Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Head and Neck Neoplasms

Xerostomia

Oropharyngeal Neoplasms

Salivary Gland Diseases

Mouth Diseases

Stomatognathic Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Standard radiotherapy planning aims to restrict the mean parotid radiation dose to less than or equal to 14 Gy.

Magnetic resonance images will be used to localize the parotid ducts and limit the radiation dose to these structures to less than or equal to 14 Gy.

radiotherapy planning goal is to restrict the mean parotid dose is equal to or less than 14Gy.

standard radiotherapy

radiotherapy planning goal is to restrict the parotid duct dose is equal to or less than 14Gy

experimental radiotherapy

Melissa Knutsen, MPH

Tuvara King

Colette Shen, MD

Radiation-induced xerostomia (dry mouth) is one of the most common and severe toxicities experienced by patients undergoing radiation treatment for head and neck cancer. Radiation-induced dry mouth is a frequently experienced symptom and persists after treatment, potentially indefinitely. Current practice does not specifically attempt to spare the parotid ducts, where stem/progenitor cells are believed to preferentially reside, and considers the entire salivary gland to have equal function. New radiation therapy planning and conducting strategies are needed to reduce this toxicity and maximize patient quality of life post-treatment.

This randomized Phase II study explores the contribution of magnetic resonance imaging (MRI) guided salivary gland duct definition to decrease patient-reported xerostomia in patients with oropharynx cancer receiving radiation therapy. The severity of xerostomia will be measured by patient-reported (PRO) symptoms, saliva secretion, saliva pH, and buffering.

Sparing Parotid Ducts Via MRI Sialography for Reduced Patient Reported Xerostomia

Randomized Assessment of Sparing Parotid Ducts Via MRI Sialography for Reduced Patient-Reported Xerostomia Following Radiotherapy for Oropharynx Cancer

The difference in patient-reported xerostomia will be assessed using the MD Anderson Symptom Inventory -Head \& Neck (MDASI-HN) questionnaire. MDASI multi-symptom patient-reported outcome (PRO) measure for clinical and research use. Use the MDASI to assess the severity of symptoms Each question is scaled from 0 to 10. 0= not present and 10= as bad as you imagine.

The mass of generated saliva post-radiation treatment will be measured.

The efficacy of 14Gy parotid duct constraint for subjects undergoing parotid ductal sparing radiation therapy will be measured using patient-reported xerostomia scores.

The difference in patient-reported xerostomia will be assessed using the MD Anderson Symptom Inventory -Head \& Neck (MDASI-HN) questionnaire. MDASI multi-symptom patient-reported outcome (PRO) measure for clinical and research use. Each question is scaled from 0 to 10. 0= not present and 10= as bad as you imagine.

xerostomia will be assessed using The National Cancer Institute Common Terminology Criteria for Adverse Events is a descriptive terminology (NCI-CTCAE) v5.0 that can be utilized for Adverse Event (AE) reporting.

A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

UNC Lineberger Comprehensive Cancer Center

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Immunologic Factors

standard FDG-PET-based radiotherapy with concurrent standard of care chemotherapy

FDG-PET-based small volume accelerated radiotherapy with concurrent standard of care chemotherapy

standard Radiotherapy

Chemotherapy

standard of care consolidation therapy with durvalumab (fixed dose of 1500 mg q4w) for up to 12 months or until progression of disease, unacceptable toxicity, patient´s wish, or investigator´s decision, whichever comes first.

Immunotherapy

FDG-PET-based small volume accelerated radiotherapy

Experimental Radiotherapy

Ursula Nestle, Prof.

Stefan Rieken, Prof.

Multinational, randomized, controlled, open-label, multicenter phase II trial. Eligible patients will be randomized in a ratio of 1:1 to Experimental Arm (FDG-PET-based small volume accelerated radiotherapy with concurrent standard of care chemotherapy) or Conventional Arm (standard FDG-PET-based radiotherapy with concurrent standard of care chemotherapy). Patients showing complete response, partial response, or stable disease following chemoradiotherapy will receive standard of care consolidation therapy with durvalumab (fixed dose of 1500 mg q4w) for up to 12 months or until progression of disease, unacceptable toxicity, patient´s wish, or investigator´s decision, whichever comes first.

