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

NCT ID: NCT05724004

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-05
• Study Completion Date: 2031-06-20

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiotherapy + alectinib

All patients receive consolidation radiation therapy to all active tumour lesions after induction treatment with alectinib.

Group Type: EXPERIMENTAL

SBRT/SRS/radiation therapy

Intervention Type: RADIATION

Consolidation radiation therapy (SBRT/SRS/moderately hypofractionated radiation therapy)

Interventions

SBRT/SRS/radiation therapy

Consolidation radiation therapy (SBRT/SRS/moderately hypofractionated radiation therapy)

Intervention Type: RADIATION

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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sahlgrenska University Hospital

OTHER

Sponsor Role: collaborator

Karolinska University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Karin Lindberg

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karin Lindberg, MD, PhD

Role: STUDY_DIRECTOR

Karolinska University Hospital

Locations

Karolinska University Hospital

Stockholm, , Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Karin Lindberg, MD, PhD

Role: CONTACT

karin.lindberg@ki.se

+46851770000

Facility Contacts

Katja Tobin, PhD

Role: primary

katja.tobin@regionstockholm.se

+46851770000

Other Identifiers

A-SAB

Identifier Type: -

Identifier Source: org_study_id