Alectinib Followed by Concomitant Consolidation Radiation Therapy in Advanced NSCLC With ALK-rearrangement (A-SAB)

Trial Title: Alectinib Followed by Concomitant Consolidation Radiation Therapy in Advanced NSCLC With ALK-rearrangement (A-SAB)

NCT ID: NCT05724004

Condition: Radiotherapy Side Effect
Non-small Cell Lung Cancer
ALK Gene Mutation

Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung

Conditions: Keywords:
Stereotactic body radiation therapy
SBRT
Radiotherapy
Non-small Cell Lung Cancer
ALK-rearrangement

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: Single arm, multicenter, phase I/II study

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: SBRT/SRS/radiation therapy
Description: Consolidation radiation therapy (SBRT/SRS/moderately hypofractionated radiation therapy)
Arm group label: Radiotherapy + alectinib

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 20 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Karolinska University Hospital

Address:
City: Stockholm
Zip: 171 76
Country: Sweden

Status: Recruiting

Contact:
Last name: Katja Tobin, PhD

Phone: +46851770000
Email: katja.tobin@regionstockholm.se

Investigator:
Last name: Karin Lindberg, MD, PhD
Email: Principal Investigator

Investigator:
Last name: Andreas Hallqvist, MD, PhD
Email: Principal Investigator

Start date: October 5, 2023

Completion date: June 20, 2031

Lead sponsor:
Agency: Karolinska University Hospital
Agency class: Other

Collaborator:
Agency: Sahlgrenska University Hospital, Sweden
Agency class: Other

Source: Karolinska University Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05724004