Cancer Metastatic
Conditions
Brief summary
IMPRESS-Norway is a prospective, non-randomized clinical trial evaluating efficacy of commercially available, anti-cancer drugs prescribed for patients with advanced cancer diagnosed with potentially actionable alterations as revealed by molecular diagnostics. IMPRESS-Norway is a nation-wide study and all hospitals with an oncology and / or hematology department will be invited to participate in the study. The study will use a combined umbrella and basket design and a Simon two-stage model of expanding cohorts to follow up potentially effective combinations of biomarker and drug on specific indications. Sampling of biological material will be performed at presentation, during treatment and upon progression. Additional biomarker and translational analyses including whole genome sequencing (WGS) on tumour material and liquid biopsies, identifying mechanisms underlying drug sensitivity versus resistance will be performed.
Detailed description
Eligible patients have an advanced malignancy already treated with standard treatment, acceptable performance status and organ function, with no other suitable clinical trial available in Norway. A molecular test performed at a study specific reference laboratory has identified a potentially targetable molecular profile. Next, a suitable drug should be available from the trial drug armamentarium. Finally, if the patient fulfils the inclusion criteria and is accepted for the trial, a second tumour biopsy (snap-frozen)/ tumour material for WGS will be sampled. Patients enrolled in the study will enter an existing cohort, or, in case a suitable cohort does not exist, a new cohort can be opened. One cohort will consist of one diagnostic subgroup, one drug (or one drug-combination) and one molecular marker. The choice of drug(s) will be supported by a list of potential profiles. In addition, available knowledge from the literature will be used to prepare discussion in a national molecular tumour board, which will provide a treatment recommendation to the treating physician and the study doctors . The protocol-specified treatment may be administered to the patient once drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future biomarker studies and research on responders versus non-responders. All patients who receive treatment with a drug available in the protocol will be monitored for standard efficacy outcomes including tumour response, progression-free and overall survival as well as study specific measures as duration of treatment. Patients that are screened, but not included into any cohorts will be followed for 16 weeks for survival and clinical course of disease. Treatment-related toxicities (CTCAE grade 3-5) will be evaluated. Study-specific treatment and outcome data including results from the molecular screening will be reported to the Cancer Registry of Norway. Long-term follow up data using the Cancer Registry of Norway and information from The Norwegian Patient Registry, The Norwegian Prescription Database and Primary patient- and user Register (KPR) will be collected on all patients screened.
Interventions
DRUGAtezolizumab
drugs used outside indication, based on biomarker
Sponsors
Haukeland University Hospital
St. Olavs Hospital
University Hospital of North Norway
University Hospital, Akershus
Vestre Viken Hospital Trust
Hospital of Southern Norway Trust
Ostfold Hospital Trust
The Hospital of Vestfold
Helse Stavanger HF
Nordlandssykehuset HF
Sykehuset Innlandet HF
Helse Forde
Helse Fonna
Helse Nord-Trøndelag HF
Helse Møre og Romsdal HF
Sykehuset Telemark
Lovisenberg Diakonale Hospital
Oslo University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Simon 2-stage Basket-Umbrella
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type of Participant and Health status 1. Patient with a pathology-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. 2. ECOG performance status 0-2. 3. For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome. 4. Patients must have acceptable organ function as defined below. However, as noted above, drug-specific inclusion/
Exclusion criteria
specified in the drug-specific study manuals for each agent will take precedence for this and all inclusion criteria (exceptions for haematological diagnoses): 1. Absolute neutrophil count ≥ 1.5 x109 / L 2. Hemoglobin \> 9 g/dl 3. Platelets \> 75,000/µl 4. Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) 5. AST (SGOT) and ALT(SGPT) \< 2.5 x institutional upper limit of normal (ULN) (or \< 5 x ULN in patients with known hepatic metastases) 6. Calculated or measured creatinine clearance ≥ 40 mL/min/1.73 m2. 5. Patients must have measurable or evaluable disease. RECIST v1.1 (10, 18) will be used for patients with solid tumours. For patients with multiple myeloma or non-Hodgkin lymphoma, IMWG response criteria (19) and CHESON/Lugano guidelines (20) will be used, resp. For glioblastoma patients, RANO criteria will be used (21). iRECIST will be used for immunotherapy-cohorts. IWG response criteria will be used for haematological cancers. Patients whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumour marker only) are NOT eligible, with the exception of CA-125 for ovarian cancer and PSA for prostate cancer (22). 6. Results must be available from a genomic / molecular test performed in a preapproved laboratory (Section 10.15). The test used to qualify a patient for participation in IMPRESS-Norway may have been performed on any specimen of the patient's tumour obtained at any point during the patient's care at the discretion of the patient's treating physician. Genomic assays performed on cell-free DNA in plasma (liquid biopsies) will also be acceptable if the genomic analysis is performed as defined in Section 10.5. NGS analyses will be performed on a newly sampled biopsy if possible. Information from these analyses might be used upon progression, for evaluation of possible new cohort-inclusion. 7. Have a genomic profile for which treatment with one of the approved targeted anti-cancer therapies included in this study has potential clinical benefit see Section 4.3.5 Note: Eligible genomic tests may include any of the following technologies and equivalent techniques: Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) (incl nanostring), array-based copy number analysis (CNV), sanger sequencing (SS), RNA sequencing, gene panels or whole exome sequencing (WES) by next generation sequencing (NGS). The test may have been performed on a fresh (frozen or in RNA-later) or paraffin-embedded specimen of the primary tumour or a metastatic deposit or on cell-free DNA derived from liquid biopsies (like for instance peripheral blood plasma), as determined by the treating physician, and must reveal a potentially actionable genomic variant or protein overexpression as defined in Section 4.3. 8. Patients must meet drug-specific eligibility requirements for the drug selected by the investigator. Sex and Contraceptive/Barrier Requirements 9.8. Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate highly effective methods of contraception for the duration of study participation, and for 4 to 24 months following completion of study therapy as defined in Section 11.4. 10.9. Female participants must have a negative highly sensitive pregnancy test \<1 month prior to inclusion. 11.10. Male patients should avoid impregnating a female partner. Male study patients must agree to one of the following: practice effective barrier contraception as described under sec. 11.4 during the entire study treatment period and through a certain time after the last dose of study drug. Details are given in the Drug specific amendment. Informed Consent 12.11. Ability to understand and the willingness to sign a written informed consent/assent document as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Guardians / parents can act on behalf of children.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 16 weeks clinical response | 16 weeks | To determine percentage of patients who have not progression on treatment. Not progression is complete response, partial response and stable disease. |
| Access to drugs for patients | 4 years | To evaluate percentage of patients included in treatment cohorts |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival of patients starting treatment in the study | 4 years | Progression-free survival Time from treatment initiation to progression of disease |
| Overall survival of patients starting treatment in the study | 4 years | Time from treatment initiation to death Duration of time on drug Time from the molecular diagnostics first informed consent to starting treatment |
| Biomarker analyses | 4 years | • Estimate the percentage of patients eligible for analyses only by liquid biopsies |
| • Access of tumour tissue biopsy across and within tumour types | 4 years | • Number of tumour / molecular assessments per patient / cohort |
Countries
Norway
Contacts
Primary ContactÅslaug Helland, MD PhD
Backup ContactGro LIve Fagereng, PhD
Outcome results
None listed