ALK Gene Mutation, Non-small Cell Lung Cancer, Radiotherapy Side Effect
Conditions
Keywords
Stereotactic body radiation therapy, SBRT, Radiotherapy, Non-small Cell Lung Cancer, ALK-rearrangement
Brief summary
The goal of this clinical trial is to learn evaluate the safety and efficacy of the addition of radiation therapy to all tumour lesions, to first line medical treatment with alectinib in non-small cell lung cancer harbouring ALK-rearrangements. The main aims of the trial are to evaluate: * if the treatment combination is safe * if the treatment combination can inhibit progression Participants who have responded to 1st line alectinib will be treated with consolidation radiation therapy to all remaining tumour lesions while continuing on alectinib until disease progression, unacceptable toxicity or another discontinuation criterion is met.
Detailed description
This is phase I/II study to evaluate the feasibility (phase I) and progression free survival (phase II) in patients with advanced NSCLC with ALK-rearrangement receiving consolidation radiation therapy (RT) to all known macroscopic tumour lesions present after 2-3 months of treatment with alectinib and then continuing with alectinib. Eligible patients are those with an ALK-rearranged stage III (non-surgical/non-radiochemotherapy candidates) OR stage IV NSCLC who, after a 2-3-month-induction period of alectinib show stable disease/partial response to systemic therapy. When entering the trial, all known tumour lesions are treated with SBRT/RT/SRS with concomitant alectinib followed by continuation alectinib until disease progression, unacceptable toxicity or another discontinuation criterion is met.
Interventions
RADIATIONSBRT/SRS/radiation therapy
Consolidation radiation therapy (SBRT/SRS/moderately hypofractionated radiation therapy)
Sponsors
Sahlgrenska University Hospital
Karolinska University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm, multicenter, phase I/II study
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histological or cytological confirmed NSCLC: * Stage IV NSCLC OR * Stage III NSCLC not suitable for surgery or radiochemotherapy OR * Recurrent NSCLC after previous surgery (not amendable for curative multimodal therapy) 2. ALK-rearrangement 3. Adequate organ function to tolerate alectinib and clinical tolerance to alectinib 4. Stable disease (SD) or partial response (PR) after 2-3 months induction treatment with alectinib 5. Maximum 5 tumour lesions +/- thoracic lymph nodes active on an 18F-FDG-PET scan post induction treatment with alectinib 6. All active tumour lesions amendable to RT under the following conditions: * All metastases possible to treat with * Extracranial metastases: SBRT of at least 7 Gy x 5 (corresponding to 50 Gy EQD2 using alfa/beta 10Gy) * Intracranial metastases: SRS or f-SRS * The primary tumour and/or lymph nodes and/or pulmonary metastases amendable to SBRT (≥ 7Gy x 5, see above) or moderately hypofractionated RT of 3 Gy x 15 (corresponding to 49 Gy EQD2 using alfa/beta 10Gy) 7. Adequate organ function to tolerate SBRT/RT: * Fulfilment of dose constraints to adequate organs at risk 8. ECOG performance status (PS) 0-2 9. FEV1 ≥1 litre (only applicable for lung targets) 10. Age ≥ 20 years 11. Measurable lesions according to RECIST v 1.1 12. Signed written informed consent
Exclusion criteria
1. Leptomeningeal carcinosis (on MRI or in cerebrospinal fluid (CSF)) 2. Persistent malignant pleural effusion, malignant pericardial effusion or malignant ascites after induction treatment 3. PD after 2-3-month-induction treatment with alectinib 4. Previous TKI, chemotherapy or immunotherapy (previous adjuvant chemotherapy for early stage NSCLC is allowed) for metastatic NSCLC 5. Previous RT for NSCLC (any stage) 6. Previous RT for any other cancer within the last 3 years possibly interfering with the planned RT within this study 7. Life expectancy of less than 6 months 8. Inability to understand given information or undergo study procedures according to protocol. 9. Has evidence or a past medical history of interstitial lung disease or active, non-infectious pneumonitis or known pulmonary fibrosis. 10. Pregnant or breast-feeding. Patients must agree to use safe contraception during and for 3 months after study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | PFS rate at 12 months after initiation of alectinib | PFS-rate at 12 months (KM-estimated method). Successrate is 12-month-PFS-rate of 85%. Median PFS will also be measured |
| Toxicity (safety) | 6 months post radiation therapy | No and percentage of patients suffering grade 3-5 toxicity attributed to RT and within 6 months post RT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to treatment failure | 3 years | Time between the date of initiation of alectinib and the date of documented progressive disease, unacceptable toxicity related to SBRT, toxicity attributed to alectinib leading to interruption of the treatment or death. (Time between the date of initiation of alectinib and the date of documented 2nd tumour progression or death, from whatever reason.) TTF-rate at 1-, 2-, 3- and 5 years (KM-method). |
| Progression free survival II | 5 years | (Time between the date of initiation of alectinib and the date of documented 2nd tumour progression or death, from whatever reason.) PFS II rate at 1-, 2-, 3- and 5 years (KM-method) will be measured. |
| Overall survival | 5 years | OS-rate at 1-, 2-, 3- and 5 years post initiation of alectinib using the KM-method. Median OS will also be measured. |
| Time to next therapy | 5 years | Time between the date of initiation of alectinib and the date of next therapy. (Time between the date of initiation of alectinib and the date of documented 2nd tumour progression or death, from whatever reason.) Rate at 1-, 2-, 3- and 5 years (KM-method). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Translational biomarker studies | 5 years | For plasma samples: extracellular vesicles isolated from plasma are profiled for protein and RNA expression with linkage to clinical response and tumor marker expression. |
Countries
Sweden
Contacts
Primary ContactKarin Lindberg, MD, PhD
Outcome results
None listed