Clinical trial NCT05724004: Alectinib Followed by Concomitant Consolidation Radiation Therapy in Advanced NSCLC With ALK-rearrangement (A-SAB)
Official title: A-SAB - Alectinib Followed by Concomitant Consolidation SBRT/Hypofractionated Radiation Therapy/SRS in Advanced NSCLC With ALK-rearrangement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Radiotherapy Side Effect
Non-small Cell Lung Cancer
ALK Gene Mutation
Keywords: Stereotactic body radiation therapy
SBRT
Radiotherapy
Non-small Cell Lung Cancer
ALK-rearrangement
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Sahlgrenska University Hospital
First posted: 2023-02-13
Enrollment: 70
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm, multicenter, phase I/II study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Toxicity (safety)
timeFrame: 6 months post radiation therapy
measure: Progression free survival (PFS)
timeFrame: PFS rate at 12 months after initiation of alectinib
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
measure: Progression free survival II
timeFrame: 5 years
measure: Time to treatment failure
timeFrame: 3 years
measure: Time to next therapy
timeFrame: 5 years
Other outcomes:
measure: Translational biomarker studies
timeFrame: 5 years
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Karin Lindberg, MD, PhD
role: STUDY_DIRECTOR
References: