The Drug Rediscovery Protocol (DRUP Trial) (DRUP)

January 22, 2024 updated by: The Netherlands Cancer Institute

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

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.

Study Overview

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 Type

Interventional

Enrollment (Estimated)

1550

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: E.E. Voest, prof.
  • Phone Number: 0031205129111
  • Email: DRUP@nki.nl

Study Contact Backup

  • Name: K. Verkerk, MD
  • Phone Number: 0031205129111
  • Email: DRUP@nki.nl

Study Locations

      • Alkmaar, Netherlands
        • Recruiting
        • Noordwest ziekenhuisgroep Alkmaar (NWZ)
        • Contact:
          • M.P. Hendriks, MD, PhD
        • Principal Investigator:
          • M.P. Hendriks, MD, PhD
      • Almelo, Netherlands
        • Recruiting
        • Ziekenhuisgroep Twente
        • Contact:
          • E. Siemerink
        • Principal Investigator:
          • E. Siemerink
      • Amersfoort, Netherlands, 3818 ES
        • Recruiting
        • Meander Medisch Centrum
        • Principal Investigator:
          • G.A. Cirkel, MD
        • Contact:
          • G.A. Cirkel, MD
      • Amsterdam, Netherlands, 1066CX
        • Recruiting
        • Netherlands Cancer Institute
        • Contact:
          • E.E. Voest, prof.
          • Phone Number: 0031205129111
          • Email: DRUP@nki.nl
        • Contact:
          • K Verkerk, MD
          • Phone Number: 0031205129111
          • Email: DRUP@nki.nl
      • Amsterdam, Netherlands
        • Recruiting
        • Onze Lieve Vrouwe Gasthuis (OLVG)
        • Contact:
          • E.D. Kerver
        • Principal Investigator:
          • E.D. Kerver
      • Amsterdam, Netherlands, 1081 HV
        • Recruiting
        • Amsterdam UMC, locatie VUmc
        • Contact:
          • M Labots
        • Principal Investigator:
          • M Labots
      • Amsterdam, Netherlands, 1105AZ
        • Active, not recruiting
        • Amsterdam UMC, Locatie AMC
      • Apeldoorn, Netherlands
        • Recruiting
        • Gelre Ziekenhuizen
        • Contact:
          • S.C.S. Tromp
        • Principal Investigator:
          • S.C.S. Tromp
      • Arnhem, Netherlands
        • Recruiting
        • Rijnstate Ziekenhuis
        • Contact:
          • T. van Voorthuizen
        • Principal Investigator:
          • T. van Voorthuizen
      • Breda, Netherlands
        • Recruiting
        • Amphia Ziekenhuis
        • Contact:
          • H. Westgeest, MD, PhD
        • Principal Investigator:
          • H. Westgeest, MD, PhD
      • Delft, Netherlands
        • Recruiting
        • Reiner de Graaf Gasthuis
        • Principal Investigator:
          • A. Vulink
        • Contact:
          • A. Vulink
      • Den Haag, Netherlands
        • Recruiting
        • HAGA ziekenhuis
        • Contact:
          • D. Hautsma
        • Principal Investigator:
          • D. Hautsma
      • Den Haag, Netherlands
        • Recruiting
        • Haaglanden Medisch Centrum
        • Contact:
          • F. Jeurissen
        • Principal Investigator:
          • F. Jeurissen
      • Deventer, Netherlands
        • Recruiting
        • Deventer Ziekenhuis
        • Contact:
          • A. Imholz
        • Principal Investigator:
          • A. Imholz
      • Drachten, Netherlands
        • Recruiting
        • Nij Smellinghe Ziekenhuis
        • Contact:
          • S. Hovenga
        • Principal Investigator:
          • S. Hovenga
      • Ede, Netherlands
        • Recruiting
        • Ziekenhuis Gelderse Vallei
        • Contact:
          • P. de Mol
        • Principal Investigator:
          • P. de Mol
      • Eindhoven, Netherlands, 5631 BM
        • Recruiting
        • Maxima Medisch Centrum
        • Contact:
          • G Vreugdenhil, MD, PhD
        • Principal Investigator:
