The Drug Rediscovery Protocol (DRUP Trial) (DRUP)

• ClinicalTrials.gov Identifier: NCT02925234
• Recruitment Status: Recruiting
• First Posted: October 5, 2016
• Last Update Posted: February 13, 2023
• Sponsor: The Netherlands Cancer Institute
• Collaborators: Amgen; AstraZeneca; Bayer; Bristol-Myers Squibb; Novartis; Roche Pharma AG; Merck Sharp & Dohme LLC; Boehringer Ingelheim; Ipsen; Eisai Inc.; Pfizer; Clovis Oncology, Inc.; Eli Lilly and Company; Janssen, LP
• Information provided by (Responsible Party): The Netherlands Cancer Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cancer; Tumors; Neoplasm; Neoplasia	Drug: Panitumumab; Drug: Olaparib; Drug: Dabrafenib; Drug: Nilotinib; Drug: Trametinib; Drug: Erlotinib; Drug: Trastuzumab and Pertuzumab (combination treatment); Drug: Vemurafenib and Cobimetinib (combination treatment); Drug: Vismodegib; Drug: Regorafenib; Drug: Nivolumab; Drug: Afatinib; Drug: Dabrafenib and trametinib; Drug: Ribociclib; Drug: Lenvatinib; Drug: Pembrolizumab; Drug: Durvalumab; Drug: Rucaparib; Drug: Axitinib; Drug: Palbociclib; Drug: Crizotinib; Drug: Sunitinib; Drug: Cabozantinib; Drug: Abemaciclib; Drug: Alectinib; Drug: Atezolizumab and Bevacizumab; Drug: Ipilimumab and nivolumab; Drug: Entrectinib; Drug: Talazoparib; Drug: Dacomitinib; Drug: Lorlatinib; Drug: Erdafitinib; Drug: Alpelisib	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1550 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Dutch National Study on Behalf of the CPCT to Facilitate Patient Access to Commercially Available, Targeted Anti-cancer Drugs to Determine the Potential Efficacy in Treatment of Advanced Cancers With a Known Molecular Profile
• Actual Study Start Date: August 2016
• Estimated Primary Completion Date: September 2027
• Estimated Study Completion Date: December 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Panitumumab; Panitumumab for patients with a molecular tumor profile that can potentially be targeted by Panitumumab.	Drug: Panitumumab; 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.; Other Name: Vectibix
Experimental: Olaparib; Olaparib for patients with a molecular tumor profile that can potentially be targeted by Olaparib.	Drug: Olaparib; 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.; Other Name: Lynparza
Experimental: Dabrafenib; Dabrafenib for patients with a molecular tumor profile that can potentially be targeted by Dabrafenib.	Drug: Dabrafenib; 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.; Other Name: Tafinlar
Experimental: Nilotinib; Nilotinib for patients with a molecular tumor profile that can potentially be targeted by nilotinib.	Drug: Nilotinib; 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.; Other Name: Tasigna
Experimental: Trametinib; Trametinib for patients with a molecular tumor profile that can potentially be targeted by trametinib.	Drug: Trametinib; 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.; Other Name: Mekinist
Experimental: Erlotinib; Erlotinib for patients with a molecular tumor profile that can potentially be targeted by erlotinib.	Drug: Erlotinib; 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.; Other Name: Tarceva
Experimental: Trastuzumab & Pertuzumab (combination); 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); 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.; Other Name: Herceptin + Perjeta
Experimental: Vemurafenib & Cobimetinib (combination); 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); 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.; Other Name: Zelboraf + Cotellic
Experimental: Vismodegib; Vismodegib for patients with a molecular tumor profile that can potentially be targeted by vismodegib.	Drug: Vismodegib; 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.; Other Name: Erivedge
Experimental: Regorafenib; Regorafenib for patients with a molecular tumor profile that can potentially be targeted by regorafenib.	Drug: Regorafenib; 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.; Other Name: Stivarga
Experimental: Nivolumab; Nivolumab for patients with a molecular tumor profile that can potentially be targeted by nivolumab.	Drug: Nivolumab; 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.; Other Name: Opdivo
Experimental: Afatinib; Afatinib for patients with a molecular tumor profile that can potentially be targeted by Afatinib.	Drug: Afatinib; 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.; Other Name: Giotrif
Experimental: Dabrafenib & trametinib (combination); 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; 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.; Other Name: Tafinlar and Mekinist
Experimental: Ribociclib; Ribociclib for patients with a molecular tumor profile that can potentially be targeted by Ribociclib.	Drug: Ribociclib; 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.; Other Name: Kisqali
