Combining Alectinib with Radiation Therapy for Advanced Lung Cancer with ALK Mutation

A-SAB - Alectinib Followed by Concomitant Consolidation SBRT/Hypofractionated Radiation Therapy/SRS in Advanced NSCLC With ALK-rearrangement

This study is testing if combining alectinib with targeted radiation therapy can help people with advanced lung cancer that has an ALK mutation feel better and live longer.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: Karolinska University Hospital (other)
• Drugs / interventions: alectinib, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Stockholm)
• Trial ID: NCT05724004 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of adding radiation therapy to alectinib treatment in patients with advanced non-small cell lung cancer (NSCLC) that has ALK-rearrangements. Participants who have shown a stable disease or partial response after 2-3 months of alectinib will receive stereotactic body radiation therapy (SBRT) to all remaining tumor lesions while continuing alectinib. The study aims to assess both the feasibility of this combination treatment and its impact on progression-free survival. The trial is designed for patients who are not candidates for surgery or traditional radiochemotherapy.

Who should consider this trial

Good fit: Ideal candidates include patients with stage III or IV NSCLC harboring ALK-rearrangements who have shown stable disease or partial response after initial alectinib treatment.

Not a fit: Patients with early-stage NSCLC or those who have not responded to alectinib may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and prolong survival for patients with advanced ALK-rearranged NSCLC.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies and radiation, indicating potential for success in this approach.

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.

Where this trial is running

Stockholm

• Karolinska University Hospital — Stockholm, Sweden (RECRUITING)

Study contacts

• Study coordinator: Karin Lindberg, MD, PhD

Conditions: Radiotherapy Side Effect, Non-small Cell Lung Cancer, ALK Gene Mutation, Stereotactic body radiation therapy, SBRT, Radiotherapy, ALK-rearrangement