Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity (NCT02314481) | Clinical Trial Compass
CompletedPhase 2
Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity
United Kingdom50 participantsStarted 2017-05-12
Plain-language summary
DARWIN II is a multi-arm non-randomised phase II trial, Eligible patient will be those who relapse with NSCLC (clinical trials.gov ref. NCT02183883). .
The trial will investigate assess if intra-tumour heterogeneity (clonal vs subclonal actionable mutation) is associated with PFS.
Patients without an actionable mutation will receive MPDL3280A (atezolizumab), a monoclonal antibody targeting anti-PDL1, as monotherapy or in combination with chemotherapy, The options for combination therapy will vary depending on the histology of the NSCLC (i.e. non-squamous or squamous).
Patients with BRAFV600 mutations, HER2 Amplification, ALK/RET gene rearrangements will be enrolled into arms treating with vemurafenib, trastuzumab emtansine and alectinib respectively.
DARWIN II will include extensive exploratory biomarker analysis to investigate a number of genomic and immune markers that may predict response to MPDL3280A (atezolizumab) and help guide future clinical trial design.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
TRACERx Patients
* Multi-region sequencing data of the primary tumour available.
* TRACERx patients should be approached for a biopsy of the active locally advanced or metastatic disease but this is not mandated for DARWIN2 trial inclusion. Consent for this biopsy will be obtained within the TRACERx study.
Non-TRACERx patients
Minimum requirement:
• Fresh frozen biopsy of active locally advanced or metastatic disease OR at least two FFPE regions from primary tumour available
Optimal Tissue availability:
* Multi-region tissue of the primary tumour available (FFPE or fresh frozen) AND a fresh frozen biopsy of active locally advanced or metastatic disease
* OR One archival biopsy tissue sample (FFPE or fresh frozen)/pre-extracted DNA sample AND one fresh frozen biopsy of active locally advanced or metastatic disease
* OR Two fresh biopsies of active locally advanced or metastatic disease that are spatially separated e.g. one lymph node biopsy AND one lung biopsy.
Consent for the biopsy(ies) of the active locally advanced or metastatic disease for non-TRACERx patients must be taken using the DARWIN2 'trial entry tissue sample' consent form.
* Arm 1: Absence of any actionable mutation
* ECOG PS 0-1 for MPDL3280A in combination with chemotherapy
* ECOG PS 0-2 for MPDL3280A monotherapy.
* Ability to avoid ibuprofen 2 days before, the day of, and 2 days following administration of Pemetrexed (combination therapy involving pemetrexed only)
* Abili…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Progression free survival (PFS)
Timeframe: From date of registration until the date of first documented progression or death (whichever occurs first), assessed up to 84 months
2
Overall survival
Timeframe: From date of registration until death date, assessed up to 84 months