          • G Vreugdenhil, MD, PhD
      • Geleen, Netherlands, 6162 BG
        • Recruiting
        • Zuyderland Medisch Centrum
        • Contact:
          • F.L.G. Erdkamp, MD
        • Principal Investigator:
          • F.L.G. Erdkamp, MD
      • Gorinchem, Netherlands
        • Recruiting
        • Rivas zorggroep
        • Contact:
          • M.A. Davidis
        • Principal Investigator:
          • M.A. Davidis
      • Groningen, Netherlands
        • Recruiting
        • University Medical Center Groningen
        • Contact:
          • D.J.A. de Groot, MD, PhD
        • Principal Investigator:
          • D.J.A. de Groot, MD, PhD
      • Groningen, Netherlands
        • Recruiting
        • Martini Ziekenhuis
        • Contact:
          • J. van Rooijen
        • Principal Investigator:
          • J. van Rooijen
      • Haarlem, Netherlands
        • Recruiting
        • Spaarne Gasthuis
        • Contact:
          • G.J. de Klerk
        • Principal Investigator:
          • G.J. de Klerk
      • Hilversum, Netherlands
        • Not yet recruiting
        • Tergooi MC
        • Contact:
          • H.P. van den Berg
        • Principal Investigator:
          • H.P. van den Berg
      • Hoogeveen, Netherlands
        • Recruiting
        • Treant zorggroep
        • Contact:
          • C. Oldenhuis
        • Principal Investigator:
          • C. Oldenhuis
      • Leeuwarden, Netherlands
        • Recruiting
        • Medisch Centrum Leeuwaarden
        • Contact:
          • H. de Graaf
        • Principal Investigator:
          • H. de Graaf
      • Leiden, Netherlands
        • Recruiting
        • Leiden University Medical Center
        • Contact:
          • A.J. Gelderblom, MD, PhD
        • Principal Investigator:
          • A.J. Gelderblom, MD, PhD
      • Maastricht, Netherlands
        • Recruiting
        • Maastricht University Medical Center
        • Contact:
          • A. Hoeben, MD, PhD
        • Principal Investigator:
          • A. Hoeben, MD, PhD
      • NIjmegen, Netherlands, 6225GA
        • Recruiting
        • Radboud UMC
        • Contact:
          • C.M.L. van Herpen, MD, PhD
        • Principal Investigator:
          • C.M.L. van Herpen, MD, PhD
      • Nieuwegein, Netherlands
        • Recruiting
        • St. Antonius Ziekenhuis
        • Contact:
          • M. Los
        • Principal Investigator:
          • M. Los
      • Roosendaal, Netherlands
        • Recruiting
        • Bravis Ziekenhuis
        • Contact:
          • S. Boudewijns
        • Principal Investigator:
          • S. Boudewijns
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus MC
        • Contact:
          • M.J.A. de Jonge, MD, PhD
        • Principal Investigator:
          • M.J.A. de Jonge, MD, PhD
      • Rotterdam, Netherlands, 3045 PM
        • Recruiting
        • St. Fransicus Gasthuis
        • Contact:
          • A P Hamberg, MD
        • Principal Investigator:
          • A P Hamberg, MD
      • Tilburg, Netherlands, 5022 GC
        • Recruiting
        • Elisabeth-TweeSteden Ziekenhuis
        • Contact:
          • L.V. Beerepoot, MD, PhD
        • Principal Investigator:
          • L.V. Beerepoot, MD, PhD
      • Utrecht, Netherlands, 3584CX
        • Recruiting
        • University Medical Center Utrecht
        • Contact:
          • L.A. Devriese, MD, PhD
        • Principal Investigator:
          • L.A. Devriese, MD, PhD
      • Venlo, Netherlands
        • Recruiting
        • VieCuri Medisch Centrum
        • Contact:
          • Y. van der Wouw
        • Principal Investigator:
          • Y. van der Wouw
      • Zwolle, Netherlands
        • Recruiting
        • Isala Klinieken
        • Contact:
          • J.W.B. de Groot
        • Principal Investigator:
          • J.W.B. de Groot

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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.

