Newly Diagnosed Glioblastoma MultiformePhase 2NCT01591577
Lapatinib With Temozolomide and Regional Radiation Therapy for Patients With Newly-Diagnosed Glioblastoma Multiforme
A Phase 2 study testing Lapatinib/Temozolomide/radiation in people with Newly Diagnosed Glioblastoma Multiforme, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and effects of a combination of a study drug, Lapatinib, plus the administration of standard radiation therapy and an FDA approved drug Temozolomide (chemotherapy agent) in patients with newly diagnozed glioblastoma Multiforme.Currently, only radiation therapy and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Newly Diagnosed Glioblastoma Multiforme
- What is being tested?
- Lapatinib/Temozolomide/radiation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2012to 7 May 2024
- 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
- Patients will be included in the study based on the following criteria:
- Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM) or gliosarcoma (GS). This includes treatment-naïve patients with prior tissue diagnoses of lower grade gliomas that have been upgraded to GBM after repeat resection.
- Patients must have available archived tissues of 20-30 unstained slides. If frozen tissues are available, at least 200mg would be preferred, but not mandatory for study eligibility.
- Use of effective means of contraception (men and women) in subjects of child-bearing potential
- Cranial MRI or contrast CT must have been performed within 21 days of study entry. The use of MRI rather than CT is preferred. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. If the surgical procedure was a resection, cranial MRI or contrast CT performed within 96 hours of resection is preferred but not required. If the surgical procedure was a biopsy only, a head CT within 96 hours of the biopsy is acceptable. Patients without measurable or assessable disease are eligible.
- Patients must begin partial brain radiotherapy and temozolomide chemotherapy no sooner than 2 weeks and no later than 5 weeks from the surgery in which tissue was collected. Patients with GBM diagnosis from surgeries in which tissue was not collected will be eligible after repeat surgery performed to collect tissue, as long as no treatment has been initiated prior to surgery in which tissue was collected. In this case, initiation of treatment must begin within 2 to 5 weeks from the last surgery. Patients may have radiotherapy administered at outside facilities according to the specified guidelines (Appendix F). Radiotherapy must be given within 2 days of lapatinib initiation and by external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned total dose to the tumor of 60.0 Gy in accordance with Appendix F. Stereotactic radiosurgery and brachytherapy will not be allowed.
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- Patients must be willing to forego other drug therapy against the tumor while being treated with pulse dosing of lapatinib and temozolomide and radiation and subsequently pulse dosing lapatinib and temozolomide.
- All patients must sign an informed consent approved by the Institutional Review Board indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information.
- Patients must be > 18 years old, and with a life expectancy > 12 weeks.
- Patients must have a Karnofsky performance status of > 60.
- Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl) and the test must be performed within 14 days prior to treatment initiation. Eligibility level for hemoglobin may be reached by transfusion.
- Patients must have adequate liver function (AST, ALT < 2.5 times ULN, and bilirubin < 1.5 times ULN) and the test must be performed within 14 days prior to treatment initiation.
- Patients must have adequate renal function (creatinine < 1.5 mg/dL) before starting therapy and the test must be performed within 14 days prior to treatment initiation.
Who cannot join
- Patients who received previous radiotherapy to the brain.
- Patients who received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor. Patients who received Gliadel wafers will be excluded. Patients may have received or be receiving corticosteroids, analgesics, and other drugs to treat symptoms or prevent complications.
- Patients who may be receiving any EIAED (see Appendix C) within 2 weeks prior to registration, or any other prohibited medications within the Washout Period per Appendix D prior to registration. See section 6.5 for seizure medication managements.
- Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
- Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
- Women who are pregnant (determined by high titer of serum beta-HCG) or Breast-feeding. (Women with reproductive potential must practice adequate contraception.)
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- Patients who have any disease that will obscure toxicity or dangerously alter drug metabolism.
- Patients who have serious uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring IV antibiotics and psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state (HIV, SLE, etc.).
- Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Pulse Dosing of Lapatinib in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-Diagnosed Glioblastoma Multiforme
The purpose of this study is to test the safety and effects of a combination of a study drug, Lapatinib, plus the administration of standard radiation therapy and an FDA approved drug Temozolomide (chemotherapy agent) in patients with newly diagnozed glioblastoma Multiforme.Currently, only radiation therapy and Temozolomide chemotherapy are standard treatment for brain cancer.Lapatinib has not been FDA approved for use in brain tumors treatment. It has been approved to be used as a daily treatment with other chemotherapies by the FDA for the treatment of advanced breast cancer.
The purpose of this study is to find the answers to the following research questions:
- Is Lapatinib given twice a week at higher dosages, with radiation therapy and Temozolomide, safe when given to patients with brain tumor?
- What are the side effects of Lapatinib given twice a week at higher dosages when given with radiation therapy and Temozolomide and how often do they occur?
- Can Lapatinib, radiation, and Temozolomide be effective in shrinking tumors when given to patients with brain tumors?
- To determine whether the presence of genetic alterations specific proteins in the tumor samples can predict whether this study drug is effective on the tumor.
- Conditions
- Newly Diagnosed Glioblastoma Multiforme
- Being tested
- Lapatinib/Temozolomide/radiation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapatinib/Temozolomide/radiationOther
Patients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression.
| Study group | Role | What they receive |
|---|---|---|
| Lapatinib/Temozolomide/radiation | Experimental | Patients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression. Receives: Other: Lapatinib/Temozolomide/radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
The primary objective is to estimate the overall survival in subjects with newly-diagnosed glioblastoma treated with lapatinib/temozolomide/radiation followed by lapatinib/temozolomide for 2 years or until progression is detected. If no progression is seen at 2 years, then single-agent lapatinib will be continued until progression.
