Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Drug Rediscovery Protocol (DRUP Trial) (DRUP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02925234
Recruitment Status : Unknown
Verified September 2016 by The Netherlands Cancer Institute.
Recruitment status was:  Recruiting
First Posted : October 5, 2016
Last Update Posted : October 5, 2016
Sponsor:
Collaborators:
Amgen
AstraZeneca
Bayer
Bristol-Myers Squibb
Novartis
Roche Pharma AG
Information provided by (Responsible Party):
The Netherlands Cancer Institute

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 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 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
Study Start Date : August 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: Panitumumab
Panitumumab for patients with KRAS-BRAF-NRAS wild-type tumors for whom anti-tumor activity of panitumumab might be expected.
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 BRCA or ATM mutated tumors for whom anti-tumor activity of olaparib might be expected.
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 BRAF mutated tumors for whom anti-tumor activity of dabrafenib might be expected.
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 HER2 overexpressing, amplified or mutated tumor for whom anti-tumor activity of Trastuzumab + Pertuzumab might be expected.
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 BRAF mutated tumor for whom anti-tumor activity of vemurafenib + cobimetinib might be expected.
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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02925234


Contacts
Layout table for location contacts
Contact: E.E. Voest, prof. 0031205129111 DRUP@nki.nl
Contact: D.L. vd Velden, MD 0031205129111 DRUP@nki.nl

Locations
Layout table for location information
Netherlands
Meander Medical Center Not yet recruiting
Amersfoort, Utrecht, Netherlands, 3818 ES
Contact: H.J. Bloemendal, MD, PhD         
Principal Investigator: H.J. Bloemendal, MD, PhD         
Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066CX
Contact: E.E. Voest, prof.    0031205129111    DRUP@nki.nl   
Contact: D.L. vd Velden, MD    0031205129111    DRUP@nki.nl   
AZVU Not yet recruiting
Amsterdam, Netherlands, 1081 HV
Contact: H Verheul, prof         
Principal Investigator: H Verheul, prof         
Amphia Hospital Not yet recruiting
Breda, Netherlands
Contact: A.J. Ten Tije, MD, PhD         
Principal Investigator: A.J. Ten Tije, MD, PhD         
Maxima Medisch Centrum Not yet recruiting
Eindhoven, Netherlands, 5631 BM
Contact: G Vreugdenhil, MD, PhD         
Principal Investigator: G Vreugdenhil, MD, PhD         
Orbis Concern Not yet recruiting
Geleen, Netherlands, 6162 BG
Contact: F L Erdkamp, MD         
Principal Investigator: F L Erdkamp, MD         
University Medical Center Groningen Not yet recruiting
Groningen, Netherlands
Contact: D.J.A. de Groot, MD, PhD         
Principal Investigator: D.J.A. de Groot, MD, PhD         
Leiden University Medical Center Not yet recruiting
Leiden, Netherlands
Contact: A.J. Gelderblom, MD, PhD         
Principal Investigator: A.J. Gelderblom, MD, PhD         
Maastricht University Medical Center Not yet recruiting
Maastricht, Netherlands
Contact: A. Hoeben, MD, PhD         
Principal Investigator: A. Hoeben, MD, PhD         
Radboud umc Not yet recruiting
NIjmegen, Netherlands, 6225GA
Contact: C.M.L. van Herpen, MD, PhD         
Principal Investigator: C.M.L. van Herpen, MD, PhD         
St. Fransicus Gasthuis Not yet recruiting
Rotterdam, Netherlands, 3045 PM
Contact: A P Hamberg, MD         
Principal Investigator: A P Hamberg, MD         
Erasmus MC Not yet recruiting
Rotterdam, Netherlands
Contact: M.J.A. de Jonge, MD, PhD         
Principal Investigator: M.J.A. de Jonge, MD, PhD         
St. Elisabeth Not yet recruiting
Tilburg, Netherlands, 5022 GC
Contact: L.V. Beerepoot, MD, PhD         
Principal Investigator: L.V. Beerepoot, MD, PhD         
University Medical Center Utrecht Not yet recruiting
Utrecht, Netherlands, 3584CX
Contact: M.H.G. Langenberg, MD, PhD         
Principal Investigator: M.H.G. Langenberg, MD, PhD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Amgen
AstraZeneca
Bayer
Bristol-Myers Squibb
Novartis
Roche Pharma AG
Investigators
Layout table for investigator information
Principal Investigator: E.E. Voest, prof. The Netherlands Cancer Institute

Layout table for additonal information
Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02925234     History of Changes
Other Study ID Numbers: M15DRU
First Posted: October 5, 2016    Key Record Dates
Last Update Posted: October 5, 2016
Last Verified: September 2016
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:
Layout table for MeSH terms
Neoplasms
Nivolumab
Trastuzumab
Panitumumab
Pertuzumab
Erlotinib Hydrochloride
Olaparib
Trametinib
Vemurafenib
Dabrafenib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors