GlioblastomaPhase 2NCT01520870
Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT.
A Phase 2 study testing PF-299804 (Dacomitinib) in people with Glioblastoma and Brain Tumor, Recurrent, run by Grupo Español de Investigación en Neurooncología at 12 sites in Spain.
Trial summary
This multicenter, 2-stage, open-label, phase II trial aims to assess the efficacy and safety of dacomitinib in adult patients with recurrent Glioblastoma (GBM) with EGFR gene amplification and/or EGFRvIII mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Brain Tumor, Recurrent
- What is being tested?
- PF-299804 (Dacomitinib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 12 sitesSpain
- Study dates
- Feb 2012to 9 Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and sign the informed consent approved by the Ethic Committee.
- Men or women aged greater than or equal to 18.
- Patients with grade IV malignant glioma according to WHO classification (glioblastoma) in first relapse with histologically confirmed diagnosis by the central laboratory. Patients with previous low-grade glioma or anaplastic glioma (anaplastic astrocytoma or anaplastic oligodendroglioma), are not eligible, even if histological assessment demonstrates transformation to GBM.
- Patients in first relapse (or progression) to chemo-radiotherapy and temozolomide-based chemotherapy (Stupp4 scheme).
- All patients must have EGFR gene amplification by in situ hybridization fluorescent (FISH) and / or EGFRvIII mutation by PCR in tumor samples made by the central laboratory (Laboratory of Neuropathology. Hospital Universitario 12 de Octubre).
- For all study cohorts, patients must be at least 15 unstained slides or a block of paraffin-embedded tissue available from a previous biopsy or surgery (archived tumor samples previously).
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- All patients must show progressive disease of the brain MRI is as defined in the Criteria RANO.
- Interval of at least one week between prior intra-cranial biopsy, healed properly, and inclusion.
- Interval of at least 12 weeks between prior radiotherapy and inclusion, unless: a) histopathologic confirmation of recurrent tumor, or b) MR recurrence outside the radiation field.
- Patients must have recovered from previous therapy: 28 days from the completionof any investigational drug and / or the termination of any cytotoxic therapy.
- ECOG performance status less than or equal to 2.
- Stable or decreasing doses of corticosteroids during the five days prior to inclusion in the study.
- Adequate bone marrow reserve, hematocrit greater than or equal to 29%, WBC> 3000 / mcl,ANC greater than or equal to 1,500 cells / ul, platelets greater than or equal a100.000 cells / ul.
- Adequate hepatic function: bilirubin less than or equal to 1.5 times ULN, AST (SGOT) less than or equal to 2.5 x ULN.
- Creatinine within the center ULN or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels above the center ULN.
- The patients in whom resection was made in the first tumor recurrence are eligible in the following cases:
- There is adequate recovery from surgery.
- There must be measurable or evaluable disease after surgery. For an adequate Radiological evaluation of residual disease, MRI must be completed within 72 hours after surgery or 4 weeks after surgery.
- The effects of PF-00299804 in human foetal development are unknown. For this reason, women of childbearing potential and men must agree to use effective contraception (hormonal control method, barrier, abstinence or surgical sterilization) before inclusion in the study, during participating in the study and at least 3 months after treatment has ended the trial. The definition of an effective contraceptive method is based on the criterion of the principal investigator or designee. In case of a woman become pregnant or there is suspicion that she is pregnant while participating in this study, the trial physician must inform immediately. All women of childbearing potential must have a negative pregnancy test (serum / urine) in the 2 weeks before the start of treatment. NOTE: Patients who have received treatment based on the scheme Stupp (Chemoradiotherapy with temozolomide followed by temozolomide sequential) are eligible in the trial, even if other drugs have been added to this scheme. It is excluded from this, those patients who have been treated with EGFR inhibitors for obvious reasons. However, those patients who have received Stupp scheme + other drugs like bevacizumab and cilengitide, remain eligible.
Who cannot join
- Presence of extra-cranial metastatic disease.
- Concomitant treatment with other investigational drugs.
- Prior treatment with an investigational drug/s known or are suspected to be active by the action of any component of the EGFR tyrosine kinase.
- Surgery of any kind (does not include diagnostic procedures such as minor lymph node biopsy) in the 2 weeks prior to baseline assessments of the disease, or presence of side effects of previous procedures.
- Presence of any clinically significant gastrointestinal abnormality that can affect oral administration, transit or absorption of study drug, such as the inability to take medication by mouth as tablets.
- Presence of any psychiatric or cognitive disorder that limits the understanding or the signature of informed consent and / or jeopardize the fulfillment of the requirements of this protocol.