  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 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).
  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 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).
  7. 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:

    1. 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)
    2. 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.

  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). 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.
  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Alectinib
Alectinib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Alecensa
Experimental: Axitinib
Axitinib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Inlyta
Experimental: Panitumumab
Panitumumab for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Vectibix
Experimental: Olaparib
Olaparib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Lynparza
Experimental: Dabrafenib
Dabrafenib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Tafinlar
Experimental: Nilotinib
Nilotinib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Tasigna
Experimental: Trametinib
Trametinib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Mekinist
Experimental: Erlotinib
Erlotinib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • 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.
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 Names:
  • 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.
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 Names:
  • Zelboraf + Cotellic
Experimental: Vismodegib
Vismodegib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Erivedge
Experimental: Regorafenib
Regorafenib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Stivarga
Experimental: Nivolumab
Nivolumab for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Opdivo
Experimental: Afatinib
Afatinib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • 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.
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 Names:
  • Tafinlar and Mekinist
Experimental: Ribociclib
Ribociclib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Kisqali
Experimental: Lenvatinib
Lenvatinib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Lenvima
Experimental: Pembrolizumab
Pembrolizumab for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Keytruda
Experimental: Durvalumab
Durvalumab for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • MEDI4736
Experimental: Rucaparib
Rucaparib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Rubraca
Experimental: Palbociclib
Palbociclib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Ibrance
Experimental: Crizotinib
Crizotinib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Xalkori
Experimental: Sunitinib
Sunitinib for patients with a molecular tumor profile that can potentially be targeted by 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 Names:
  • Sutent
Experimental: Cabozantinib
Cabozantinib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Cabometyx
Experimental: Abemaciclib
Abemaciclib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Verzenios
Experimental: Atezolizumab/bevacizumab
Atezolizumab and bevacizumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Tecentriq and Avastin
Experimental: Ipilimumab/nivolumab
Ipilimumab and nivolumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Yervoy and Opdivo
Experimental: Entrectinib
Entrectinib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Rozlytrek
Experimental: Talazoparib
Talazoparib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Talzenna
Experimental: dacomitinib
Dacomitinib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Vizimpro
Experimental: Lorlatinib
Lorlatinib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Lorviqua
Experimental: Erdafitinib
Erdafitinib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Balversa
Experimental: Alpelisib
Alpelisib for patients with a molecular tumor profile that can potentially be targeted by 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.
Other Names:
  • Piqray
Experimental: Niraparib
Niraparib for patients with a molecular tumor profile that can potentially be targeted by niraparib.
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.
Other Names:
  • Zejula
Experimental: Pemigatinib
Pemigatinib for patients with a molecular tumor profile that can potentially be targeted by pemigatinib.
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.
Other Names:
  • Pemazyre
Experimental: Selpercatinib
Selpercatinib for patients with a molecular tumor profile that can potentially be targeted by selpercatinib.
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.
Other Names:
  • Retsevmo
Experimental: Tepotinib
Tepotinib for patients with a molecular tumor profile that can potentially be targeted by tepotinib.
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.
Other Names:
  • Tepmetko

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months after treatment initiation (estimated average)
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..
6 months after treatment initiation (estimated average)
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.
6 months after treatment initiation (estimated average)
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.
6 months after treatment initiation (estimated average)

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
2 months after treatment initiation (estimated average)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2016

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

August 26, 2016

First Submitted That Met QC Criteria

October 4, 2016

First Posted (Estimated)

October 5, 2016

Study Record Updates

Last Update Posted (Actual)

January 24, 2024

Last Update Submitted That Met QC Criteria

January 22, 2024

Last Verified

January 1, 2024

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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