The Drug Rediscovery Protocol (DRUP Trial)

NCT02925234

Last updated date
Study Location
Noordwesr ziekenhuis Alkmaar (NWZ)
Alkmaar, , , Netherlands
Contact
0031205129111

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

0031205129111

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Cancer, Tumors, Neoplasm, Neoplasia
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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.

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

TRY A NEW SEARCH

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.

Based on your search, you may also be interested in

Cancer, Tumors, Neoplasm, NeoplasiaThe Drug Rediscovery Protocol (DRUP Trial)
NCT02925234
  1. Alkmaar,
  2. Amsterdam,
  3. Amsterdam,
  4. Amersfoort, Utrecht
  5. Amsterdam,
  6. Breda,
  7. Eindhoven,
  8. Geleen,
  9. Groningen,
  10. Leiden,
  11. Maastricht,
  12. NIjmegen,
  13. Rotterdam,
  14. Rotterdam,
  15. Tilburg,
  16. Utrecht,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE The Drug Rediscovery Protocol (DRUP Trial)
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer
  • Tumors
  • Neoplasm
  • Neoplasia
Intervention  ICMJE
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
  • Drug: Brigatinib
    Brigatinib 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 Brigatinib might be expected based on their molecular tumor profile.
    Other Name: Alunbrig
  • 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.
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: Panitumumab
    Panitumumab for patients with a molecular tumor profile that can potentially be targeted by Panitumumab.
    Intervention: Drug: Panitumumab
  • Experimental: Olaparib
    Olaparib for patients with a molecular tumor profile that can potentially be targeted by Olaparib.
    Intervention: Drug: Olaparib
  • Experimental: Dabrafenib
    Dabrafenib for patients with a molecular tumor profile that can potentially be targeted by Dabrafenib.
    Intervention: Drug: Dabrafenib
  • Experimental: Nilotinib
    Nilotinib for patients with a molecular tumor profile that can potentially be targeted by nilotinib.
    Intervention: Drug: Nilotinib
  • Experimental: Trametinib
    Trametinib for patients with a molecular tumor profile that can potentially be targeted by trametinib.
    Intervention: Drug: Trametinib
  • Experimental: Erlotinib
    Erlotinib for patients with a molecular tumor profile that can potentially be targeted by erlotinib.
    Intervention: Drug: Erlotinib
  • 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.
    Intervention: Drug: Trastuzumab and Pertuzumab (combination treatment)
  • 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.
    Intervention: Drug: Vemurafenib and Cobimetinib (combination treatment)
  • Experimental: Vismodegib
    Vismodegib for patients with a molecular tumor profile that can potentially be targeted by vismodegib.
    Intervention: Drug: Vismodegib
  • Experimental: Regorafenib
    Regorafenib for patients with a molecular tumor profile that can potentially be targeted by regorafenib.
    Intervention: Drug: Regorafenib
  • Experimental: Nivolumab
    Nivolumab for patients with a molecular tumor profile that can potentially be targeted by nivolumab.
    Intervention: Drug: Nivolumab
  • Experimental: Afatinib
    Afatinib for patients with a molecular tumor profile that can potentially be targeted by Afatinib.
    Intervention: Drug: Afatinib
  • 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.
    Intervention: Drug: Dabrafenib and trametinib
  • Experimental: Ribociclib
    Ribociclib for patients with a molecular tumor profile that can potentially be targeted by Ribociclib.
    Intervention: Drug: Ribociclib
  • Experimental: Lenvatinib
    Lenvatinib for patients with a molecular tumor profile that can potentially be targeted by Lenvatinib.
    Intervention: Drug: Lenvatinib
  • Experimental: Pembrolizumab
    Pembrolizumab for patients with a molecular tumor profile that can potentially be targeted by Pembrolizumab.
    Intervention: Drug: Pembrolizumab
  • Experimental: Durvalumab
    Durvalumab for patients with a molecular tumor profile that can potentially be targeted by Durvalumab.
    Intervention: Drug: Durvalumab
  • Experimental: Rucaparib
    Rucaparib for patients with a molecular tumor profile that can potentially be targeted by Rucaparib.
    Intervention: Drug: Rucaparib
  • Experimental: Axitinib
    Axitinib for patients with a molecular tumor profile that can potentially be targeted by Axitinib.
    Intervention: Drug: Axitinib
  • Experimental: Palbociclib
    Palbociclib for patients with a molecular tumor profile that can potentially be targeted by Palbociclib.
    Intervention: Drug: Palbociclib
  • Experimental: Crizotinib
    Crizotinib for patients with a molecular tumor profile that can potentially be targeted by Crizotinib.
    Intervention: Drug: Crizotinib
  • Experimental: Sunitinib
    Sunitinib for patients with a molecular tumor profile that can potentially be targeted by Sunitinib.
    Intervention: Drug: Sunitinib
  • Experimental: Cabozantinib
    Cabozantinib for patients with a molecular tumor profile that can potentially be targeted by Cabozantinib.
    Intervention: Drug: Cabozantinib
  • Experimental: Brigatinib
    Brigatinib for patients with a molecular tumor profile that can potentially be targeted by Brigatinib.
    Intervention: Drug: Brigatinib
  • Experimental: Abemaciclib
    Abemaciclib for patients with a molecular tumor profile that can potentially be targeted by Abemaciclib.
    Intervention: Drug: Abemaciclib
  • Experimental: Alectinib
    Alectinib for patients with a molecular tumor profile that can potentially be targeted by Alectinib.
    Intervention: Drug: Alectinib
  • Experimental: Atezolizumab/bevacizumab
    Atezolizumab and bevacizumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Atezolizumab and bevacizumab.
    Intervention: Drug: Atezolizumab and Bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 13, 2020)
950
Original Estimated Enrollment  ICMJE
 (submitted: October 4, 2016)
400
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: E.E. Voest, prof.0031205129111[email protected].nl
Contact: D.L. vd Velden, MD0031205129111[email protected]
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02925234
Other Study ID Numbers  ICMJE M15DRU
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party The Netherlands Cancer Institute
Study Sponsor  ICMJE The Netherlands Cancer Institute
Collaborators  ICMJE
  • Amgen
  • AstraZeneca
  • Bayer
  • Bristol-Myers Squibb
  • Novartis
  • Roche Pharma AG
  • Merck Sharp & Dohme Corp.
  • Boehringer Ingelheim
  • Ipsen
  • Eisai Inc.
  • Pfizer
  • Clovis Oncology, Inc.
Investigators  ICMJE
Principal Investigator:E.E. Voest, prof.The Netherlands Cancer Institute
PRS Account The Netherlands Cancer Institute
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP