherapy in Definitive Chemo-radiotherapy for Esophageal Cancer	NCT04086901	Esophageal Canc...	Radiotherapy do...	18 Years -	University of Aarhus
Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx	NCT03388931	Advanced Squamo...	Radiation Thera... Chemotherapy	18 Years -	University of Florida
Dose Escalated Adaptive RadioTherapy in Definitive Chemo-radiotherapy for Esophageal Cancer	NCT04086901	Esophageal Canc...	Radiotherapy do...	18 Years -	University of Aarhus
Hypofractionated Radiotherapy for Limited Stage Small Cell Lung Cancer	NCT00907569	Lung Neoplasm Small Cell Carc...	Hypofractionate...	18 Years -	AHS Cancer Control Alberta
Hypofractionated Radiotherapy for Small Cell Lung Cancer	NCT00469222	Lung Neoplasm Small Cell Carc...	hypofractionate...	18 Years -	AHS Cancer Control Alberta

Spots Global Cancer Trial Database for radiotherapy dose escalation