Glioblastoma MultiformePhase 1/2ZactimaNCT00441142
Zactima With Temodar During Radiation Treatment for Newly Diagnosed Stage IV Brain Tumors
A Phase 1/2 study testing ZD6474, temozolomide and Radiation Therapy in people with Glioblastoma Multiforme and Gliosarcoma, run by Patrick Y. Wen, MD at 7 sites in United States.
Trial summary
Phase I: The purpose of this research study is to determine the safety of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. This agent is investigational for the treatment of glioblastomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Gliosarcoma
- What is being tested?
- ZD6474, temozolomide and Radiation Therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 7 sitesUnited States
- Study dates
- 25 May 2007to 10 Oct 2017
- Phase
- Phase 1/2
- 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
- Subjects with histologically proven intracranial glioblastoma multiforme (GBM) and gliosarcoma will be eligible for this protocol.
- Gadolinium MRI or contrast CT must be obtained within 14 days prior to registration.
- Patients must have a plan to begin treatment with ZD6474 (vandetanib) and/or temozolomide 21 to 35 days after surgical resection or 14 to 35 days after stereotactic biopsy.
- Subjects must have a plan to begin partial brain radiotherapy 5-7 days after beginning ZD6474. Radiotherapy must be a) at the Radiation Oncology Department of the participating institution, b) at an affiliated site that is currently approved to participate in any trial of the Radiation Therapy Oncology Group (RTOG), or c) at another location with prior approval from the Overall PI of the trial. Radiotherapy must be given by external beam to a partial brain field in daily fractions of 180 to 200 cGy, to a planned total dose to the tumor of approximately 6000 cGy. Stereotactic radiosurgery and brachytherapy will not be allowed.
- If it is deemed in the best interest of the patient, intensity modulated radiation therapy (IMRT) is allowable on this trial. If IMRT is administered, dose specifics must be conducted per institutional guidelines.
- Subjects must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with ZD6474 (ZactimaTM), with the exception of temozolomide.
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- All subjects must sign an informed consent indicating that they are aware of the investigational nature of this study prior to any study-related procedures. Patients must be registered with in the Dana Farber Cancer Institute's Quality Assurance Office for Clinical Trials prior to treatment with ZD6474 (Vandetanib). Patients must sign an authorization for the release of their protected health information.
- Subjects can be male or female, and must be >/= 18 years old, with a life expectancy > 12 weeks.
- Subjects must be able to care for themselves (KPS>/=60).
- Subjects must have adequate labs as defined below:
- 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), adequate liver function (SGOT, SGPT </= 2.5 times ULN; bilirubin </= 1.5 times ULN), and adequate renal function (creatinine < 1.5 mg/dL, and/or serum creatinine </= 1.5 x ULN, and/or creatinine clearance > 30 mL/min, calculated by Cockcroft-Gault formula) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
- Patients must have potassium >/= 4.0 mmol/L and serum calcium (ionized or adjusted for albumin) or magnesium in the normal range (supplementation is allowed).
- Patients' alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be </= 2.5 X ULRR and their alkaline phosphatase (ALP) </= 2.5 x ULRR, (or </= 5x ULRR if judged by the investigator to be related to liver metastases)
- Women of childbearing potential must have a negative pregnancy test documented within 14 days prior to registration.
- Men and women of childbearing potential must agree to use adequate contraception while receiving study medication and continue for at least two months (five half-lives) after their last dose of study medication.
- Patients must have sufficient tissue available from their prior biopsy/surgery: at least 10 (preferably 20) unstained slides or 1 tissue block.
- Patients must agree not to donate blood during the trial and for 3 months following their last dose of trial treatment
Who cannot join
- Subjects must not have had prior cranial radiation therapy.
- Subjects must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
- Subjects must not have received prior Gliadel wafers.
- Subjects must not have received any investigational agents within 30 days prior to commencing study treatment
- Subjects must not have evidence of severe or uncontrolled systemic disease or any concurrent condition that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
- Subjects 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.
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- Subjects must not have any unresolved toxicity greater than CTC grade 1 related to previous anti-cancer therapy.
- Subjects must not have active infection.
- Subjects must not be pregnant/breast feeding.
- Subjects must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
- Subjects must not have history of any clinically significant cardiac event, or evidence of heart disease.
- No event such as myocardial infarction or superior vena cava syndrome (SVC); New York Heart Association (NYHA) classification of heart disease >/= 2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
- No history of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
- No previous history of QTc prolongation as a result from other medication that required discontinuation of that medication.
- No congenital long QT syndrome, or1st degree relative with unexplained sudden death under 40 years of age.
- No left bundle branch block (LBBB).
- Subject's screening ECG cannot indicate QTc (with Bazett's correction) that is either unmeasurable or >/= 480 msec on. If subject's screening QTc >/= 480 msec, it may be repeated twice (at least 24 hours apart). The average QTc from the 3 screening ECGs must be < 480 msec. Patients who are receiving a drug that has a risk of inducing Torsades de Pointes are excluded if QTc is >/= 460 msec.
- Subjects must not be taking any enzyme-inducing anti-epileptic drugs (EIAED) or other drugs that are potent inducers of CYP3A4 function (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbitol and St. John's Wort). If patients were previously on EIAEDs and these have been discontinued, patients must have been off the agent for at least 7 days prior to registration.
- Subjects must not be taking concomitant medications known to prolong the QT interval and have a risk of inducing Torsade de Pointes (TdP). Any concurrent medication with a known risk of inducing TdP that, in the investigator's opinion cannot be discontinued, will be allowed; however, these patients must be monitored closely.
