None listed
Conditions
Brief summary
What is ASPiRATION? ASPiRATION is a clinical trial that is testing a new approach to providing personalised treatments for patients with newly diagnosed lung cancer through comprehensive genomic testing of patient’s tumour tissue. The ASPiRATION study is being conducted as part of a larger research project called the Molecular Screening and Therapeutics (MoST) Program. In Australia, standard of care tumour testing for lung cancer patients has the ability to identify changes in three genes: EGFR, ALK & ROS1, for which drugs are available on the Pharmaceutical Benefits Scheme (PBS). If a patient is suitable for ASPiRATION, their tumour will also be tested using a technique called comprehensive genomic profiling (CGP), often referred to as molecular screening and/or profiling. This technique allows to look at changes in hundreds of genes in a single test. After a patient’s tumour is tested, a report is sent to the referring oncologist with information on (i) Any genetic biomarkers that were identified in the tumour and (ii) The types of treatment that may be suitable. Who is it for? a. Adults (>= 18 years of age) with newly diagnosed pathologically confirmed non-squamous non-small cell lung cancer and sufficient tumour tissue for “molecular” testing b. Fit to be able to have treatment Study details: A small part of your tumour tissue, which was collected previously, will be used to identify a biomarker by doing a laboratory analysis (‘molecular screening’). You will be asked to provide information about your and your family’s health background, to donate a blood sample and complete some questionnaires. Results from molecular screening will be returned to all participants. These results may have implications for your treatment if a suitable biomarker is found. It is hoped this research will determine whether additional molecular screening can be feasibly integrated into Australian clinical practice for patients with metastatic non-squamous non-small cell lung cancer (mNSCLC).
Interventions
Molecular screening for actionable biomarkers to be used to guide therapy.
In parallel with standard of care (SoC) testing (e.g. IHC/FISH/PCR for EGFR, ALK and ROS1), Comprehensive Genomic Profiling (CGP) will be performed on tumour tissue after patient consent and assessment of suitability for the study. Existing ‘biobanked’ tissue samples will be used. A report containing any actionable genomic alterations and corresponding treatment recommendations will be issued to the treating clinician
As
Molecular screening for actionable biomarkers to be used to guide therapy. In parallel with standard of care (SoC) testing (e.g. IHC/FISH/PCR for EGFR, ALK and ROS1), Comprehensive Genomic Profiling (CGP) will be performed on tumour tissue after patient consent and assessment of suitability for the study. Existing ‘biobanked’ tissue samples will be used. A report containing any actionable genomic alterations and corresponding treatment recommendations will be issued to the treating clinician As part of the study participants will be asked to complete a series of questionnaires assessing health-related quality of life and psychosocial status. EuroQOL EQ-5D-5L quality of life and visual analogue scale will be measured at 5 timepoints: at time of patient consent to molecular screening in the ASPiRATION subprogram, at return of molecular screening report to treating clinician, and 6, 12 and 24 months after consent for molecular screening. The Garvan Institute of Medical Research will coordinate the molecular screening from archival tumour tissue. The core assays will be based on a genomic sequencing panel to cover a broad range of potentially actionable or biologically important cancer genes, with subsequent bioinformatics analysis. Examples of genes that will be assessed by CGP include BRAF non-V600, METex14, NTRK and many others. Patient tumour samples will also be assessed for biomarkers using relevant assays such as immunohistochemistry. Molecular screening results will be reviewed by a Molecular Tumour Board (MTB). The MTB is composed of suitably qualified clinical and basic science researchers with expertise in oncology, clinical trials, cancer biology, genomics, bioinformatics, molecular pathology, and clinical genetics. In addition, ex officio and ad hoc expertise may be called on to assist the MTB in decision-making. MTB members are either affiliated with the Garvan Institute of Medical Research, or an institute/hospital within the AGCMC network. MTB members attend an annual MTB masterclass, and sign a confidentiality deed poll prior to attendance. Options for treatment as a result of the screening will fall into 3 categories: 1. Targeted treatments currently reimbursed by the Australian government under the PBS; 2. Treatment on a MoST substudy or other clinical trials; 3. Expanded access programs, hospital or patient funded access to targeted treatments Participants who do not have an 'actionable' genomic alteration on SoC and CGP may be treated at the discretion of the treating clinician. As well as first line treatment, CGP results may also guide 2nd and subsequent lines of therapy at the discretion of the treating clinician. Subsequent molecular screening is not planned as part of this study. Repeat tissue sample acquisition may be considered by participant’s treating clinician if initial tumour tissue was not sufficient to obtain evaluable results. Study duration is expected as 4 years in total (2 years of recruitment and 2 years follow-up after consent to molecular screening).
Sponsors
Australian Genomic Cancer Medicine Centre
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients, aged 18 years and older, with newly diagnosed pathologically confirmed metastatic non-squamous non-small cell lung cancer (mNSCLC); a. Exception: patients with a typical pattern of disease recurrence within 12 months following primary resection may not require a confirmatory repeat biopsy, unless the diagnosis is unclear, such as an isolated pulmonary nodule, in which case repeat biopsy should be considered per standard practice; b. For mixed or other histologies the following is permitted: - Mixed adenosquamous where adenocarcinoma is dominant - Carcinoma not otherwise specified (NOS) favouring adenocarcinoma - Sarcomatoid carcinoma 2. ECOG performance status 0 or 1. 3. Sufficient tissue for molecular screening. 4. Willing and able to comply with study requirements. It is the intention to screen patients who are in principle willing to consider participation in a MoST substudy if they are found to have an appropriate tumour biomarker and are still eligible for enrolment at the time of the treatment phase; 5. Current enrolment or participation in another clinical study with an unregistered investigational product during the last 12 months, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study, must first be discussed the Study Team before study enrolment. 6. Signed, written informed consent to participate in molecular profiling and linkage to Medicare data. 7. Have not had any previous treatment for metastatic non-squamous NSCLC; a. For patients with symptomatic or bulky disease, where it would be detrimental to delay treatment, systemic therapy may be commenced at the investigator’s discretion whilst awaiting CGP results; b. Patients who have had prior treatment with curable intent are eligible. 8. Life expectancy of at least 12 weeks.
Exclusion criteria
1. Ineligible histology: - Mixed small cell lung cancer - Large cell neuroendocrine carcinoma 2. Comorbidities or conditions (e.g. psychiatric) which may contraindicate participation and/or ability to receive any systemic therapy(s); 3. Comorbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol; 4. History of another primary malignancy except for: a. Malignancy treated with curative intent and with no known active disease within 2 years before consent to molecular screening and of low potential risk for recurrence b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease c. Adequately treated carcinoma in situ without evidence of disease
Outcome results
None listed