Metastatic Cancer
Conditions
Keywords
Metastatic disease, Metastasis, Targeted therapy, Solid tumor, Personalized medicine, N-of-1 trial
Brief summary
The metastatic lesions may be very different from the primary tumor because of intrinsic tumor heterogenity, clonal selection through metastatic process and following previous cytotoxic treatments. Metastatic tumor harboring actionable targets or signaling pathways may respond to inhibitory agents directed against specific aberrations irrespective of tumor origin. In the MetAction study, patients will receive therapy based on molecular aberrations in the metastatic lesions, actionable target identification (ATI), rather than on histological tumor type. The ATI rate in an unselected metastatic patient population is uncertain, and response rates associated with ATI based targeted therapy have hardly been reported. In this perspective, The MetAction study is essentially a feasibility study aiming to tailor metastatic cancer therapy based on genomic profiles.
Detailed description
Recognizing the rapidly increasing number of drugs targeting specific molecular aberrations in cancer, it is necessary to define rational strategies to make such treatment available to Norwegian cancer patients.These targeted drugs are extremely costly and have significant side effects, although presumably to a lesser extent than many of the classic cytotoxic drugs available. Thus, in the interest of the patient in question and the society in general, it is important to give the right drug to the right patient and to the presumably right time in the disease course. Hitherto, most of the drugs in question are given in the palliative setting, i.e. to patients with disseminated metastatic disease. The metastatic lesion may be very different from the primary tumor, and hence, it is rational to analyze the tumor to be treated, the metastatic lesion(s), for the presence of molecular aberrations, rather than basing treatment decisions on molecular features known to be present in a particular tumor type or in the primary tumor.
Interventions
DRUGEMA-approved ATI based targeted therapy
All drugs that may be used in the study are approved by EMA for treatment of disseminated cancer in the palliative setting, but not for the particular tumor type in question.
Sponsors
The Research Council of Norway
Oslo University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Metastatic cancer and progression by RECIST 1.0 evaluated by internal review on at least one prior regimen of established palliative systemic therapies for advanced disease and eligibility for repeat biopsy sampling. The patient must have received ≥6 weeks of the previous treatment. Only patients who have no other standard treatment option or were the treatment option is considered to offer the patients only minor benefit may be included in the study. * Radiological evaluation intervals on last prior therapy (period A) must have been 6 to 12 weeks. * At least one measurable lesions (\>10mm on CT-scan) according to RECIST 1.0. * Age ≥ 18 years. Eastern Cooperative Oncology Group (ECOG) performance status 1 or lower. * Life expectancy of more than 3 months. * Adequate bone marrow function without current use of colony-stimulating factors: Neutrophils ≥1.5 x109/l; Platelets ≥100 x109/l; Hb \>10 g/dl, INR within normal level. * Adequate liver function: AST/ALT ≤5x ULN; Bilirubin ≤2x ULN, albumin \>30 g/l. * Adequate renal function: Creatinine ≤1.5x ULN. * Be able to use recommended dose of the selected targeted therapy as described in the drug specific SPC. * Be able to comply with the protocol. * Fertile men and women must be willing to use effective contraceptives. * Provide written (signed) informed consent to participate in the trial prior to any trial specific screening procedures.
Exclusion criteria
* Metastatic disease from more than one malignancy. * Untreated or symptomatic brain metastasis (patients must be symptom-free without the use of corticosteroids). * Any reason why, in the opinion of the investigator, the patient should not participate. * Pregnancy. * Breastfeeding * Anticoagulation with coumarin derivatives. * Radiation therapy within 4 weeks of start of treatment. * Need to use medications contraindicated according to SPC of the different drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | From date of initiation of study treatment until the date of first documented progression or date of death, from any cause, whichever came first, assessed up to 24 months. | Comparing the PFS using therapy selected by ATI in a patient's tumor (period B) with the PFS for the most recent therapy on which the patient had just experienced progression (period A). The ATI-selected therapy is defined as having benefit for the patient if PFS period B/PFS in period A ratio is ≥ 1.3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | From date of initiation of study treatment until the date of first documented progression, assessed up to 24 months. | The sum of partial responses (PS) plus complete responses (CR). |
| Overall survival (OS) | From date of initiation of study treatment until date of death, from any cause, assessed up to 24 months. | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Health Related Quality of Life (HRQoL) Questionnaire | From date of initiation of study treatment until date of end of study visit, an expected average of 4 months. | Assessed by the subject questionnaire EORTC Quality of Life Questionnaire Core 30 (QlQ-C30) at baseline, every 8 week during treatment and at end of study visit. |
| Overall clinical benefit rate (ORR + stable disease [SD] ≥ 6 months) | From date of initial response to date of first documented progression, assessed up to 24 months. | — |
| Toxicity grade 3-5 | From date of initiation of study treatment until date of follow-up visit, an expected average of 5 months. | — |
| ATI rate | From date of screening of first included patient until date of completion of screening phase, an expected time period of 24 months.. | — |
| PFS in ATI lesions only. | From date of initiation of study treatment until date of first documented progression in ATI lesions, assessed up to 24 months. | — |
Countries
Norway
Outcome results
None listed