Back to resultsAlectinib Followed by Concomitant Consolidation Radiation Therapy in Advanced NSCLC With ALK-rearrangement (A-SAB) (A-SAB)
Primary Purpose
Radiotherapy Side Effect, Non-small Cell Lung Cancer, ALK Gene Mutation
Status
Recruiting
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
SBRT/SRS/radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Radiotherapy Side Effect focused on measuring Stereotactic body radiation therapy, SBRT, Radiotherapy, Non-small Cell Lung Cancer, ALK-rearrangement
Eligibility Criteria
Inclusion Criteria: 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) ALK-rearrangement Adequate organ function to tolerate alectinib and clinical tolerance to alectinib Stable disease (SD) or partial response (PR) after 2-3 months induction treatment with alectinib Maximum 5 tumour lesions +/- thoracic lymph nodes active on an 18F-FDG-PET scan post induction treatment with alectinib 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) Adequate organ function to tolerate SBRT/RT: Fulfilment of dose constraints to adequate organs at risk ECOG performance status (PS) 0-2 FEV1 ≥1 litre (only applicable for lung targets) Age ≥ 20 years Measurable lesions according to RECIST v 1.1 Signed written informed consent Exclusion Criteria: Leptomeningeal carcinosis (on MRI or in cerebrospinal fluid (CSF)) Persistent malignant pleural effusion, malignant pericardial effusion or malignant ascites after induction treatment PD after 2-3-month-induction treatment with alectinib Previous TKI, chemotherapy or immunotherapy (previous adjuvant chemotherapy for early stage NSCLC is allowed) for metastatic NSCLC Previous RT for NSCLC (any stage) Previous RT for any other cancer within the last 3 years possibly interfering with the planned RT within this study Life expectancy of less than 6 months Inability to understand given information or undergo study procedures according to protocol. Has evidence or a past medical history of interstitial lung disease or active, non-infectious pneumonitis or known pulmonary fibrosis. Pregnant or breast-feeding. Patients must agree to use safe contraception during and for 3 months after study treatment.
Sites / Locations
- Karolinska University HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Radiotherapy + alectinib
Arm Description
All patients receive consolidation radiation therapy to all active tumour lesions after induction treatment with alectinib.
Outcomes
Primary Outcome Measures
Toxicity (safety)
No and percentage of patients suffering grade 3-5 toxicity attributed to RT and within 6 months post RT).
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
Secondary Outcome Measures
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.
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.
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).
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).
Full Information
NCT ID
NCT05724004
First Posted
January 20, 2023
Last Updated
October 6, 2023
Sponsor
Karolinska University Hospital
Collaborators
Sahlgrenska University Hospital, Sweden
1. Study Identification
Unique Protocol Identification Number
NCT05724004
Brief Title
Alectinib Followed by Concomitant Consolidation Radiation Therapy in Advanced NSCLC With ALK-rearrangement (A-SAB)
Acronym
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2023 (Actual)
Primary Completion Date
June 20, 2024 (Anticipated)
Study Completion Date
June 20, 2031 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska University Hospital
Collaborators
Sahlgrenska University Hospital, Sweden
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Single arm, multicenter, phase I/II study
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Radiotherapy + alectinib
Arm Type
Experimental
Arm Description
All patients receive consolidation radiation therapy to all active tumour lesions after induction treatment with alectinib.
Intervention Type
Radiation
Intervention Name(s)
SBRT/SRS/radiation therapy
Intervention Description
Consolidation radiation therapy (SBRT/SRS/moderately hypofractionated radiation therapy)
Primary Outcome Measure Information:
Title
Toxicity (safety)
Description
No and percentage of patients suffering grade 3-5 toxicity attributed to RT and within 6 months post RT).
Time Frame
6 months post radiation therapy
Title
Progression free survival (PFS)
Description
PFS-rate at 12 months (KM-estimated method). Successrate is 12-month-PFS-rate of 85%. Median PFS will also be measured
Time Frame
PFS rate at 12 months after initiation of alectinib
Secondary Outcome Measure Information:
Title
Overall survival
Description
OS-rate at 1-, 2-, 3- and 5 years post initiation of alectinib using the KM-method. Median OS will also be measured.
Time Frame
5 years
Title
Progression free survival II
Description
(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.
Time Frame
5 years
Title
Time to treatment failure
Description
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).
Time Frame
3 years
Title
Time to next therapy
Description
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).
Time Frame
5 years
Other Pre-specified Outcome Measures:
Title
Translational biomarker studies
Description
For plasma samples: extracellular vesicles isolated from plasma are profiled for protein and RNA expression with linkage to clinical response and tumor marker expression.
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
ALK-rearrangement
Adequate organ function to tolerate alectinib and clinical tolerance to alectinib
Stable disease (SD) or partial response (PR) after 2-3 months induction treatment with alectinib
Maximum 5 tumour lesions +/- thoracic lymph nodes active on an 18F-FDG-PET scan post induction treatment with alectinib
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)
Adequate organ function to tolerate SBRT/RT:
Fulfilment of dose constraints to adequate organs at risk
ECOG performance status (PS) 0-2
FEV1 ≥1 litre (only applicable for lung targets)
Age ≥ 20 years
Measurable lesions according to RECIST v 1.1
Signed written informed consent
Exclusion Criteria:
Leptomeningeal carcinosis (on MRI or in cerebrospinal fluid (CSF))
Persistent malignant pleural effusion, malignant pericardial effusion or malignant ascites after induction treatment
PD after 2-3-month-induction treatment with alectinib
Previous TKI, chemotherapy or immunotherapy (previous adjuvant chemotherapy for early stage NSCLC is allowed) for metastatic NSCLC
Previous RT for NSCLC (any stage)
Previous RT for any other cancer within the last 3 years possibly interfering with the planned RT within this study
Life expectancy of less than 6 months
Inability to understand given information or undergo study procedures according to protocol.
Has evidence or a past medical history of interstitial lung disease or active, non-infectious pneumonitis or known pulmonary fibrosis.
Pregnant or breast-feeding. Patients must agree to use safe contraception during and for 3 months after study treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karin Lindberg, MD, PhD
Phone
+46851770000
Email
karin.lindberg@ki.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karin Lindberg, MD, PhD
Organizational Affiliation
Karolinska University Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katja Tobin, PhD
Phone
+46851770000
Email
katja.tobin@regionstockholm.se
First Name & Middle Initial & Last Name & Degree
Karin Lindberg, MD, PhD
First Name & Middle Initial & Last Name & Degree
Andreas Hallqvist, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Alectinib Followed by Concomitant Consolidation Radiation Therapy in Advanced NSCLC With ALK-rearrangement (A-SAB)
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