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- Significant or uncontrolled cardiovascular disease, including:
- Myocardial infarction within the previous 12 months
- Uncontrolled angina within the previos 6 months
- Congestive heart failure in the previous 6 months
- Known or suspected congenital long QT syndrome
- History of clinically significant ventricular arrhythmias of any type (as ventricular tachycardia, ventricular fibrillation or torsades de pointes)
- QTc prolongation on electrocardiogram prior to entry (> 470 msec)
- History of second or third grade heart block (these patients may be eligible if you currently have a pacemaker)
- Heart rate < 50/minute in the baseline electrocardiogram
- Uncontrolled hypertension.
- Any patient with a history of significant cardiovascular disease, even though is currently controlled, or presents signs or symptoms suggestive of impaired left ventricular function at discretion of the investigator,should have an evaluation of LVEF in these circumstances. If the result is under the center lower limit normal or lower than 50%, the patient would not be eligible.
- History of any cancer, except for the following circumstances:
- Patients with a history of other malignancies are eligible if they have been free of disease for at least the last 3 years, and at the discretion of the investigator, there is low risk of disease recurrence.
- Patients with the following cancers are eligible even if they are diagnosed and treated in the last 3 years: carcinoma in situ of the cervix and basal cell or basal cell skin carcinoma. Patients are ineligible if there is evidence of any neoplastic disease that required therapy other than surgery in the past 3 years.
- Prior stereotactic radiotherapy or brachytherapy.
- Intratumoral treatment with CCNU in recurrent tumor surgery (second surgery). NOTE: Patients treated with intratumoral CCNU (or what is the same (intratumor carmustine or Gliadel®), in the first intervention can participate in the study.
- Presence of leptomeningeal dissemination.
- Pregnant or breastfeeding. Pregnant women are excluded from this study because the potential for teratogenic or abortifacient effects of PF-00299804 is unknown. Because there is an unknown risk of potential adverse effects in infants, secondary to maternal treatment with PF-00299804, breastfeeding should be discontinued if mother is treated with PF-00299804.
- Patients positive for HIV being treated with antiretroviral combination therapy. These patients are not eligible due to potential pharmacokinetic interactions with PF-00299804. Additionally, these subjects have an increased risk of lethal infections when treated with marrow-suppressive therapy. HIV-positive patients not on antiretroviral combination therapy, are eligible if the disease is controlled at the discretion of the investigator.
- History of allergic reactions attributed to drugs with similar chemical or biological composition than PF-00299804.
- Another acute or chronic serious medical condition, uncontrolled intercurrent illness or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of test results and that,investigator's discretion, make the patient inappropriate for entry into this trial. Uncontrolled intercurrent illness including, but are not limited to, ongoing or active infection or psychiatric illness / social situations that limit the compliance of study requirements.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Spain12 sites
Hospital Universitario A Coruña
A Coruña, Coruña (A), 15006
Hospital Universitari Germans Trias I Pujol de Badalona
Badalona, Barcelona, 08916
Hospital Del Mar
Barcelona, 08003
Hospital de La Santa Creu I Sant Pau
Barcelona, 08025
Complejo Hospitalario Regional Virgen de Las Nieves
Granada, 18004
Institut Català D'Oncologia L'Hospitalet (Ico)
L'Hospitalet de Llobregat, Barcelona, 08908
Complejo Hospitalario Universitario Insular-Materno Infantil
Las Palmas de Gran Canaria, 35016
Hospital Ramón Y Cajal
Madrid, 28034
Hospital Clínico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Regional Universitario de Malaga
Málaga
Hospital Universitario Y Politécnico La Fe
Valencia, 46009
About this study
Official title: Phase II Pilot, Prospective, Open Label, Multicenter CT, to Evaluate the Safety and Efficacy of PF299804, a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation
This multicenter, 2-stage, open-label, phase II trial aims to assess the efficacy and safety of dacomitinib in adult patients with recurrent Glioblastoma (GBM) with EGFR gene amplification and/or EGFRvIII mutation.
- Conditions
- Glioblastoma, Brain Tumor, Recurrent
- Being tested
- PF-299804 (Dacomitinib)
- Keywords
- Dacomitinib, PF-299804, Glioblastoma, Recurrent, EGFR
- Medical subject headings
- Glioblastoma, Brain Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-299804 (Dacomitinib)Drug
Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
| Study group | Role | What they receive |
|---|---|---|
| PF-299804 (Dacomitinib) | Experimental | Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. Receives: Drug: PF-299804 (Dacomitinib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) at Six Months (PFS6m)
Percentage of patients who have progressed / no progress after 6 months of treatment in each of the two cohorts.
Measured: Baseline and after 6 months
Secondary outcomes (6)
Safety and Tolerability of Oral Administration of PF-00299804.
