A Phase 2 interventional study of Panitumumab and Olaparib in Cancer, Tumors and Neoplasm, sponsored by The Netherlands Cancer Institute. Recruiting at 36 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-01-24.
Sponsored by The Netherlands Cancer Institute · Phase 2, Interventional, and Treatment
This is a prospective, non-randomized clinical trial that aims to describe the efficacy and toxicity of commercially available, targeted anticancer drugs* prescribed for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic or protein expression test. The study also aims to simplify patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing on tumor biopsies for biomarker analyses. Eligible patients have an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function. A genomic or protein expression test must have been performed on the tumor and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Results from the molecular profiling test will be used to determine an appropriate drug(s) from among those available in the protocol. The choice of drug will be supported by a list of potential profiles, a molecular tumor board, a knowledge library and by study coordinators for review and approval of the match. The protocol-specified treatment will be administered to the patient once any drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future genetic studies. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment. In addition, treatment related toxicity will be evaluated.
Problem description: evidence is building that matching targeted agents to tumor characteristics can improve outcomes. Such reports have fueled interest among patients and physicians to use molecular testing for treatment planning when standard treatment options have been exhausted. When oncologists aim to provide such personalized treatment to their patients though, obtaining the drugs can be challenging since off-label prescribing, while legal, is generally not reimbursed by insurance companies. Furthermore, outcomes of off-label treatment in routine clinical practice are not systematically recorded. As a result, the research and clinical communities have limited insight in these outcomes, leading to repetitive use of ineffective treatment for some tumor types, while effective treatment strategies might be missed for others. The latter is especially relevant for 'orphan diseases', that are too rare to conduct formal phase II and III trials. In summary, there is a lack of access to potentially effective therapy on one hand, and a lack of knowledge on broader use of such therapies on the other, altogether leading to sub-optimal use of available resources.
Envisioned solution and study aim: creation of a drug-access program, in which patients are treated with registered targeted therapy matched to their molecular tumor profile, and in which the outcomes of such therapies are recorded systematically, per tumor profile and tumor type (this is important since it is becoming increasingly clear that the tissue of origin is an important determinant of outcome of genetic abnormalities). We hereby aim to improve and broaden the use of registered targeted therapy, whilst facilitating patient access to such therapy.
Plan of investigation: patients will be treated with approved targeted agents, selected based on results of a molecular profiling test of the patient's tumor. Eligible patients will have exhausted standard treatment options, and their tumor must harbor a potentially actionable molecular variant as defined in the protocol. The study will provide a tumor board to help physicians understand the profiling test results and treatment options, and will enable insights about the utility of this approach. In addition, next generation sequencing will be performed on fresh tumor biopsies for additional biomarker discovery. Patients from the Netherlands and the USA will be included in two similar though independent protocols (DRUP and TAPUR), allowing data-exchange and empowering of both trials.
Expected outcome: early signs of clinical activity of approved drugs outside their label, providing effective personalized treatment options, improved patient outcomes and access to targeted therapy.
9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.
This study's planned enrollment of 1,550 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →The Netherlands Cancer Institute is the lead sponsor of 224 studies on the registry; 66 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Patients must have acceptable organ function as defined below. However, specific inclusion/exclusion criteria specified in the drug-specific study manual will take precedence:
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:
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.
Exclusion Criteria:
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 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:
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.
Panitumumab for patients with a molecular tumor profile that can potentially be targeted by Panitumumab.
Drug: Panitumumab
Olaparib for patients with a molecular tumor profile that can potentially be targeted by Olaparib.
Drug: Olaparib
Dabrafenib for patients with a molecular tumor profile that can potentially be targeted by Dabrafenib.
Drug: Dabrafenib
Nilotinib for patients with a molecular tumor profile that can potentially be targeted by nilotinib.
Drug: Nilotinib
Trametinib for patients with a molecular tumor profile that can potentially be targeted by trametinib.
Drug: Trametinib
Erlotinib for patients with a molecular tumor profile that can potentially be targeted by erlotinib.
Drug: Erlotinib
Trastuzumab and Pertuzumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Trastuzumab and Pertuzumab.
Drug: Trastuzumab and Pertuzumab (combination treatment)
Vemurafenib and Cobimetinib (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Vemurafenib and Cobimetinib.
Drug: Vemurafenib and Cobimetinib (combination treatment)
Vismodegib for patients with a molecular tumor profile that can potentially be targeted by vismodegib.