Experimental: Lenvatinib; Lenvatinib for patients with a molecular tumor profile that can potentially be targeted by Lenvatinib.	Drug: Lenvatinib; 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.; Other Name: Lenvima
Experimental: Pembrolizumab; Pembrolizumab for patients with a molecular tumor profile that can potentially be targeted by Pembrolizumab.	Drug: Pembrolizumab; 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.; Other Name: Keytruda
Experimental: Durvalumab; Durvalumab for patients with a molecular tumor profile that can potentially be targeted by Durvalumab.	Drug: Durvalumab; 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.; Other Name: MEDI4736
Experimental: Rucaparib; Rucaparib for patients with a molecular tumor profile that can potentially be targeted by Rucaparib.	Drug: Rucaparib; 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.; Other Name: Rubraca
Experimental: Axitinib; Axitinib for patients with a molecular tumor profile that can potentially be targeted by Axitinib.	Drug: Axitinib; 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.; Other Name: Inlyta
Experimental: Palbociclib; Palbociclib for patients with a molecular tumor profile that can potentially be targeted by Palbociclib.	Drug: Palbociclib; 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.; Other Name: Ibrance
Experimental: Crizotinib; Crizotinib for patients with a molecular tumor profile that can potentially be targeted by Crizotinib.	Drug: Crizotinib; 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.; Other Name: Xalkori
Experimental: Sunitinib; Sunitinib for patients with a molecular tumor profile that can potentially be targeted by Sunitinib.	Drug: Sunitinib; 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.; Other Name: Sutent
Experimental: Cabozantinib; Cabozantinib for patients with a molecular tumor profile that can potentially be targeted by Cabozantinib.	Drug: Cabozantinib; 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.
Experimental: Abemaciclib; Abemaciclib for patients with a molecular tumor profile that can potentially be targeted by Abemaciclib.	Drug: Abemaciclib; 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.
Experimental: Alectinib; Alectinib for patients with a molecular tumor profile that can potentially be targeted by Alectinib.	Drug: Alectinib; 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.
Experimental: Atezolizumab/bevacizumab; 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; 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.
Experimental: Ipilimumab/nivolumab; 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; 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.
Experimental: Entrectinib; Entrectinib for patients with a molecular tumor profile that can potentially be targeted by entrectinib.	Drug: Entrectinib; 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.
Experimental: Talazoparib; Talazoparib for patients with a molecular tumor profile that can potentially be targeted by talazoparib.	Drug: Talazoparib; 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.
Experimental: dacomitinib; Dacomitinib for patients with a molecular tumor profile that can potentially be targeted by dacomitinib.	Drug: Dacomitinib; 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.
Experimental: Lorlatinib; Lorlatinib for patients with a molecular tumor profile that can potentially be targeted by lorlatinib.	Drug: Lorlatinib; 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.
Experimental: Erdafitinib; Erdafitinib for patients with a molecular tumor profile that can potentially be targeted by erdafitinib.	Drug: Erdafitinib; 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.
Experimental: Alpelisib; Alpelisib for patients with a molecular tumor profile that can potentially be targeted by alpelisib.	Drug: Alpelisib; 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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients that are treated based on their molecular tumor profile [ Time Frame: 6 months after treatment initiation (estimated average) ]
   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.
2. Objective tumor response [ Time Frame: 6 months after treatment initiation (estimated average) ]
   Primary outcome measure 2 is the proportion of study participants with an objective tumor response upon study treatment..
3. Stable disease [ Time Frame: 6 months after treatment initiation (estimated average) ]
   Primary outcome measure 3 is the proportion of study participants that has stable disease (SD) during study treatment.
4. Treatment-related grade≥3 and serious adverse events [ Time Frame: 6 months after treatment initiation (estimated average) ]
   Primary outcome measure 4 is the proportion of patients that experience treatment-related grade≥3 and /or serious adverse events.

