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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; ALK Gene Mutation; Radiotherapy Side Effect
• Intervention / Treatment: Radiation: SBRT/SRS/radiation therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karin Lindberg, MD, PhD; Phone Number: +46851770000; Email: karin.lindberg@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden, 171 76
    • Recruiting
    • Karolinska University Hospital
    • Contact: Katja Tobin, PhD; Phone Number: +46851770000; Email: katja.tobin@regionstockholm.se
    • Principal Investigator: Karin Lindberg, MD, PhD
    • Principal Investigator: Andreas Hallqvist, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy + alectinib; All patients receive consolidation radiation therapy to all active tumour lesions after induction treatment with alectinib.	Radiation: SBRT/SRS/radiation therapy; Consolidation radiation therapy (SBRT/SRS/moderately hypofractionated radiation therapy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity (safety)	No and percentage of patients suffering grade 3-5 toxicity attributed to RT and within 6 months post RT).	6 months post radiation therapy
Progression free survival (PFS)	PFS-rate at 12 months (KM-estimated method). Successrate is 12-month-PFS-rate of 85%. Median PFS will also be measured	PFS rate at 12 months after initiation of alectinib

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS-rate at 1-, 2-, 3- and 5 years post initiation of alectinib using the KM-method. Median OS will also be measured.	5 years
Progression free survival II	(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.	5 years
Time to treatment failure	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).	3 years
Time to next therapy	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).	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Translational biomarker studies	For plasma samples: extracellular vesicles isolated from plasma are profiled for protein and RNA expression with linkage to clinical response and tumor marker expression.	5 years

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Sahlgrenska University Hospital, Sweden
• Investigators: Study Director: Karin Lindberg, MD, PhD, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2023
• Primary Completion (Estimated): June 20, 2024
• Study Completion (Estimated): June 20, 2031

Study Registration Dates

• First Submitted: January 20, 2023
• First Submitted That Met QC Criteria: February 1, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Radiotherapy; SBRT; Non-small Cell Lung Cancer; Stereotactic body radiation therapy; ALK-rearrangement
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: A-SAB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No