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 posted4 May 2012 (estimated)
- Study start7 Dec 2012
- Primary completion7 May 2024
- Study completion7 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Newly Diagnosed Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Novartis
- Responsible party
- Sponsor
- Investigators
- Pioanh Nghiemphu, M D, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01591577
- Sponsor's protocol ID
- 12-000493
- Status last verified
- May 2024
- First submitted
- 2 May 2012
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yu A, Faiq N, Green S, Lai A, Green R, Hu J, Cloughesy TF, Mellinghoff I, Nghiemphu PL. Report of safety of pulse dosing of lapatinib with temozolomide and radiation therapy for newly-diagnosed glioblastoma in a pilot phase II study. J Neurooncol. 2017 Sep;134(2):357-362. doi: 10.1007/s11060-017-2533-6. Epub 2017 Jul 1.
PubMed 28669012
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Pulse Dosing of Lapatinib in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-Diagnosed Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT01591577
- Acronym / sponsor ID
- 12-000493
- Conditions
- Newly Diagnosed Glioblastoma Multiforme
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, Novartis
- Study start
- 7 Dec 2012 (actual)
- Primary completion
- 7 May 2024 (actual)
- Study completion
- 7 May 2024 (actual)
- First posted
- 4 May 2012 (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.
The purpose of this study is to test the safety and effects of a combination of a study drug, Lapatinib, plus the administration of standard radiation therapy and an FDA approved drug Temozolomide (chemotherapy agent) in patients with newly diagnozed glioblastoma Multiforme.Currently, only radiation therapy and Temozolomide chemotherapy are standard treatment for brain cancer.Lapatinib has not been FDA approved for use in brain tumors treatment. It has been approved to be used as a daily treatment with other chemotherapies by the FDA for the treatment of advanced breast cancer.
The purpose of this study is to find the answers to the following research questions:
- Is Lapatinib given twice a week at higher dosages, with radiation therapy and Temozolomide, safe when given to patients with brain tumor?
- What are the side effects of Lapatinib given twice a week at higher dosages when given with radiation therapy and Temozolomide and how often do they occur?
- Can Lapatinib, radiation, and Temozolomide be effective in shrinking tumors when given to patients with brain tumors?
- To determine whether the presence of genetic alterations specific proteins in the tumor samples can predict whether this study drug is effective on the tumor.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lapatinib/Temozolomide/radiation | Experimental | Other: Lapatinib/Temozolomide/radiationPatients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients will be included in the study based on the following criteria:
- Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM) or gliosarcoma (GS). This includes treatment-naïve patients with prior tissue diagnoses of lower grade gliomas that have been upgraded to GBM after repeat resection.
- Patients must have available archived tissues of 20-30 unstained slides. If frozen tissues are available, at least 200mg would be preferred, but not mandatory for study eligibility.
- Use of effective means of contraception (men and women) in subjects of child-bearing potential
- Cranial MRI or contrast CT must have been performed within 21 days of study entry. The use of MRI rather than CT is preferred. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. If the surgical procedure was a resection, cranial MRI or contrast CT performed within 96 hours of resection is preferred but not required. If the surgical procedure was a biopsy only, a head CT within 96 hours of the biopsy is acceptable. Patients without measurable or assessable disease are eligible.
Key exclusion criteria (9 listed)
- Patients who received previous radiotherapy to the brain.
- Patients who received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor. Patients who received Gliadel wafers will be excluded. Patients may have received or be receiving corticosteroids, analgesics, and other drugs to treat symptoms or prevent complications.
- Patients who may be receiving any EIAED (see Appendix C) within 2 weeks prior to registration, or any other prohibited medications within the Washout Period per Appendix D prior to registration. See section 6.5 for seizure medication managements.
- Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
- Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
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 |
|---|---|---|
| Lapatinib/Temozolomide/radiationPatients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression. | Other | Lapatinib/Temozolomide/radiation |
Primary outcome
Overall survival
Time frame: 2 years
The primary objective is to estimate the overall survival in subjects with newly-diagnosed glioblastoma treated with lapatinib/temozolomide/radiation followed by lapatinib/temozolomide for 2 years or until progression is detected. If no progression is seen at 2 years, then single-agent lapatinib will be continued until progression.
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 May 2024.
- Derived from this study: PubMed 28669012Yu A, Faiq N, Green S, Lai A, Green R, Hu J, Cloughesy TF, Mellinghoff I, Nghiemphu PL. Report of safety of pulse dosing of lapatinib with temozolomide and radiation therapy for newly-diagnosed glioblastoma in a pilot phase II study. J Neurooncol. 2017 Sep;134(2):357-362. doi: 10.1007/s11060-017-2533-6. Epub 2017 Jul 1.
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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.
Pioanh Nghiemphu, M D principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lapatinib/Temozolomide/radiation in people with Newly Diagnosed Glioblastoma Multiforme, run by Jonsson Comprehensive Cancer Center at 1 site 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 13 inclusion and 9 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 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Overall 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?
On the ClinicalTrials.gov record for NCT01591577, which also lists 1 linked publication.
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 May 2024.