Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Lung Neoplasms, Proton Therapy, Radiotherapy
Brief summary
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
RADIATIONDose-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).
DRUGCisplatin 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.
DRUGImmunotherapy: 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.
Sponsors
University Medical Center Groningen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Severe (grade 3+) adverse effects up to six months after radiotherapy | Data for assesing safety will be recorded from day 1 to 365 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local control of the lung tumour assessed by the treating physician and radiologist according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Data for assessing local control will be recorded up to 2 years after chemoradiotherapy | 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. |
| Progression-free survival based on review by the treating physician and radiologist according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Data for assessing progression-free survival will be recorded up to 2 years after chemoradiotherapy | 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. |
| Distant metastasis control based on review by the treating physician and radiologist according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Data for assessing distant metastasis will be recorded up to 2 years after chemoradiotherapy | 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. |
| 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) | Data for assesing quality of life will be recorded up to day 730 | 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. |
| European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13-item (EORTC-QLQ-LC13) | Data for assesing quality of life will be recorded up to day 730 | 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. |
| 3 EuroQoL-5D three-level version (EQ-5D-3L) | Data for assesing quality of life will be recorded up to day 730 | 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. |
| Lymphocyte counts after finishing chemoradiotherapy | Data for assessing lymphocyte counts will be assessed between 4 and 6 weeks after chemoradiotherapy | — |
Countries
Netherlands
Contacts
CONTACTA. Hessels, MD PhD
PRINCIPAL_INVESTIGATORR. Wijsman, MD PhD
University Medical Center Groningen
PRINCIPAL_INVESTIGATORA. Van der Wekken, MD PhD
University Medical Center Groningen
PRINCIPAL_INVESTIGATORE. Korevaar, dr ir (PhD)
University Medical Center Groningen
Outcome results
None listed