Drug: Vismodegib
Regorafenib for patients with a molecular tumor profile that can potentially be targeted by regorafenib.
Drug: Regorafenib
Nivolumab for patients with a molecular tumor profile that can potentially be targeted by nivolumab.
Drug: Nivolumab
Afatinib for patients with a molecular tumor profile that can potentially be targeted by Afatinib.
Drug: Afatinib
Dabrafenib and trametinib (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Dabrafenib and trametinib.
Drug: Dabrafenib and trametinib
Ribociclib for patients with a molecular tumor profile that can potentially be targeted by Ribociclib.
Drug: Ribociclib
Lenvatinib for patients with a molecular tumor profile that can potentially be targeted by Lenvatinib.
Drug: Lenvatinib
Pembrolizumab for patients with a molecular tumor profile that can potentially be targeted by Pembrolizumab.
Drug: Pembrolizumab
Durvalumab for patients with a molecular tumor profile that can potentially be targeted by Durvalumab.
Drug: Durvalumab
Rucaparib for patients with a molecular tumor profile that can potentially be targeted by Rucaparib.
Drug: Rucaparib
Axitinib for patients with a molecular tumor profile that can potentially be targeted by Axitinib.
Drug: Axitinib
Palbociclib for patients with a molecular tumor profile that can potentially be targeted by Palbociclib.
Drug: Palbociclib
Crizotinib for patients with a molecular tumor profile that can potentially be targeted by Crizotinib.
Drug: Crizotinib
Sunitinib for patients with a molecular tumor profile that can potentially be targeted by Sunitinib.
Drug: Sunitinib
Cabozantinib for patients with a molecular tumor profile that can potentially be targeted by Cabozantinib.
Drug: Cabozantinib
Abemaciclib for patients with a molecular tumor profile that can potentially be targeted by Abemaciclib.
Drug: Abemaciclib
Alectinib for patients with a molecular tumor profile that can potentially be targeted by Alectinib.
Drug: Alectinib
Atezolizumab and bevacizumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Atezolizumab and bevacizumab.
Drug: Atezolizumab and Bevacizumab
Ipilimumab and nivolumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Ipilimumab and nivolumab.
Drug: Ipilimumab and nivolumab
Entrectinib for patients with a molecular tumor profile that can potentially be targeted by entrectinib.
Drug: Entrectinib
Talazoparib for patients with a molecular tumor profile that can potentially be targeted by talazoparib.
Drug: Talazoparib
Dacomitinib for patients with a molecular tumor profile that can potentially be targeted by dacomitinib.
Drug: Dacomitinib
Lorlatinib for patients with a molecular tumor profile that can potentially be targeted by lorlatinib.
Drug: Lorlatinib
Erdafitinib for patients with a molecular tumor profile that can potentially be targeted by erdafitinib.
Drug: Erdafitinib
Alpelisib for patients with a molecular tumor profile that can potentially be targeted by alpelisib.
Drug: Alpelisib
Niraparib for patients with a molecular tumor profile that can potentially be targeted by niraparib.
Drug: Niraparib
Pemigatinib for patients with a molecular tumor profile that can potentially be targeted by pemigatinib.
Drug: Pemigatinib
Selpercatinib for patients with a molecular tumor profile that can potentially be targeted by selpercatinib.
Drug: Selpercatinib
Tepotinib for patients with a molecular tumor profile that can potentially be targeted by tepotinib.
Drug: Tepotinib
Panitumumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of panitumumab might be expected based on their molecular tumor profile.
Also known as: Vectibix
Olaparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of olaparib might be expected based on their molecular tumor profile.
Also known as: Lynparza
Dabrafenib treatment for patients with an mutated advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of dabrafenib might be expected based on their molecular tumor profile.
Also known as: Tafinlar
Nilotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of nilotinib might be expected based on their molecular tumor profile.
Also known as: Tasigna
Trametinib treatment for patients with an mutated advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of trametinib might be expected based on their molecular tumor profile.
Also known as: Mekinist
Erlotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of erlotinib might be expected based on their molecular tumor profile.
Also known as: Tarceva
Trastuzumab and Pertuzumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of trastuzumab + pertuzumab might be expected based on their molecular tumor profile.
Also known as: Herceptin + Perjeta
Vemurafenib + Cobimetinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Vemurafenib + Cobimetinib might be expected based on their molecular tumor profile.
