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ProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling (ProTarget)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04341181
Recruitment Status : Recruiting
First Posted : April 10, 2020
Last Update Posted : September 25, 2020
Sponsor:
Collaborators:
Roche Pharma AG
Pfizer
GlaxoSmithKline
Information provided by (Responsible Party):
Ulrik Lassen, Rigshospitalet, Denmark

Brief Summary:

The ProTarget study is a phase II, prospective, non-randomized clinical trial with the primary purpose of investigating the safety and efficacy of commercially available cancer drugs that target specific changes in cancer cell DNA to treat patients with advanced cancer. The primary endpoint is anti-tumor activity or stable disease documented after 16 weeks of experimental drug treatment. The drugs used in the trial have been approved by EMA/FDA for the treatment of certain cancers. Choice of drug is based on whether the patient's cancer cells contain precisely the DNA change (i) targeted by the EMA/FDA-approved drug or (ii) related to sensitivity to the EMA/FDA-approved drug. The trial drug is thus not approved by the EMA/FDA or in Denmark for the treatment of the patient's cancer - it is so-called "off-label use". The secondary purposes are:

  • To detect side effects in patients treated with commercially available targeted cancer drugs.
  • Performing biomarker analyzes, including (but not limited to) whole-genome analysis (WGS) on a fresh tumor tissue sample (biopsy) at baseline and progression.
  • To investigate mechanisms of resistance using recurrent / serial fresh tumor biopsies for WGS and so-called liquid biopsies, which are blood samples in which the cancer cell DNA is analyzed.

The secondary endpoints include response duration, progression-free survival, and overall survival.


Condition or disease Intervention/treatment Phase
Cancer Tumors Neoplasms Neoplasia Drug: Alectinib Drug: Atezolizumab Drug: Avelumab Drug: Axitinib Drug: Erlotinib Drug: Vemurafenib plus Cobimetinib (combination) Drug: Trastuzumab plus Pertuzumab (combination) Drug: Trastuzumab emtansine Drug: Vismodegib Drug: Niraparib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling
Actual Study Start Date : August 24, 2020
Estimated Primary Completion Date : April 30, 2024
Estimated Study Completion Date : April 30, 2025

Arm Intervention/treatment
Experimental: Alectinib
Alectinib for patients with a molecular tumor profile that can potentially be targeted by Alectinib.
Drug: Alectinib
Alectinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Alectinib might be expected based on their molecular tumor profile.
Other Name: Alecensa

Experimental: Atezolizumab
Atezolizumab for patients with a molecular tumor profile that can potentially be targeted by Atezolizumab.
Drug: Atezolizumab
Atezolizumab 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 might be expected based on their molecular tumor profile.
Other Name: Tecentriq

Experimental: Avelumab
Avelumab for patients with a molecular tumor profile that can potentially be targeted by Avelumab.
Drug: Avelumab
Avelumab 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 Avelumab might be expected based on their molecular tumor profile.
Other Name: Bavencio

Experimental: Axitinib
Axitinib for patients with a molecular tumor profile that can potentially be targeted by Axitinib.
Drug: Axitinib
Axitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Axitinib might be expected based on their molecular tumor profile.
Other Name: Inlyta

Experimental: 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: Vemurafenib plus Cobimetinib (combination)
Vemurafenib plus Cobimetinib (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Vemurafenib plus Cobimetinib.
Drug: Vemurafenib plus Cobimetinib (combination)
Vemurafenib plus 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 plus Cobimetinib might be expected based on their molecular tumor profile.
Other Name: Zelboraf plus Cotellic (combination)

Experimental: Trastuzumab plus Pertuzumab (combination)
Trastuzumab plus Pertuzumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Trastuzumab plus Pertuzumab.
Drug: Trastuzumab plus Pertuzumab (combination)
Trastuzumab plus 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 plus Pertuzumab might be expected based on their molecular tumor profile.
Other Name: Herceptin plus Perjeta (combination)

Experimental: Trastuzumab emtansin
Trastuzumab emtansin for patients with a molecular tumor profile that can potentially be targeted by Trastuzumab emtansin.
Drug: Trastuzumab emtansine
Trastuzumab emtansine 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 emtansine might be expected based on their molecular tumor profile.
Other Name: Kadcyla

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: Niraparib
Niraparib for patients with a molecular tumor profile that can potentially be targeted by Niraparib.
Drug: 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 Name: Zejula




Primary Outcome Measures :
  1. Response rate [ Time Frame: 16 weeks ]
    Response according to RECIST



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.


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

Inclusion Criteria:

  1. Patient (age≥ 18 years) with a histologically-proven locally advanced or metastatic malignant disease who is no longer benefitting from standard anti-cancer treatment or for whom, in the opinion of the investigator, no such treatment is available or indicated.
  2. ECOG performance status 0-2
  3. Patients must have acceptable organ function as defined below. However, as noted above, drug-specific inclusion/exclusion criteria specified in the appendix for each agent will take precedence for this and all inclusion criteria:

    1. Absolute neutrophil count ≥ 1500 µl
    2. Hemoglobin > 5.6 mmol/l
    3. Platelets > 75,000/µl
    4. Total bilirubin < 1.5 x institutional upper limit of normal (ULN)
    5. AST (SGOT) and ALT(SGPT) < 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with known hepatic metastases)
    6. Calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2.
  4. Patients must have measurable or evaluable disease (per RECIST v1.1 for solid tumor), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable disease by physical or radiographic examination but do not meet these definitions of measurable disease are eligible and will be considered to have evaluable disease. Patient's whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumor marker only) are NOT eligible, with the exception of CA-125 for ovarian cancer and PSA for prostate cancer.
  5. Results must be available from a genomic test or immunohistochemistry (IHC) test for protein expression performed in a laboratory accredited by the competent local regulatory authority. The genomic or IHC test used to qualify a patient for participation in ProTarget may have been performed on any specimen of the patient's tumor obtained at any point during the patient's care at the discretion of the patient's treating physician. Genomic assays performed on cell-free DNA in plasma ("liquid biopsies") will also be acceptable if the genomic analysis is performed in a laboratory accredited by the competent local regulatory authority.