After end of durvalumab therapy, patients will undergo safety follow up for 90 (+7) days followed by survival follow up until overall end of study. Overall end of study will be reached 24 months after the last patient has started durvalumab therapy. Patients showing PD following chemoradiotherapy will be treated according to investigator´s decision but will be followed up until overall end of study.

Experimental Arm (FDG-PET-based small volume accelerated radiotherapy with concurrent standard of care chemotherapy) Conventional Arm (standard FDG-PET-based radiotherapy with concurrent standard of care chemotherapy)

PACCELIO - FDG-PET Based Small Volume Accelerated Immuno Chemoradiotherapy in Locally Advanced NSCLC

Quantifiable imaging parameters (e.g., SUV) will be correlated to response and survival outcomes, reflected in separate protocol to be setup

SUV is a common unitless measurement for radioactivity uptake. In the study we will measure maximum SUV and mean SUV from tumor volume. The tumor volume with the unit millilitre will be measured by an automatic segmentation were any area with SUV above a threshold value of 40% of SUVmax will be attributed to the tumor volume. These imaging parameters will be correlated with time to progression from randomization

Quantifiable imaging parameters (e.g., SUV) will be correlated to response and survival outcomes, reflected in separate protocol to be setup

SUV is a common unitless measurement for radioactivity uptake. In the study we will measure maximum SUV and mean SUV from tumor volume. The tumor volume with the unit millilitre will be measured by an automatic segmentation were any area with SUV above a threshold value of 40% of SUVmax will be attributed to the tumor volume. These parameters will be correlated with time to progression from randomization Also, for changes of measurements of SUVmax and SUVmax from baseline correlation will be done with time to progression. In this analyisis also changes in tumor diameter (measured from CT) and changes in tumor volume (measured from PET) will be included into the analysis.

Quantifiable imaging parameters (e.g., SUV) will be correlated to response and survival outcomes, reflected in separate protocol to be setup

SUV is a common unitless measurement for radioactivity uptake. In the study we will measure maximum SUV and mean SUV from tumor volume. The tumor volume with the unit millilitre will be measured by an automatic segmentation were any area with SUV above a threshold value of 40% of SUVmax will be attributed to the tumor volume. These imaging parameters will be correlated with time to progression from randomization Further changes of measurements of SUVmax, SUVmax, tumor diameter and tumor volume from end of chemoradiation therapy will be correlated with time to progression in the subgroup receiving three PET/CT scans.

Relation of NLR to response and survival outcomes, reflected in separate protocol to be setup

It is calculated by dividing the number of neutrophils by number of lymphocytes.

Relation of ALI Index (Advance lung cancer inflammation) to response and survival outcomes, reflected in separate protocol to be setup

ALI is calculated as (BMI x Alb / NLR) where BMI = body mass index, Alb = serum albumin, NLR (neutrophil lymphocyte ratio, a marker of systemic inflammation).

Relation of EDIC to immunomarkers (NLR), reflected in separate protocol to be setup

The EDIC model considers the exposure of circulating immune cells as the proportion of blood flow to lung, heart, liver, and the volume of the exposed area of the body, with the basis of mean lung dose, mean heart dose, mean liver dose and integral dose of the body region which are to be extracted from the RT plan. EDIC will be calculated as described in Xu et al. 2020.

NLR is calculated by dividing the number of neutrophils by number of lymphocytes.

Relation of EDIC to immunomarkers (ALI), reflected in separate protocol to be setup

The EDIC model considers the exposure of circulating immune cells as the proportion of blood flow to lung, heart, liver, and the volume of the exposed area of the body, with the basis of mean lung dose, mean heart dose, mean liver dose and integral dose of the body region which are to be extracted from the RT plan. EDIC will be calculated as described in Xu et al. 2020.

ALI is calculated as (BMI x Alb / NLR) where BMI = body mass index, Alb = serum albumin, NLR (neutrophil lymphocyte ratio, a marker of systemic inflammation).

