Finnish national phase 2 study to evaluate targeted drug treatment in advanced cancer.
- Conditions
- Patients with an advanced solid tumor for which standard treatment options no longer exist and with acceptable performance status and organ function with a potentially actionable variant as revealed by a genomic, RNA-molecular or protein expression test.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-000689-14-FI
- Lead Sponsor
- Helsinki University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 250
1.Adult (age >18 years) patient with a histologically-confirmed locally advanced or metastatic solid tumor including lymphoma 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:
a.Absolute neutrophil count = 1.5 x 109/l
b.Hemoglobin > 8.0 mmol/l, without blood transfusion within 7 days
c.Platelets > 75 x 109/l
d.Total bilirubin < 1.5 x ULN
e.AST and ALT < 3 x institutional ULN (or < 5 x ULN in patients with known hepatic metastases)
f.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 for patients with solid tumors, or according to Lugano, RANO, PCWG3 or GCIG criteria (please refer to appendices for further details) [17-19].
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 as defined in Section 5. The test results (full pathology or molecular diagnostics report) must be uploaded in the eCRF.
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 (see section 5).
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.
For each drug included in this protocol, specific inclusion criteria (based on the Package Insert or manufacturers recommendations) may also apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number
1.Ongoing toxicity > grade 2, other than alopecia or > grade 1 neuropathy.
2.Patient is receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement). Required wash out period prior to starting study treatment is at least two weeks. An exception is made for:
a.Patients suffering from CRPC are allowed to continue androgen deprivation therapy.
b.Medications that are prescribed for supportive care but may potentially have an anti-cancer effect (e.g., megestrol acetate, bisphosphonates). These medications must have been started = 1 week prior to enrollment on this study.
3. Received colony-stimulating factors (eg, G-CSF, GM-CSF or
recombinant EPO) within 14 days prior to the first dose of study
intervention
4.Patient is pregnant or nursing.
5.Patients with known active progressive brain metastases. Patients with previously treated brain metastases are eligible, provided that the patient is clinically stable and off steroids for at least 4 weeks prior to study initiation.
6.Additional exclusion criteria specific for GBM patients:
a.Patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). EIAED are prohibited. Patients previously on EIAED must be switched to non-EIAED at least 2 weeks prior to randomization.
b.No radiotherapy within the three months prior to the diagnosis of progression unless for palliative intent to treat pain symptoms.
c.No radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven.
7.Patients with clinically significant preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure are not eligible.
8.Patients with known left ventricular ejection fraction (LVEF) < 45% are not eligible
9.Patients with stroke (including TIA) or acute myocardial infarction within 3 months before the first dose of study treatment are not eligible
10.Patients with any other clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations.
For each drug included in this protocol, specific exclusion criteria (based on the Package Insert or manufacturers recommendations) may also apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the anti-tumor activity and toxicity of anti-cancer drugs that are approved or under review by EMA, FDA or PMDA, and are used for treatment of patients with advanced solid tumors that harbour a DNA-, RNA or protein expression variant previously identified as target for a certain drug or which predicts sensitivity to a certain drug.;Secondary Objective: •To perform refined biomarker analyses including (but not limited to) next generation sequencing on a fresh tumor and liquid biopsies<br>•To define possible pathway activations and resistance mechanism facilitating progression to given therapies.<br>;Primary end point(s): •Disease control rate (defined as patients by CR, PR, SD);Timepoint(s) of evaluation of this end point: At 16 wks after treatment initiation
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Duration of treatment on study (time on drug) <br>•Treatment-related grade =3 and serious adverse events<br>•Best overall response (defined as patients by CR, PR, SD)<br>•Progression free survival<br>•Overall survival<br>;Timepoint(s) of evaluation of this end point: •end of treatment<br>•During the whole study<br>•wk 16<br>•until progression<br>•end of treatment