Program Status
RecruitingPhase
Phase 2Prior Immunotherapy Allowed
YesCRC-directed Trial
NoDrugs
Abemaciclib, afatinib, Alectinib, Alpelisib, Atezolizumab and Bevacizumab, Axitinib, Cabozantinib, Crizotinib, Dabrafenib, Dabrafenib and trametinib, Dacomitinib, durvalumab, Entrectinib, Erdafitinib, Erlotinib, Ipilimumab and nivolumab, Lenvatinib, lorlatinib, Nilotinib, Nivolumab, Olaparib, palbociclib, panitumumab, Pembrolizumab, Regorafenib, ribociclib, Rucaparib, Sunitinib, Talazoparib, Trametinib, Trastuzumab and Pertuzumab (combination treatment), Vemurafenib and Cobimetinib (combination treatment), VismodegibTags
MSI-H/ MMRd, MSS/ MMRpComments
Similar to the TAPUR and NCI-MATCH trials in the United States, this European trial potentially offers approved drug access (drugs approved for cancers other than CRC) to CRC patients with genetic profiles indicating potential therapeutic patient (for example, but not limited to HER2, BRAF based CRC). Publication in Nature, Sep 2019 (see Helpful Links)
Location | Location Status |
---|---|
Netherlands | |
Noordwest ziekenhuisgroep Alkmaar (NWZ) Alkmaar |
Recruiting |
Ziekenhuisgroep Twente Almelo |
Recruiting |
Meander medisch centrum Amersfoort 3818 ES |
Recruiting |
Netherlands Cancer Institute Amsterdam 1066CX |
Recruiting |
Amsterdam UMC, locatie VUmc Amsterdam 1081 HV |
Recruiting |
Amsterdam UMC, locatie AMC Amsterdam 1105AZ |
Active, not recruiting |
Onze Lieve Vrouwe Gasthuis (OLVG) Amsterdam |
Recruiting |
Gelre ziekenhuizen Apeldoorn |
Recruiting |
Rijnstate ziekenhuis Arnhem |
Recruiting |
Amphia Ziekenhuis Breda |
Recruiting |
Reiner de Graaf Gasthuis Delft |
Recruiting |
Haaglanden medisch centrum Den Haag |
Recruiting |
Haga ziekenhuis Den Haag |
Recruiting |
Deventer ziekenhuis Deventer |
Recruiting |
Nij Smellinghe Ziekenhuis Drachten |
Recruiting |
Ziekenhuis Gelderse Vallei Ede |
Recruiting |
Maxima Medisch Centrum Eindhoven 5631 BM |
Recruiting |
Zuyderland medisch centrum Geleen 6162 BG |
Recruiting |
Rivas zorggroep Gorinchem |
Recruiting |
Martini ziekenhuis Groningen |
Recruiting |
University Medical Center Groningen Groningen |
Recruiting |
Spaarne gasthuis Haarlem |
Recruiting |
Tergooi MC Hilversum |
Not yet recruiting |
Treant zorggroep Hoogeveen |
Recruiting |
Medisch Centrum Leeuwaarden Leeuwarden |
Recruiting |
Leiden University Medical Center Leiden |
Recruiting |
Maastricht University Medical Center Maastricht |
Recruiting |
St. Antonius ziekenhuis Nieuwegein |
Recruiting |
Radboud umc NIjmegen 6225GA |
Recruiting |
Bravis ziekenhuis Roosendaal |
Recruiting |
St. Fransicus Gasthuis Rotterdam 3045 PM |
Recruiting |
Erasmus MC Rotterdam |
Recruiting |
Elisabeth-TweeSteden Ziekenhuis Tilburg 5022 GC |
Recruiting |
University Medical Center Utrecht Utrecht 3584CX |
Recruiting |
VieCuri medisch centrum Venlo |
Recruiting |
Isala klinieken Zwolle |
Recruiting |
Contacts
Inclusion Criteria
Inclusion Criteria:
Adult (age >18 years) patient with a histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or B cell non-Hodgkin lymphomawith symptomatic disease progression or progression according to RECIST-criteria after standard anti-cancer treatment or for whom no such treatment is available or indicated.
* For patients with a primary brain tumor: Histologically confirmed recurrent or de novo primary brain tumor, with unequivocal progression after prior therapy, at least 3 months after radiotherapy (either first line chemo-radiotherapy or re-irradiation), and with stable or decreasing dosage of steroids for at least 7 days prior to the baseline MRI scan.
ECOG performance status 0-2
Patients must have acceptable organ function as defined below. However, specific inclusion/
Exclusion Criteria
exclusion criteria specified in the drug-specific study manual will take precedence:
Absolute neutrophil count ≥ 1.5 x 109/l
Hemoglobin > 5.6 mmol/l
Platelets > 75 x 109/l
Total bilirubin < 2 x ULN
AST (SGOT) and ALT (SGPT) < 2.5 x institutional ULN (or < 5 x ULN in patients with known hepatic metastases)
Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2
Patients must have objectively 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).
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.
Patients must have a tumor profile for which treatment with one of the FDA and / or EMA 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).
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. Alternatively, fresh frozen tumor tissue acquired in the context of a standard care procedure may be used, provided that no systemic anti-cancer treatment was given between the procedure and start of study treatment within DRUP.
The following exceptions are made:
a. An exception is made for patients with a primary brain tumor, only if the mandatory DRUP pre-treatment biopsy for biomarker analysis cannot safely be obtained:
The fresh frozen tumor biopsy sample may be replaced by fresh frozen tumor tissue, obtained earlier from recurrent disease, as part of standard of care surgical procedure (i.e., performed at progression)
If no fresh frozen tumor tissue is available for NGS, and the risk of obtaining a new tumor biopsy is considered too high, no biopsy will be required. In this case, the study coordinators must be informed in advance, and there will be no reimbursement for the biopsy procedure.
b. In case WGS is performed on tumor tissue outside the context of a clinical trial before inclusion, and without any type of anti-cancer therapy between the collection of tissue and inclusion in DRUP, this can replace the DRUP pre-treatment biopsy, provided that the patient gives consent to use his/her WGS data for biomarker analysis in DRUP.
c. An exception is made for patients that underwent an allogeneic hematopoietic stem cell transplantation prior to study enrollment, since this will prevent a correct WGS analysis due to a mismatch between the biopsy specimen and the required blood sample.
Ability to understand and the willingness to sign a written informed consent document.
For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
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.
Exclusion Criteria:
Ongoing toxicity > grade 2, other than alopecia.
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:
Patients suffering from CRPC are allowed to continue androgen deprivation therapy.
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.
Patient is pregnant or nursing.
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:
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.
No radiotherapy within the three months prior to the diagnosis of progression.
No radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven.
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.
Patients with known left ventricular ejection fraction (LVEF) < 40% are not eligible
Patients with stroke (including TIA) or acute myocardial infarction within 3 months before the first dose of study treatment are not eligible
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.