Relation of EDIC to response to chemoradio-immunotherapy, reflected in separate protocol to be setup

The EDIC model considers the exposure of circulating immune cells as the proportion of blood flow to lung, heart, liver, and the volume of the exposed area of the body, with the basis of mean lung dose, mean heart dose, mean liver dose and integral dose of the body region which are to be extracted from the RT plan. EDIC will be calculated as described in Xu et al. 2020.

Relation of EDIC to survival outcomes, reflected in separate protocol to be setup

The EDIC model considers the exposure of circulating immune cells as the proportion of blood flow to lung, heart, liver, and the volume of the exposed area of the body, with the basis of mean lung dose, mean heart dose, mean liver dose and integral dose of the body region which are to be extracted from the RT plan. EDIC will be calculated as described in Xu et al. 2020.

To assess the feasibility of an FDG-PET-based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab compared to standard FDG-PET-based chemoradiotherapy followed by immunotherapy with durvalumab Completion rate defined as rate of patients having received:

* the prescribed radiotherapy dose ± 2 fractions and
* simultaneous platinum-based chemotherapy and · immunotherapy consolidation with durvalumab starting within 42 days after the last dose of chemoradiotherapy and
* either at least 3 doses of durvalumab or less than 3 doses of durvalumab in case immunotherapy was permanently discontinued due to documented extrathoracic immune-related toxicity.

To assess the safety and tolerability of an FDGPET- based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab compared to standard FDG-PET-based chemoradiotherapy followed by immunotherapy with durvalumab

Occurrence of adverse events and serious events:

* adverse events grade ≥ 3 (according to NCI CTCAE v5.0)
* SAEs
* Unexpected AEs

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress

- Time to locoregional progression

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress

· Time to locoregional in-RT-field progression

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress

· Time to locoregional out-of-RT-field progression

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress

· Time to distant progression time from rando to appearance of metastases elsewhere

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress

· PFS

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress

· OS

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress

· ORR

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress

· DCR

Assess symptoms and patient-reported QoL in patients receiving an FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to patients receiving standard FDG-PET-based CRT followed by immunotherapy

1. Change in symptoms assessed with the EORTC QLQ-C30
2. Change in symptoms assessed with the EORTC QLQ-LC13

The results of the questionnaire are usually presented as scale scores, ranging from 0 to 100. Higher scores on the symptom scales indicate a worse quality of life.

Assess symptoms and patient-reported QoL in patients receiving an FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to patients receiving standard FDG-PET-based CRT followed by immunotherapy

1. Change in functioning assessed with the EORTC QLQ-C30
2. Change in functioning assessed with the EORTC QLQ-LC13

The results of the questionnaire are usually presented as scale scores, ranging from 0 to 100. Higher scores on the functional scales indicate a better quality of life.

Assess symptoms and patient-reported QoL in patients receiving an FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to patients receiving standard FDG-PET-based CRT followed by immunotherapy

1. Change in global health-status/QoL assessed with the EORTC QLQ-C30
2. Change in global health-status/QoL assessed with the EORTC QLQ-LC13

The results of the questionnaire are usually presented as scale scores, ranging from 0 to 100. Higher scores on the global health and quality of life scale indicate a better quality of life.

Percentage of patients without major protocol deviations regarding radiotherapy quality

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sparing Parotid Ducts Via MRI Sialography for Reduced Patient Reported Xerostomia	NCT06276946	Oropharynx Canc... Head and Neck C... Xerostomia	standard radiot... experimental ra...	18 Years -	UNC Lineberger Comprehensive Cancer Center
PACCELIO - FDG-PET Based Small Volume Accelerated Immuno Chemoradiotherapy in Locally Advanced NSCLC	NCT06102057	Stage III Non-s... Locally Advance... Unresectable	standard Radiot... Chemotherapy Immunotherapy Experimental Ra...	18 Years -	TheraOp

Spots Global Cancer Trial Database for experimental radiotherapy