Advanced Cancer, Solid Tumor, Haematological Malignancy
Conditions
Keywords
DRUP study
Brief summary
This is a prospective non-randomized national clinical phase 2 trial that aims to determine the efficacy and toxicity of targeted anticancer drugs or combinations that are approved or under review by EMA, FDA or PMDA and are used for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic, RNA-molecular or protein expression test.
Detailed description
This is a prospective non-randomized clinical trial that aims to determine the efficacy and toxicity of targeted anticancer drugs or combinations that are approved or under review by EMA, FDA or PMDA and are used for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic, RNA-molecular or protein expression test. The study also aims to facilitate patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing and further deeper analysis on tumor biopsies and/or liquid biopsies for biomarker analyses and resistance mechanisms. Eligible patients have an advanced cancer for which standard treatment options no longer exist and acceptable performance status and organ function. A tumour DNA, RNA or protein expression analysis is required and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Molecular profiling will be utilized to determine an appropriate drug(s) from among those available in the protocol. Drug selection will be guided by a list of potential profiles, the molecular tumor board and databases of identified targets for review and approval of the recommended treatment. The protocol-specified treatment will be administered to the patient once any drug- and disease specific eligibility criteria and overall study criteria are met. Data for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment will be collected for all patients receiving treatment within the trial. In addition, treatment related toxicity will be collected according to CTCAE 5.0.
Interventions
DRUGAlectinib
ALK
DRUGCobimetinib
MEK1, MEK2
DRUGVismodegib
Hedgehog
DRUGTrastuzumab+Pertuzumab
HER2
DRUGEntrectinib
NTRK/ ROS1, ALK
DRUGAtezolizumab
PD-L1
DRUGVemurafenib
BRAF V600
DRUGRegorafenib
KIT/BRAF, RET
DRUGApalutamide
AR
DRUGAbemaciclib
CDK4/6
DRUGTepotinib
MET ex14
DRUGDabrafenib
RAF
DRUGTrametinib
MEK1, MEK2
RAF, MEK1, MEK2
DRUGPemigatinib
FGFR2
Sponsors
Helsinki University Central Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Adult (age \>18 years) patient with a histologically-confirmed locally advanced or metastatic cancer who is no longer benefitting from standard anti-cancer treatment or for whom no such treatment is available or indicated. 2. ECOG performance status 0-2 3. Patients must have acceptable organ function as defined below. However, specific inclusion/
Exclusion criteria
specified in the drug-specific study manual will take precedence: 1. Absolute neutrophil count ≥ 1.5 x 109/l 2. Hemoglobin \> 8.0 mmol/l, without blood transfusion within 7 days 3. Platelets \> 75 x 109/l (not applicable for hematological patients) 4. Total bilirubin \< 1.5 x ULN 5. AST and ALT \< 3 x institutional ULN (or \< 5 x ULN in patients with known hepatic metastases) 6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 40 mL/min/1.73 m2 4. Patients must have objectively evaluable or measurable disease (by physical or radiographic examination, according to RECIST v1.1, Lugano, IWG and ELN-AML, IMWG, RANO, GCIG, iRESIST or PCWG3. 5. Results must be available from a tumor molecular profiling. Eligible tests may include any of the following technologies: fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), comparative genomic hybridization (CGH), next generation sequencing (NGS) or immunohistochemistry (IHC). The test may have been performed on the primary tumor or a metastatic lesion, in a diagnostic laboratory or within the context of another commercial platform (eg Foundation Medicine), and must reveal a potentially actionable variant. 6. Patients must have a tumor profile for which treatment with one of the approved (or under revision for approval) targeted anti-cancer drugs included in this study has potential clinical benefit based on preclinical data or clinical information. 7. A new (obtained ≤6 months before inclusion after which no further anti-cancer therapy is allowed) fresh frozen and FFPE tumor biopsy specimen or liquid biopsy for extensive biomarker testing is mandatory before the start of treatment with a targeted agent included in the protocol. 8. Ability to understand and the willingness to sign a written informed consent document and comply to the protocol. 9. For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome. 10. Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy. Male patients should avoid impregnating a female partner. Male patients, even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from sexual intercourse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate | 16 weeks | Disease control rate at 16 weeks after treatment initiation (defined as patients by CR, PR, SD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of treatment | 5 years | Time on drug |
| Adverse Events | 5 years | Treatment-related grade ≥3 and serious adverse events |
| Overall response | 5 years | Best overall response (defined as patients by CR, PR, SD) |
| PFS | 5 years | Progression free survival |
| OS | 5 years | Overall survival |
Countries
Finland
Contacts
Primary ContactTanja Juslin
Outcome results
None listed