Secondary Outcome Measures :

1. Progression-free survival [ Time Frame: Up to 1 year after study completion ]
2. Overall survival [ Time Frame: Up to 1 year after study completion ]
3. Duration of treatment on study (time on drug) [ Time Frame: 6 months after treatment initiation (estimated average) ]

Other Outcome Measures:

1. Concordance between pre-treatment and historic mutational tumor profile [ Time Frame: 2 months after treatment initiation (estimated average) ]
   Sequencing results of fresh pre-treatment biopsies will be available within 2 months after treatment initiation.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Contacts

Contact: E.E. Voest, prof.; 0031205129111; DRUP@nki.nl

Contact: D.L. vd Velden, MD; 0031205129111; DRUP@nki.nl

Locations

Netherlands

Meander Medical Center; Recruiting

Amersfoort, Utrecht, Netherlands, 3818 ES

Contact: H.J. Bloemendal, MD

Principal Investigator: G.A. Cirkel, MD

Noordwesr ziekenhuis Alkmaar (NWZ); Recruiting

Alkmaar, Netherlands

Contact: M.P. Hendriks, MD, PhD

Principal Investigator: M.P. Hendriks, MD, PhD

Ziekehuisgroep Twente; Recruiting

Almelo, Netherlands

Contact: Siemerik

Principal Investigator: Siemerik

Netherlands Cancer Institute; Recruiting

Amsterdam, Netherlands, 1066CX

Contact: E.E. Voest, prof. 0031205129111 DRUP@nki.nl

Contact: L. Zeverijn, MD 0031205129111 DRUP@nki.nl

VUMC; Recruiting

Amsterdam, Netherlands, 1081 HV

Contact: M Labots

Principal Investigator: M Labots

Amsterdam UMC; Recruiting

Amsterdam, Netherlands, 1105AZ

Contact: Adriaan Bins, MD, PhD a.d.bins@amc.uva.nl

Principal Investigator: A Bins, MD, PhD

Onze Lieve Vrouwe Gasthuis (OLVG); Recruiting

Amsterdam, Netherlands

Contact: E.D. Kerver

Principal Investigator: E.D. Kerver

Gelre ziekehuizen; Recruiting

Apeldoorn, Netherlands

Contact: S.C.S. Tromp

Principal Investigator: S.C.S. Tromp

Rijnstate; Recruiting

Arnhem, Netherlands

Contact: van Voorthuizen

Principal Investigator: van Voorthuizen

Amphia Hospital; Recruiting

Breda, Netherlands

Contact: H. Westgeest, MD, PhD

Principal Investigator: H. Westgeest, MD, PhD

Reiner de Graaf Gasthuis; Recruiting

Delft, Netherlands

Contact: V.O. Dezentje

Principal Investigator: V.O. Dezentje

Haaglanden medisch centrum; Recruiting

Den Haag, Netherlands

Contact: Jeurissen

Principal Investigator: Jeurissen

Haga ziekehuis; Recruiting

Den Haag, Netherlands

Contact: Hautsma

Principal Investigator: Hautsma

Deventer ziekenhuis; Recruiting

Deventer, Netherlands

Contact: Imholz

Principal Investigator: Imholz

Ziekehuis Nij Smellinghe; Recruiting

Drachten, Netherlands

Contact: Hovenga

Principal Investigator: Hovenga

Ziekehuis Gelderse Vallei; Recruiting

Ede, Netherlands

Contact: de Mol

Principal Investigator: dr Mol

Maxima Medisch Centrum; Recruiting

Eindhoven, Netherlands, 5631 BM

Contact: G Vreugdenhil, MD, PhD

Principal Investigator: G Vreugdenhil, MD, PhD

Orbis Concern; Recruiting

Geleen, Netherlands, 6162 BG

Contact: F L Erdkamp, MD

Principal Investigator: F L Erdkamp, MD

Rivas zorggroep; Recruiting

Gorinchem, Netherlands

Contact: M.A. Davidis

Principal Investigator: M.A. Davidis

Martini; Recruiting

Groningen, Netherlands

Contact: van Rooijen

Principal Investigator: van Rooijen

University Medical Center Groningen; Recruiting

Groningen, Netherlands

Contact: D.J.A. de Groot, MD, PhD

Principal Investigator: D.J.A. de Groot, MD, PhD

Spaarne gasthuis; Recruiting

Haarlem, Netherlands

Contact: G.J. de Klerk

Principal Investigator: G.J. de Klerk

Treant zorggroep; Recruiting

Hoogeveen, Netherlands

Contact: Oldenhuis

Principal Investigator: Oldenhuis

