IMPT Dose Escalation for NSCLC (HyDose)

Official title

Radiotherapy Dose Escalation Using Intensity-modulated Proton Therapy for Non-small-cell Lung Cancer Patients

Overview

The goal of this clinical pilot trial is to learn if dose to the tumor in the lung can be safely increased using proton therapy in stage III non-small-cell lung cancer patients receiving combined chemotherapy and radiotherapy. The main questions it aims to answer are: * Is the risk of severe radiotherapy toxicities (requiring hospital admission) within acceptable margins ? * What is a rough estimate of the effect of the treatment under study? Compared to standard care in our clinic, all participants in this pilot trial will * Receive a higher dose of proton therapy to the tumor in the lung albeit with the same number of radiotherapy visits as the current standard treatment. * Receive two additional follow-up visits at the clinic after treatment, namely 4 and 6 weeks after finishing radiotherapy. * Two additional blood withdrawals at the last week of radiotherapy and 4 weeks after finishing radiotherapy, to measure a type of white blood cells. * Receive an extra quality of life questionnaire at the last week of radiotherapy.

Interventions

• Radiation Dose-escalated intensity-modulated proton therapy (IMPT-74)
  Heterogeneous simultaneous integrated boost of 74.0 Gy (RBE) to primary tumor \>15mm away form mediastinal envelope, and 64.0 Gy (RBE) to primary tumor =\< 15mm away from mediastinal envelope. The rest of the clinical target volume, including affected lymph nodes, receives 60.0 Gy (RBE).
• Drug Cisplatin or carboplatin + pemetrexed for induction chemotherapy, cisplatin + docetaxel for concurrent chemotherapy
  Induction course: -Cisplatin (75 mg/m2) or carboplatin (AUC 6) + pemetrexed (500mg/m2). Concurrent chemoradiotherapy: * Weekly cisplatin (20mg/m2) + docetaxel (20mg/m2) on Mondays. * Radiotherapy will be given for 5x5 days.
• Drug Immunotherapy: adjuvant durvalumab
  Adjuvant treatment will be given starting 1-6 weeks after chemoradiotherapy if no progression, good performance (PS 0-1), no other contra-indication for immunotherapy. Doses: * Start durvalumab 10 mg/kg 1x/14 days. * If possible after 2 courses switch to 1500 mg flat dose 1x/4 wk. * Continue for 12 months in total.

Primary outcome measures

• Severe (grade 3+) adverse effects up to six months after radiotherapy [Time frame: Data for assesing safety will be recorded from day 1 to 365]

Secondary outcome measures (10)

• Local control of the lung tumour assessed by the treating physician and radiologist according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [Time frame: 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) [Time frame: 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 frame: Data for assessing distant metastasis will be recorded up to 2 years after chemoradiotherapy]
• Overall survival [Time frame: 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 [Time frame: Data for assesing safety will be recorded from day 1 to 365]
• Qualifying for adjuvant immunotherapy after finishing chemoradiotherapy yes/no [Time frame: 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) [Time frame: 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) [Time frame: Data for assesing quality of life will be recorded up to day 730]
• 3 EuroQoL-5D three-level version (EQ-5D-3L) [Time frame: Data for assesing quality of life will be recorded up to day 730]
• Lymphocyte counts after finishing chemoradiotherapy [Time frame: Data for assessing lymphocyte counts will be assessed between 4 and 6 weeks after chemoradiotherapy]

Eligibility criteria

Inclusion criteria

• Age ≥18 years
• WHO performance score 0-2
• Histologically proven stage III NSCLC
• Planned for CCRT and adjuvant immunotherapy (intention to treat)
• Primary tumour volume outside of mediastinal PRV (i.e., mediastinal envelope + 5 mm) ≥60% of total primary tumour volume (true for 75% of patients in preliminary analysis), for sufficient dose escalation

Exclusion criteria

• Chemotherapy not given concurrently with radiotherapy
• Upfront decision that adjuvant immunotherapy is not possible
• Primary tumour overlapping ≥40% with mediastinal PRV
• Unable or unwilling to understand the information on trial-related topics, to give informed consent or to fill out quality-of-life questionnaires

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• UMCG — Groningen

Identifiers

NCT: NCT06484491 · PNM16745 · NL86435.042.24

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