Trial Details

Trial status:

In follow-up (non-recruiting)

Recruitment start date:

12/05/2016

Funder:

F.Hoffmann-La Roche Ltd

Sponsor:

UCL

Chief Investigator:

Charles Swanton

Recruitment target:

119

EudraCT number:

2014-005456-25

Contact details:

ctc.darwin2@ucl.ac.uk

Note: For enquiries only. DO NOT use for clinical referrals.

DARWIN 2

Deciphering Anti-tumour Response and Resistance With INtratumour Heterogeneity

Description

Design: DARWIN II is a phase II multi-centre non-randomised trial for NSCLC patients to study tumour heterogeneity using genomic analysis. The trial will only be opened in sites participating in the TRACERx study.

Treatment:

Arm 1 patients will receive MPDL3280A (Atezolizumab) for 24 cycles. After completion of treatment, patients will be followed up 3 monthly until progression or for 2 years post the end of treatment.

Arm 2/Arm 3 patients will receive Vemurafenib (Arm 2) or Alectinib (Arm 3) twice a day until disease progression. For administrative purposes treatment is divided into 28 day cycles. Patients will be seen monthly.

Arm 4 patients will receive Trastuzumab Entamsine on day 1 of a 21 day cycle, and should be treated until disease progression.

For TRACERx patients, follow up will then continue under the TRACERx protocol for as long as TRACERx remains open. For non-TRACERx patients or where TRACERx is closed, patients will revert to routine follow up.

Key inclusion/exclusion criteria: Patients must have multi-region sequencing data of the primary tumour available and must be willing to have a biopsy of relapsed disease. Patients must have the absence of sensitizing EGFR mutation. Non-TRACERx patients must have at least two archival tissue/DNA samples available. Patients must not have a history of other malignancy, previous anti-cancer therapy (within 14 days) or palliative radiotherapy (within 1 week) prior to registration. Patients with pre-exisiting interstitial lung disease or that are suitable for radical radiotherapy are excluded.

Duration of recruitment: Timelines are dependent on the recruitment and subsequent relapse of patients on the TRACERx study – approx. 4 years.

Aim

The trial aims to explore whether mutational burden and neo-antigen repertoire predict for improved progression free survival and anti-PDL1 mAb immunotherapy for those patients with stage III/IV NSCLC (patients in whose tumour lacks an actionable mutation).

For those patients with actionable BRAFV600 mutations, HER2 amplification and HER2 IHC2+/3+ or ALK/RET gene fusions this trial aims to assess the role of clonal dominance on the mechanisms of action and response to Vemurafenib, Trastuzumab Emtansine and Alectinib, respectively.

Contact the trial team

View trial summary

View trial documents

Cancer Research UK & UCL Cancer Trials Centre
University College London
90 Tottenham Court Road
London
W1T 4TJ

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Email:
ctc.enquiries@ucl.ac.uk
Telephone:
+44 (0)20 7679 9898 (General CTC Enquiries)
Fax:
020 7679 9899

CTC staff

University College London, Gower Street, London, WC1E 6BT +44 (0)20 7679 2000