Also known as: Zelboraf + Cotellic
Vismodegib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of vismodegib might be expected based on their molecular tumor profile.
Also known as: Erivedge
Regorafenib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of vismodegib might be expected based on their molecular tumor profile.
Also known as: Stivarga
Nivolumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of nivolumab might be expected based on their molecular tumor profile.
Also known as: Opdivo
Afatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Afatinib might be expected based on their molecular tumor profile.
Also known as: Giotrif
Dabrafenib + trametinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Dabrafenib + Trametinib might be expected based on their molecular tumor profile.
Also known as: Tafinlar and Mekinist
Ribociclib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Ribociclib might be expected based on their molecular tumor profile.
Also known as: Kisqali
Lenvatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Lenvatinib might be expected based on their molecular tumor profile.
Also known as: Lenvima
Pembrolizumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Pembrolizumab might be expected based on their molecular tumor profile.
Also known as: Keytruda
Durvalumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Durvalumab might be expected based on their molecular tumor profile.
Also known as: MEDI4736
Rucaparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Rucaparib might be expected based on their molecular tumor profile.
Also known as: Rubraca
Axitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Axitinib might be expected based on their molecular tumor profile.
Also known as: Inlyta
Palbociclib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Palbociclib might be expected based on their molecular tumor profile.
Also known as: Ibrance
Crizotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Crizotinib might be expected based on their molecular tumor profile.
Also known as: Xalkori
Sunitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Sunitinib might be expected based on their molecular tumor profile.
Also known as: Sutent
Cabozantinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Cabozantinib might be expected based on their molecular tumor profile.
Also known as: Cabometyx
Abemaciclib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Abemaciclib might be expected based on their molecular tumor profile.
Also known as: Verzenios
Alectinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Alectinib might be expected based on their molecular tumor profile.
Also known as: Alecensa
Atezolizumab + Bevacizumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Atezolizumab + Bevacizumab might be expected based on their molecular tumor profile.
Also known as: Tecentriq and Avastin
Ipilimumab+nivolumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of ipilimimab + nivolumab might be expected based on their molecular tumor profile.
Also known as: Yervoy and Opdivo
Entrectinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of entrectinib might be expected based on their molecular tumor profile.
Also known as: Rozlytrek
Talazoparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of talazoparib might be expected based on their molecular tumor profile.
Also known as: Talzenna
Dacomitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of dacomitinib might be expected based on their molecular tumor profile.
Also known as: Vizimpro
Lorlatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of lorlatinib might be expected based on their molecular tumor profile.
Also known as: Lorviqua
Erdafitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of erdafitinib might be expected based on their molecular tumor profile.
Also known as: Balversa
Alpelisib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of alpelisib might be expected based on their molecular tumor profile.
Also known as: Piqray
Niraparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of niraparib might be expected based on their molecular tumor profile.
Also known as: Zejula
Pemigatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of pemigatinib might be expected based on their molecular tumor profile.
Also known as: Pemazyre
Selpercatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of selpercatinib might be expected based on their molecular tumor profile.
Also known as: Retsevmo
Tepotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of tepotinib might be expected based on their molecular tumor profile.
Also known as: Tepmetko
Percentage of patients that are treated based on their molecular tumor profile
Primary outcome measure 1 is the percentage of submitted patients, that can be treated based on their molecular tumor profile within the context of this protocol.
Time frame: 6 months after treatment initiation (estimated average)
Objective tumor response
Primary outcome measure 2 is the proportion of study participants with an objective tumor response upon study treatment..
Time frame: 6 months after treatment initiation (estimated average)
Stable disease
Primary outcome measure 3 is the proportion of study participants that has stable disease (SD) during study treatment.
Time frame: 6 months after treatment initiation (estimated average)
Treatment-related grade≥3 and serious adverse events
Primary outcome measure 4 is the proportion of patients that experience treatment-related grade≥3 and /or serious adverse events.
Time frame: 6 months after treatment initiation (estimated average)
Progression-free survival
Time frame: Up to 1 year after study completion
Overall survival
Time frame: Up to 1 year after study completion
Duration of treatment on study (time on drug)
Time frame: 6 months after treatment initiation (estimated average)
Concordance between pre-treatment and historic mutational tumor profile
Sequencing results of fresh pre-treatment biopsies will be available within 2 months after treatment initiation.
Time frame: 2 months after treatment initiation (estimated average)
Plan to share: No
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The Netherlands Cancer Institute