About this trial
The ProTarget study is a phase II, prospective, non-randomized clinical trial with the primary purpose of investigating the safety and efficacy of commercially available cancer drugs that target specific changes in cancer cell DNA to treat patients with advanced cancer. The primary endpoint is anti-tumor activity or stable disease documented after 16 weeks of experimental drug treatment. The drugs used in the trial have been approved by EMA/FDA for the treatment of certain cancers. Choice of drug is based on whether the patient's cancer cells contain precisely the DNA change (i) targeted by the EMA/FDA-approved drug or (ii) related to sensitivity to the EMA/FDA-approved drug. The trial drug is thus not approved by the EMA/FDA or in Denmark for the treatment of the patient's cancer - it is so-called "off-label use". The secondary purposes are:
* To detect side effects in patients treated with commercially available targeted cancer drugs. * Performing biomarker analyzes, including (but not limited to) whole-genome analysis (WGS) on a fresh tumor tissue sample (biopsy) at baseline and progression. * To investigate mechanisms of resistance using recurrent / serial fresh tumor biopsies for WGS and so-called liquid biopsies, which are blood samples in which the cancer cell DNA is analyzed.
The secondary endpoints include response duration, progression-free survival, and overall survival.
Eligibility criteria
Qualifiers
Patient (age≥ 18 years) with a histologically-proven locally advanced or metastatic malignant disease who is no longer benefitting from standard anti-cancer treatment or for whom, in the opinion of the investigator, no such treatment is available or indicated.
ECOG performance status 0-2
Patients must have acceptable organ function as defined below. However, as noted above, drug-specific inclusion/
Disqualifiers
Absolute neutrophil count ≥ 1500 µl
Hemoglobin > 5.6 mmol/l
Platelets > 75,000/µl
Total bilirubin < 1.5 x institutional upper limit of normal (ULN)
Trial design
Treatments tested in this trial
- Alectinib
- Atezolizumab
- Avelumab
- Axitinib
- Erlotinib
- Vemurafenib plus Cobimetinib (combination)
- Trastuzumab plus Pertuzumab (combination)
- Trastuzumab emtansine
- Vismodegib
- Niraparib
Treatment groups
10
Treatment groupsSee each treatment group below.
Sponsors and collaborators
Ulrik Lassen
Lead sponsor
Rigshospitalet, Denmark
Sponsor institution
Roche Pharma AG
Collaborator
Pfizer
Collaborator
GlaxoSmithKline
Collaborator