Medisch Centrum Leeuwaarden; Recruiting

Leeuwarden, Netherlands

Contact: de Graaf

Principal Investigator: de Graaf

Leiden University Medical Center; Recruiting

Leiden, Netherlands

Contact: A.J. Gelderblom, MD, PhD

Principal Investigator: A.J. Gelderblom, MD, PhD

Maastricht University Medical Center; Recruiting

Maastricht, Netherlands

Contact: A. Hoeben, MD, PhD

Principal Investigator: A. Hoeben, MD, PhD

St. Antonius ziekhuis; Recruiting

Nieuwegein, Netherlands

Contact: Los

Principal Investigator: Los

Radboud umc; Recruiting

NIjmegen, Netherlands, 6225GA

Contact: C.M.L. van Herpen, MD, PhD

Principal Investigator: H Verheul, MD, PhD

Bravis; Recruiting

Roosendaal, Netherlands

Contact: Boudewijn

Principal Investigator: Boudewijn

St. Fransicus Gasthuis; Recruiting

Rotterdam, Netherlands, 3045 PM

Contact: A P Hamberg, MD

Principal Investigator: A P Hamberg, MD

Erasmus MC; Recruiting

Rotterdam, Netherlands

Contact: M.J.A. de Jonge, MD, PhD

Principal Investigator: M.J.A. de Jonge, MD, PhD

St. Elisabeth; Recruiting

Tilburg, Netherlands, 5022 GC

Contact: L.V. Beerepoot, MD, PhD

Principal Investigator: L.V. Beerepoot, MD, PhD

University Medical Center Utrecht; Recruiting

Utrecht, Netherlands, 3584CX

Contact: M.H.G. Langenberg, MD, PhD

Principal Investigator: L Devriese, MD, PhD

Viecuri; Recruiting

Venray, Netherlands

Contact: van der wouw

Principal Investigator: van der Wouw

Isala; Recruiting

Zwolle, Netherlands

Contact: de Groot

Principal Investigator: de Groot

Sponsors and Collaborators

The Netherlands Cancer Institute

Amgen

AstraZeneca

Bayer

Bristol-Myers Squibb

Novartis

Roche Pharma AG

Merck Sharp & Dohme LLC

Boehringer Ingelheim

Ipsen

Eisai Inc.

Pfizer

Clovis Oncology, Inc.

Eli Lilly and Company

Janssen, LP

Investigators

• Principal Investigator: E.E. Voest, prof.; The Netherlands Cancer Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

van Berge Henegouwen JM, van der Wijngaart H, Zeverijn LJ, Hoes LR, Meertens M, Huitema ADR, Devriese LA, Labots M, Verheul HMW, Voest EE, Gelderblom H. Efficacy and toxicity of vemurafenib and cobimetinib in relation to plasma concentrations, after administration via feeding tube in patients with BRAF-mutated thyroid cancer: a case series and review of literature. Cancer Chemother Pharmacol. 2022 Jul;90(1):97-104. doi: 10.1007/s00280-022-04437-z. Epub 2022 May 22.

Nakauma-Gonzalez JA, Rijnders M, van Riet J, van der Heijden MS, Voortman J, Cuppen E, Mehra N, van Wilpe S, Oosting SF, Rijstenberg LL, Westgeest HM, Zwarthoff EC, de Wit R, van der Veldt AAM, van de Werken HJG, Lolkema MPJ, Boormans JL. Comprehensive Molecular Characterization Reveals Genomic and Transcriptomic Subtypes of Metastatic Urothelial Carcinoma. Eur Urol. 2022 Apr;81(4):331-336. doi: 10.1016/j.eururo.2022.01.026. Epub 2022 Jan 25.

• Responsible Party: The Netherlands Cancer Institute
• ClinicalTrials.gov Identifier: NCT02925234
• Other Study ID Numbers: M15DRU
• First Posted: October 5, 2016
• Last Update Posted: February 13, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by The Netherlands Cancer Institute:

Molecular tumor profile; Multidisciplinary tumor board; Antitumor drugs; Molecular Targeted Therapy; Drug Repositioning; Off-Label Use; Sequence Analysis, DNA

Additional relevant MeSH terms:

Neoplasms; Bevacizumab; Pembrolizumab; Nivolumab; Trastuzumab; Ipilimumab; Atezolizumab; Durvalumab; Pertuzumab; Panitumumab; Sunitinib; Lenvatinib; Olaparib; Palbociclib; Trametinib; Axitinib; Afatinib; Vemurafenib; Dabrafenib; Crizotinib; Talazoparib; Rucaparib; Entrectinib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors