GlioblastomaPhase 2NCT01112527
PF-00299804 in Adult Patients With Relapsed/Recurrent Glioblastoma
A Phase 2 study testing PF-00299804 in people with Glioblastoma and GBM, run by Massachusetts General Hospital at 4 sites in United States.
Trial summary
There are three arms to this study (A, B and C) The purpose of this research study during Arm A is to see how much of PF-00299804 gets into the brain tumor. For many brain tumors, one reason that chemotherapy drugs might not be effective is that the drug may not be able to get into the brain tumor and kill the cancer… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, GBM, Glioblastoma Multiforme
- What is being tested?
- PF-00299804
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 4 sitesUnited States
- Study dates
- Apr 2010to Sep 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- 18 years of age or older
- Histologically confirmed diagnosis of a recurrent primary WHO grade IV malignant glioma (glioblastoma). Patients with recurrent disease whose diagnostic pathology confirmed glioblastoma will not need re-biopsy. Patients with prior low-grade glioma or anaplastic glioma are eligible if histologic assessment demonstrates transformation to GBM.
- Evidence of EGFR gene amplification by fluorescence in situ hybridization (FISH) in archival tumor material.
- Patients must have at least 15 unstained slides or 1 tissue block (frozen or paraffin embedded) available from a prior biopsy or surgery.
- For Arm A: patients must be at first recurrence of GBM, must not have had previous anti-VEGF therapy, and must be candidates for surgical partial or gross-total resection.
- For Arm B: patients must be at first recurrence of GBM and must not have had prior anti-VEGF therapy.
Show all 15Show fewer
- For Arm C: patients may have had an unlimited number of prior therapies for GBM, however must be at first recurrence from a therapeutic regimen containing bevacizumab
- Progressive disease on contrast-enhanced brain CT or MRI as defined by McDonald Criteria, or have documented recurrent glioblastoma on diagnostic biopsy.
- Prior to enrollment, there must be an interval of at least 2 weeks between prior surgical resection (1 week for intracranial biopsy) and adequate wound healing.
- Interval of at least 12 weeks from prior radiotherapy unless there is either: a) histopathologic confirmation of recurrent tumor, or b) new enhancement on MRI outside of XRT treatment field.
- Patients must have sufficient time to recover from prior therapy.
- Karnofsky Performance Score 70% or greater
- Adequate hematologic and liver function as outlined in the protocol
- Creatinine within normal institutional limits
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation and for at least 3 months thereafter.
Who cannot join
- Presence of extra-cranial metastatic disease
- Participants may not be receiving any other investigational agents
- Prior investigational therapy with an agent that is known or proposed to be active by action on any component of the EGFR tyrosine kinase, IGF1R, mTor, orc-MET pathways
- Patients who have been previously treated with an anti-VEGF agent will be excluded from Arm A and Arm B.
- Patients must not have received prior Gliadel wafers
- For participants in Arm A, if the diagnostic pathology of the biopsy specimen is not consistent with recurrent glioblastoma, then the participant must be taken off study and be replaced with another participant that meets the inclusion criteria and is eligible for surgical resection.
Show all 19Show fewer
- Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
- Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug.
- Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol
- Patients with known interstitial lung disease
- Uncontrolled or significant cardiovascular disease
- Any patient with a history of significant cardiovascular disease, even if currently controlled, or who has signs or symptoms suggesting impaired left ventricular function in the judgment of the investigator must have a screening left ventricular ejection fraction evaluation by ECHO or MUGA. Patients with LVEF measurements below local institutional lower limit of normal or less then 50% will not be eligible.
- Individuals with a history of a different malignancy are ineligible except for the circumstances outlined in the protocol
- Patients who have had prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy as gliosis/scarring from these modalities may limit delivery
- Patients will not be eligible if they present with leptomeningeal dissemination
- Pregnant women
- HIV-positive individuals on combination antiretroviral therapy are ineligible
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PF-00299804
- Other severe acute or chronic medical condition, uncontrolled intercurrent illness or laboratory abnormality that may increase the risk associated with trial participation or investigation product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Cleveland Clinic
Cleveland, Ohio, 44195
Henry Ford Hospital
Detroit, Michigan, 48202
About this study
Official title: An Open-Label, Phase 2 Trial of Orally Administered PF-00299804 in Adult Patients With Relapsed/Recurrent Glioblastoma (GBM)
There are three arms to this study (A, B and C) The purpose of this research study during Arm A is to see how much of PF-00299804 gets into the brain tumor. For many brain tumors, one reason that chemotherapy drugs might not be effective is that the drug may not be able to get into the brain tumor and kill the cancer cells. We will determine how much PF-00299804 gets into the brain tumor by obtaining a sample of the tumor from the surgery that the participant already has scheduled. The purpose of this research study during Arm B and C, is to determine how well PF-00299804 works in killing cancer cells. PF-00299804 works by binding to specific proteins found on the surface of some cancer cells that promote a growth signal. Blocking this signal from reaching its target on the cancer cells may slow or stop the cancer from growing.
Read the detailed description
ARM A:
- Each treatment cycle lasts four weeks (28 days). There are no breaks from taking PF-00299804 between treatment cycles. Participants will take PF-00299804 once a day for a total of 7 to 9 days before surgery. They will then stop taking PF-00299804 until they have recovered from surgery.
- Once they have recovered from surgery, they will continue to take PF-00299804 once a day until their disease worsens, they experience side effects or they decide to stop study treatment.
- The following tests and procedures will be performed at the time intervals specified: Research blood tests (Day 1 of study drug administration, day of surgery, day 1 of all cycles after surgery, day 14 of the first cycle after surgery); tissue samples (day of surgery); physical and neuro exams (day 1 of all cycles after surgery); skin exam (day 1 of all cycles after surgery and day 14 of the first cycle after surgery).
- An assessment of the tumor by CT or MRI scan will be made within 24 hours after surgery. Another assessment by CT or MRI scan will be made at the end of cycle 2 and then at the end of every even numbered cycle thereafter.
ARM B \& C:
- Each treatment cycle lasts four weeks (28 days). There are no breaks from taking PF-00299804 between treatment cycles. Participants will take PF-00299804 orally once a day until their disease worsens, they experience any side effect, or if they decide to stop study treatment.
- Participants will come into the clinic on Day 1 and Day 14 of Cycle 1, and then on Day 1 of all subsequent cycles for some of the following tests and procedures: research blood tests, physical and neuro exams, skin exam, urine test and Patient Reported Outcomes questionnaire.
- An assessment of the participants tumor by CT scan or MRI scans will be done at the end of Cycle 2, 4 and then every other cycle thereafter.
- Conditions
- Glioblastoma, GBM, Glioblastoma Multiforme
- Being tested
- PF-00299804
- Keywords
- PF-00299804
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-00299804Drug
Taken orally once a day
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Patients with Glioblastoma that has returned or grown after chemotherapy or radiation treatment and who will be having a standard operation to remove the tumor. Receives: Drug: PF-00299804 |
| Arm B | Experimental | Participants with glioblastoma at first recurrence who are not surgical candidates and who have not had prior anti-VEGF therapy. Receives: Drug: PF-00299804 |
| Arm C | Experimental | Participants with glioblastoma who are not surgical candidates and who are at first recurrence from a therapeutic regimen containing bevacizumab. Receives: Drug: PF-00299804 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival
Assess progression-free survival at six months in patients with recurrent GBM and EGFR amplification in archival tumor material who are treated with continuous daily dosing of PF-00299804 (Arm B)
Measured: 2 years
Secondary outcomes (3)
Ability of PF-00299804 to cross the blood-brain barrier
Assess the ability of PF-00299804 to cross the blood-brain barrier in GBM patients who are candidates for surgical re-section in Arm A.
Measured: 2 years
Safety and tolerability
Evaluate the safety and tolerability of orally administered PF-00299804 on a continuous dosing schedule in patients with recurrent GBM.
Measured: 2 years
Anti-tumor response
Assess anti-tumor response in patients in Arm B
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Henry Ford Hospital, Pfizer
- Responsible party
- Principal investigator, Tracy T. Batchelor, MD, Massachusetts General Hospital
- Investigators
- Tracy T. Batchelor, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01112527
- Sponsor's protocol ID
- 09-468
- Other IDs
- WS573383
- Status last verified
- Aug 2018
- First submitted
- 27 Apr 2010
- Last updated
- 16 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 2 Trial of Orally Administered PF-00299804 in Adult Patients With Relapsed/Recurrent Glioblastoma (GBM)
- ClinicalTrials.gov ID
- NCT01112527
- Acronym / sponsor ID
- 09-468
- Conditions
- Glioblastoma, GBM, Glioblastoma Multiforme
- Keywords
- PF-00299804
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Henry Ford Hospital, Pfizer
- Study start
- Apr 2010
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 28 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There are three arms to this study (A, B and C) The purpose of this research study during Arm A is to see how much of PF-00299804 gets into the brain tumor. For many brain tumors, one reason that chemotherapy drugs might not be effective is that the drug may not be able to get into the brain tumor and kill the cancer cells. We will determine how much PF-00299804 gets into the brain tumor by obtaining a sample of the tumor from the surgery that the participant already has scheduled. The purpose of this research study during Arm B and C, is to determine how well PF-00299804 works in killing cancer cells. PF-00299804 works by binding to specific proteins found on the surface of some cancer cells that promote a growth signal. Blocking this signal from reaching its target on the cancer cells may slow or stop the cancer from growing.
Detailed description
ARM A:
- Each treatment cycle lasts four weeks (28 days). There are no breaks from taking PF-00299804 between treatment cycles. Participants will take PF-00299804 once a day for a total of 7 to 9 days before surgery. They will then stop taking PF-00299804 until they have recovered from surgery.
- Once they have recovered from surgery, they will continue to take PF-00299804 once a day until their disease worsens, they experience side effects or they decide to stop study treatment.
- The following tests and procedures will be performed at the time intervals specified: Research blood tests (Day 1 of study drug administration, day of surgery, day 1 of all cycles after surgery, day 14 of the first cycle after surgery); tissue samples (day of surgery); physical and neuro exams (day 1 of all cycles after surgery); skin exam (day 1 of all cycles after surgery and day 14 of the first cycle after surgery).
- An assessment of the tumor by CT or MRI scan will be made within 24 hours after surgery. Another assessment by CT or MRI scan will be made at the end of cycle 2 and then at the end of every even numbered cycle thereafter.
ARM B \& C:
- Each treatment cycle lasts four weeks (28 days). There are no breaks from taking PF-00299804 between treatment cycles. Participants will take PF-00299804 orally once a day until their disease worsens, they experience any side effect, or if they decide to stop study treatment.
- Participants will come into the clinic on Day 1 and Day 14 of Cycle 1, and then on Day 1 of all subsequent cycles for some of the following tests and procedures: research blood tests, physical and neuro exams, skin exam, urine test and Patient Reported Outcomes questionnaire.
- An assessment of the participants tumor by CT scan or MRI scans will be done at the end of Cycle 2, 4 and then every other cycle thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: PF-00299804Patients with Glioblastoma that has returned or grown after chemotherapy or radiation treatment and who will be having a standard operation to remove the tumor. |
| Arm B | Experimental | Drug: PF-00299804Participants with glioblastoma at first recurrence who are not surgical candidates and who have not had prior anti-VEGF therapy. |
| Arm C | Experimental | Drug: PF-00299804Participants with glioblastoma who are not surgical candidates and who are at first recurrence from a therapeutic regimen containing bevacizumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 18 years of age or older
- Histologically confirmed diagnosis of a recurrent primary WHO grade IV malignant glioma (glioblastoma). Patients with recurrent disease whose diagnostic pathology confirmed glioblastoma will not need re-biopsy. Patients with prior low-grade glioma or anaplastic glioma are eligible if histologic assessment demonstrates transformation to GBM.
- Evidence of EGFR gene amplification by fluorescence in situ hybridization (FISH) in archival tumor material.
- Patients must have at least 15 unstained slides or 1 tissue block (frozen or paraffin embedded) available from a prior biopsy or surgery.
- For Arm A: patients must be at first recurrence of GBM, must not have had previous anti-VEGF therapy, and must be candidates for surgical partial or gross-total resection.
Key exclusion criteria (19 listed)
- Presence of extra-cranial metastatic disease
- Participants may not be receiving any other investigational agents
- Prior investigational therapy with an agent that is known or proposed to be active by action on any component of the EGFR tyrosine kinase, IGF1R, mTor, orc-MET pathways
- Patients who have been previously treated with an anti-VEGF agent will be excluded from Arm A and Arm B.
- Patients must not have received prior Gliadel wafers
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-00299804Taken orally once a day | Drug | Arm A, Arm B, Arm C |
Primary outcome
Progression-Free Survival
Time frame: 2 years
Assess progression-free survival at six months in patients with recurrent GBM and EGFR amplification in archival tumor material who are treated with continuous daily dosing of PF-00299804 (Arm B)
3 secondary outcomes
Ability of PF-00299804 to cross the blood-brain barrier
Time frame: 2 years
Safety and tolerability
Time frame: 2 years
Anti-tumor response
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2018.
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
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.
Tracy T. Batchelor, MD principal investigator
Massachusetts General Hospital
4 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-00299804 in people with Glioblastoma and GBM, run by Massachusetts General Hospital at 4 sites in United States.
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 15 inclusion and 19 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 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 (time frame: 2 years). 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 16 Aug 2018.