IMPT Dose Escalation for NSCLC (HyDose)
NCT Number: NCT06484491
Acronym: HyDose
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Carcinoma, Non-Small-Cell Lung
Interventions: RADIATION: Standard-dose intensity-modulated proton therapy (IMPT-60)|RADIATION: Dose-escalated intensity-modulated proton therapy (IMPT-74)|DRUG: Cisplatin or carboplatin + pemetrexed for induction chemotherapy, cisplatin + docetaxel for concurrent chemotherapy|DRUG: Immunotherapy: adjuvant durvalumab
Sponsor: University Medical Center Groningen
Collaborators: Dutch Cancer Society
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 110
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-01
Completion Date: 2027-01-01
Locations: UMCG, Groningen, Netherlands

Summary:
In this randomized controlled trial, the aim is to test the hypothesis that proton therapy dose escalation using a heterogeneous simultaneous boost on the primary tumor as part of chemoradiotherapy for locally advanced non-small-cell lung cancer is safe, i.e. does not result in an increase in severe toxicity compared to standard-dose proton therapy. Secondarily, the goal is to estimate the treatment effect size, if any.

In the intervention group, patients will receive intensity-modulated proton therapy dose escalation to the primary tumor up to 74.0 Gy or 64.0 Gy (RBE of 1.1) in 25 fractions, depending on proximity to the mediastinal envelope. In the control group, patients will receive 60.0 Gy intensity-modulated proton therapy in 25 fractions.

Primary Outcome Measures: Severe (grade 3+) adverse effects in the first year after radiotherapy, Data for assesing safety will be recorded from day 1 to 365
Secondary Outcome Measures: Local control of the lung tumour assessed by the treating physician and radiologist according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), Local control was defined as the time from randomization until the date of objective disease progression in the lungs (RECIST 1.1). Local progression was defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Local control was calculated using the Kaplan-Meier technique., Data for assessing local control will be recorded up to 2 years after chemoradiotherapy|Progression-free survival based on review by the treating physician and radiologist according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), PFS was defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). Progression was defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PFS was calculated using the Kaplan-Meier technique., Data for assessing progression-free survival will be recorded up to 2 years after chemoradiotherapy|Distant metastasis control based on review by the treating physician and radiologist according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), Time to distant metastasis was defined as the time from the date of randomization until the first date of distant metastasis. Distant metastasis was defined as any new lesion that was outside of the radiation field according to RECIST 1.1 or proven by biopsy. Time to distant metastasis was calculated using the Kaplan-Meier technique., Data for assessing distant metastasis will be recorded up to 2 years after chemoradiotherapy|Overall survival, Data for assessing overall survival will be recorded up to 2 years after chemoradiotherapy|Grade 2+ adverse effects (i.e., requiring medication), both acute and late, Data for assesing safety will be recorded from day 1 to 365|Qualifying for adjuvant immunotherapy after finishing chemoradiotherapy yes/no, Data on qualifying for adjuvant immunotherapy will be recorded up to 6 weeks after finishing chemoradiotherapy|European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core-30 item (EORTC QLQ-C30), The EORTC QLQ-C30 is a disease specific measurement instrument for use in patients with or cured from cancer. It measures a number of aspects of quality of life, namely: physical functioning; role functioning; emotional functioning; cognitive functioning; social functioning. It also evaluates symptoms, such as pain, nausea, sleep, dyspnea, cancer related fatigue, and constipation, diahorrea, and fincancial problems, as well as two questionas about overall quality of life.

The questionnaire consists of a total of 30 items, divided over 9 subscales. The items are on Likert scales. The scores for each subscale can be calculated on a 0-100 scale, as well as the total score. A high score for a functional scale represents a high/healthy level of functioning. A high score for global health status / QoL represents a high QoL. By contrast, a high score for a symptom scale/item represents a high level of symptomatology/problems., Data for assesing quality of life will be recorded up to day 730|European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13-item (EORTC-QLQ-LC13), The EORTC QLQ-LC13 is a 13-item lung cancer-specific questionnaire module meant as a disease-specific extension to the EORTC QLC-C30. It contains both multi-item (dyspnea) and single-item (all others) measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). The items are scored on likert scales, and can be converted to a 0-100 scale for each symptom and side effect. A high score represents a high level of symptomatology or problems., Data for assesing quality of life will be recorded up to day 730|3 EuroQoL-5D three-level version (EQ-5D-3L), This questionnaire consists of two pages: the EQ-5D descriptive system and the EQ-5D visual analogue scale (EQ VAS):

* The descriptive system comprises five dimensions, each describing a different aspect of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has three levels: no problems, some problems, extreme problems (labelled 1-3). The respondent indicates their health by checking the box against the most appropriate statement in each of the five dimensions.
* The EQ VAS redords the respondent's self-rated health on a vertical VAS where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. This information can be used as a quantitative measure of health outcome as judged by the individual respondents., Data for assesing quality of life will be recorded up to day 730|Lymphocyte counts after finishing chemoradiotherapy, Data for assessing lymphocyte counts will be assessed between 4 and 6 weeks after chemoradiotherapy