    A new biopsy must be performed if possible, for central confirmation by WGS (the result may be awaited and is not required before first dosing).

    Note: Eligible genomic 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), whole exome sequencing (WES). The test may have been performed on a fresh (frozen or in RNA-later) or paraffin-embedded specimen of the primary tumor or a metastatic deposit or on cell free DNA derived from plasma, as determined by the treating physician, and must reveal a potentially actionable genomic variant as defined in Section 5.0, or protein overexpression by IHC.

  6. Ability to understand and the willingness to sign a written informed consent/assent document
  7. Have a tumor genomic profile for which treatment with one of the approved targeted anti-cancer therapies included in this study has potential clinical benefit based on the criteria described in Section 7.0.
  8. For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
  9. Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) in combination with inhibition of ovulation (intrauterine device (IUD), intrauterine hormone-releasing system ( IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence) for the duration of study participation, and for four to 24 months following completion of study therapy (depending on SPC from individual drugs). Should a woman become pregnant or suspect she is pregnant while participating in this study or if she is the partner of a male participant in this study and becomes pregnant while he is participating in this study, she should inform her or her partner's treating physician immediately as well as her obstetrician. Female study patients who become pregnant must immediately discontinue treatment with any study therapy. Male patients should avoid impregnating a female partner. Male study 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 > CTCAE grade 2, other than peripheral neuropathy, related to anti-tumor treatment that was completed within 4 weeks prior to registration. Patients with ongoing peripheral neuropathy of ≥ CTCAE grade 3 will be excluded.
  2. Previous treatment with the selected study drug for the same malignancy.
  3. If the patient's tumor has a genomic variant known to confer resistance to an anti-cancer agent available in this study, the patient will not be eligible to receive that agent but will be eligible to receive other drugs available in this study if all inclusion and exclusion criteria are met for that drug.
  4. 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) or ongoing castration-intent therapy for prostate cancer. These medications must have been started ≥ 1 month prior to enrollment on this study. Patients may be on warfarin, low molecular weight heparin or direct factor Xa inhibitors, unless such therapies are prohibited by drug-specific exclusion criteria.
  5. Female patients who are pregnant or nursing. Male and female patients who refuse to practice highly effective contraception methods.
  6. Patients with known progressive brain metastases determined by serial imaging or declining neurologic function in the opinion of the treating physician are not eligible. 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 clinically stable for at least 1 month after completion of treatment and off steroid treatment for one month prior to study enrollment.

    Additional exclusion criteria specific for GBM 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.
  7. Patients with preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure are not eligible.
  8. Patients with left ventricular ejection fraction (LVEF) known to be < 40% are not eligible.
  9. Patients with stroke (including TIA) or acute myocardial infarction within 4 months before the first dose of study treatment are not eligible
  10. Patients with acute gastrointestinal bleeding within 1 month of start of treatment are not eligible.
  11. 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, severe psychiatric illness situations, or anticipated or planned anti-cancer treatment or surgery.
  12. Patients who do not meet drug-specific eligibility requirements for the drug selected by the investigator, are not eligible to receive that drug.
  13. Patients whose disease is not measurable or assessable by radiographic imaging or physical examination (e.g., elevated serum tumor marker only) are not eligible.
  14. Patients with known allergy/hypersensitivity to the study drug (active substance or to any of the excipients).

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): NCT04341181


Contacts
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Contact: Ulrik Lassen, Prof. +45 3545 8923 ulrik.lassen@regionh.dk
Contact: Kristoffer S Rohrberg, MD, PhD +45 3545 6353 kristoffer.staal.rohrberg@regionh.dk

Locations
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Denmark
Aalborg University Hospital Not yet recruiting
Aalborg, Denmark, 9000
Contact: Morten Ladekarl, MD, Prof.         
Aarhus University Hospital Not yet recruiting
Aarhus, Denmark, 8200
Contact: Britt E Laursen, MD, PhD         
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Kristoffer S Rohrberg, MD, PhD         
Herlev Hospital Not yet recruiting
Herlev, Denmark, 2730
Contact: Rikke L Eefsen, MD, PhD         
Odense University Hospital Not yet recruiting
Odense, Denmark, 5000
Contact: Karin Holmskov, MD         
Zealand University Hospital Not yet recruiting
Roskilde, Denmark, 4000
Contact: Julie Gehl, MD         
Vejle Sygehus Not yet recruiting
Vejle, Denmark, 7100
Contact: Lars H Jensen, MD, PhD         
Sponsors and Collaborators
Ulrik Lassen
Roche Pharma AG
Pfizer
GlaxoSmithKline
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Responsible Party: Ulrik Lassen, Professor, MD, PhD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT04341181    
Other Study ID Numbers: ProTarget
First Posted: April 10, 2020    Key Record Dates
Last Update Posted: September 25, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Neoplasms
Trastuzumab
Avelumab
Pertuzumab
Ado-Trastuzumab Emtansine
Atezolizumab
Axitinib
Niraparib
Vemurafenib
Maytansine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators