ABOUT THIS STUDY
1. Adult (age >18 years) patient with a histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma who is no longer benefitting from standard anti-cancer treatment or for whom no such treatment is available or indicated.
* For GBM patients: Histologically confirmed recurrent or de novo glioblastoma (primary), with unequivocal first progression after radiotherapy and concurrent/adjuvant chemotherapy, at least 3 months after the concomitant part of the chemo-radiotherapy, and with stable or decreasing dosage of steroids for at least 7 days prior to the baseline MRI scan.
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 > 5.6 mmol/l
3. Platelets > 75 x 109/l
4. Total bilirubin < 2 x ULN
5. AST (SGOT) and ALT (SGPT) < 2.5 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 ≥ 50 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 IMWG, Lugano, RANO or GCIG criteria, resp., for patients with multiple myeloma, non-Hodgkin lymphoma, glioblastoma or ovarian cancer in case of CA125-based evaluation (please refer to appendices for further details) [16, 17].
5. Results must be available from a tumor genomic or protein expression test. 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 deposit, in a diagnostic laboratory or within the context of another CPCT study, 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 single agent treatment with one of the EMA approved 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 ≤2 months before inclusion, and without any type of anti-cancer therapy within those ≤2 months ) fresh frozen tumor biopsy specimen for extensive biomarker testing is mandatory before the start of treatment with a targeted agent included in the protocol.
*For GBM patients:
The mandatory fresh frozen tumor biopsy sample can be obtained through standard-of-care surgical procedures (i.e., performed at progression, for cytoreduction, to proof progressive disease, or to reduce mass effect on the surrounding brain tissue). Thus, surgical procedures are standard-of-care and not part of trial participation. Fresh frozen tumor tissue must have been obtained ≤2 months before inclusion, and without any type of anti-cancer therapy within those ≤2 months. After surgical procedures, patients must meet the following inclusion criteria:
i. Surgery must have confirmed the recurrence. ii. A post-surgery MRI should be available within 48 hours following surgery, and must show residual and measurable disease.
iii. Craniotomy or intracranial biopsy site must be adequately healed free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of study inclusion.
8. Ability to understand and the willingness to sign a written informed consent document.
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 foetus, 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.
1. Ongoing toxicity > grade 2, other than alopecia.
2. Patient is receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or
hormonal other than for replacement) except for 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. Patient is pregnant or nursing.
4. Patients with known active progressive brain metastases. Patients with previously
treated brain metastases are eligible, provided that the patient has not experienced a
seizure or had a clinically significant change in neurological status within the 3
months prior to registration. All patients with previously treated brain metastases
must be stable for at least 1 month after completion of treatment and off steroid
treatment prior to study enrollment.
* Additional exclusion criteria specific for glioblastoma patients:
1. 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.
2. No radiotherapy within the three months prior to the diagnosis of progression.
3. No radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or
brachytherapy unless the recurrence is histologically proven.
5. 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.
6. Patients with known left ventricular ejection fraction (LVEF) < 40% are not eligible
7. Patients with stroke (including TIA) or acute myocardial infarction within 3 months
before the first dose of study treatment are not eligible
8. 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 inclusion and exclusion criteria (based
on the Package Insert or manufacturers recommendations) may also apply. These can be found
in the supplemental information about each agent included in the drug-specific study
manuals. Drug-specific inclusion and exclusion criteria will take precedence over the
inclusion/exclusion criteria listed above.
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