Type, incidence, severity, frequency, severity and relationship with IMP of reported adverse events, physical examinations and laboratory tests. Toxicity will be classified and tabulated by NCI-CTCAE v 4.0.
Measured: Up to 42 months
Anti-tumor Response
According to RANO criteria. Based on neurological symptoms, doses of dexamethasone and radiological response, assessed by the PI of each center. There will be central review of MRI.
Measured: Baseline and every 12 weeks
Overall Survival (OS)
Time from randomization to death by any cause.
Measured: Up to 42 months
Response Duration
Time from first objective response up to disease progression according RANO (in patients with objective responses).
Measured: Baseline and every 12 weeks
Changes in the Use of Glucocorticoids
Percentage of patients decreasing doses of corticosteroids during treatment.
Measured: Baseline and every 12 weeks
Changes in Neurological Status.
By means of minimental test, it will be determined the changes in neurological status of patients.
Measured: Baseline and every 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2012 (estimated)
- Study startFeb 2012
- Primary completionApr 2015
- Study completion9 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Español de Investigación en Neurooncología
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Juan Sepúlveda, MD, Principal investigator, Hospital 12 de Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01520870
- Sponsor's protocol ID
- GEINO 11
- Status last verified
- Jul 2021
- First submitted
- 18 Jan 2012
- Last updated
- 6 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Pilot, Prospective, Open Label, Multicenter CT, to Evaluate the Safety and Efficacy of PF299804, a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation
- ClinicalTrials.gov ID
- NCT01520870
- Acronym / sponsor ID
- GEINO 11
- Conditions
- Glioblastoma, Brain Tumor, Recurrent
- Keywords
- Dacomitinib, PF-299804, Glioblastoma, Recurrent, EGFR
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Grupo Español de Investigación en NeurooncologíaUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Feb 2012
- Primary completion
- Apr 2015 (actual)
- Study completion
- 9 Mar 2017 (actual)
- First posted
- 30 Jan 2012 (estimated)
- Results
- Posted 6 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multicenter, 2-stage, open-label, phase II trial aims to assess the efficacy and safety of dacomitinib in adult patients with recurrent Glioblastoma (GBM) with EGFR gene amplification and/or EGFRvIII mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PF-299804 (Dacomitinib) | Experimental | Drug: PF-299804 (Dacomitinib)Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Ability to understand and sign the informed consent approved by the Ethic Committee.
- Men or women aged greater than or equal to 18.
- Patients with grade IV malignant glioma according to WHO classification (glioblastoma) in first relapse with histologically confirmed diagnosis by the central laboratory. Patients with previous low-grade glioma or anaplastic glioma (anaplastic astrocytoma or anaplastic oligodendroglioma), are not eligible, even if histological assessment demonstrates transformation to GBM.
- Patients in first relapse (or progression) to chemo-radiotherapy and temozolomide-based chemotherapy (Stupp4 scheme).
- All patients must have EGFR gene amplification by in situ hybridization fluorescent (FISH) and / or EGFRvIII mutation by PCR in tumor samples made by the central laboratory (Laboratory of Neuropathology. Hospital Universitario 12 de Octubre).
Key exclusion criteria (27 listed)
- Presence of extra-cranial metastatic disease.
- Concomitant treatment with other investigational drugs.
- Prior treatment with an investigational drug/s known or are suspected to be active by the action of any component of the EGFR tyrosine kinase.
- Surgery of any kind (does not include diagnostic procedures such as minor lymph node biopsy) in the 2 weeks prior to baseline assessments of the disease, or presence of side effects of previous procedures.
- Presence of any clinically significant gastrointestinal abnormality that can affect oral administration, transit or absorption of study drug, such as the inability to take medication by mouth as tablets.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-299804 (Dacomitinib)Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. | Drug | PF-299804 (Dacomitinib) |
Primary outcome
Progression-free Survival (PFS) at Six Months (PFS6m)
Time frame: Baseline and after 6 months
Percentage of patients who have progressed / no progress after 6 months of treatment in each of the two cohorts.
6 secondary outcomes
Safety and Tolerability of Oral Administration of PF-00299804.
Time frame: Up to 42 months
Anti-tumor Response
Time frame: Baseline and every 12 weeks
Overall Survival (OS)
Time frame: Up to 42 months
Response Duration
Time frame: Baseline and every 12 weeks
Changes in the Use of Glucocorticoids
Time frame: Baseline and every 12 weeks
Changes in Neurological Status.
Time frame: Baseline and every 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Sepúlveda, MD principal investigator
Hospital 12 de Octubre
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-299804 (Dacomitinib) in people with Glioblastoma and Brain Tumor, Recurrent, run by Grupo Español de Investigación en Neurooncología at 12 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) at Six Months (PFS6m) (time frame: Baseline and after 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2021.