- Subjects must not have uncontrolled hypertension (high blood pressure).
- Subjects must not have active diarrhea that may affect the ability of the patient to absorb or tolerate ZD6474 (Vandetanib).
- Subjects with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if he/she feels that 1) a potential drug interaction between ZD6474 (Vandetanib) and any of the patient's anti-HIV medications could influence the efficacy of the anti-HIV medication, or 2) it may place the patient at risk due to the pharmacologic activity of ZD6474 (Vandetanib).
- Subjects' pre-operative MRI must not demonstrate significant intratumoral or peritumoral hemorrhage \& post-operative MRI must not demonstrate a large amount of peri-operative parenchymal hemorrhage. (Patients may have postoperative intracavitary blood.)
- Subjects must not have had major surgery (unrelated to the glioblastoma) within 4 weeks before starting study therapy, and subjects cannot have a surgical incision that has not completely healed before starting study therapy.
- Subjects must not be receiving Coumadin (subjects may take low molecular weight heparin).
- Subjects must not have enrolled on this trial previously.
- Subjects must have had no involvement in the planning or conduct of the study (applies to both AstraZeneca staff or staff at the study site).
- Any of the following lab results will result in patient exclusion from trial:
- Potassium: < 4.0 mmol/L despite supplementation, or above the CTCAE grade 1 upper limit.
- Magnesium below the normal range despite supplementation, or above the CTCAE grade 1 upper limit.
- Serum calcium above the CTCAE grade 1 upper limit.
- NOTE: In cases where the serum calcium is below the normal range, 2 options would be available:
- The calcium adjusted for albumin is to be obtained and substituted for the measured serum value. Exclusion is to then be based on the adjusted for albumin values falling below the normal limit.
- Determine the ionized calcium levels. If these ionized calcium levels are out of normal range despite supplementation, then the patient must be excluded.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber / Brigham and Women's Cancer Center
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of Virginia
Charlottesville, Virginia, 22908-4324
Henry Ford Hospital
Detroit, Michigan, 48202
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232-1305
About this study
Official title: Phase I/II Study of ZD6474 (Vandetanib) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma
Phase I:
The purpose of this research study is to determine the safety of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. This agent is investigational for the treatment of glioblastomas. We will determine the highest dose of ZD6474 (Vandetanib) that can be given safely when combined with temozolomide (Temodar) and radiation therapy.
Read more
Phase II:
The purpose of this research study is to determine the efficacy of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. This agent is investigational for the treatment of glioblastomas.
All subjects participating in this research study must NOT be taking a certain type of anti-seizure medication called enzyme inducing anticonvulsant drugs. These drugs include (but are not limited to) the following medications: Dilantin, Tegretol, Phenobarbital and trileptal.
Read the detailed description
Currently the standard treatment for glioblastomas and gliosarcomas is temozolomide (Temodar) and radiation therapy. This study is being done because research has shown that glioblastomas have genetic changes that may cause an excess of certain cell growth factors and their receptors, which can cause uncontrolled tumor growth. The drug being used in this research study, ZD6474 (Vandetanib), is designed to block the receptors to two of these growth factors, the vascular endothelial growth factor (VEGF) and the epidermal growth factor (EGF). These growth factors are important in pathways that promote tumor growth and increasing blood supply to the tumor. Blocking these receptors may reduce the blood supply to the tumor and help slow down tumor growth. There is also laboratory evidence that blocking these receptors may increase the sensitivity of glioblastomas to radiation therapy.
This research study is a Phase I/II clinical trial.
Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. We will determine the highest dose of ZD6474 (Vandetanib) that can be given safely when combined with temozolomide (Temodar) and radiation therapy.
The purpose of Phase II of this research study is to determine the efficacy of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. It will look to see how patients fare on treatment (if they progress and when, how they are doing after 12 months of treatment). In this research study, the safety of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy will be further evaluated. We will also be looking at samples to see if there are correlations between them and how well patients do on treatment.
This agent is investigational for the treatment of glioblastomas. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. It also means that the FDA (U.S. Food and Drug Administration) has not approved ZD6474 (Vandetanib) for use for your type of cancer. All subjects participating in this research study must NOT be taking a certain type of anti-seizure medication called enzyme inducing anticonvulsant drugs. These drugs include the following medications: Dilantin, Tegretol, Phenobarbital and trileptal.
- Conditions
- Glioblastoma Multiforme, Gliosarcoma
- Being tested
- ZD6474, temozolomide, Radiation Therapy
- Keywords
- Newly diagnosed malignant brain tumors.
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZD6474Drug
Also called Vandetanib, Zactima
Taken orally once a day (at 100 mg/day is the phase II dose; the MTD determined by the phase I portion of the trial) until disease gets worse or participants experience unacceptable side effects
temozolomideDrug
Also called Temodar
During the 'Induction' phase: 75/mg/m2/day temozolomide will be given orally daily for 6 weeks (42 days) during radiation therapy, beginning either the night before or on the first day of the first fraction of radiation, including weekends and holidays. This is followed by a 4-6 week break.
During the 'Maintenance' phase: The first post-radiation temozolomide cycle will be administered at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle. If 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given. This is given for 12 cycles.
Radiation TherapyRadiation
Also called RT, XRT
Radiotherapy must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy.
| Study group | Role | What they receive |
|---|---|---|
| Phase II: Arm A (Control Group: RT + TMZ) | Active comparator | The "Induction" Phase:
Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.
Followed by the "Maintenance" Phase:
12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given]. Receives: Drug: temozolomide; Radiation: Radiation Therapy |
| Phase I + Phase II: Arm B (RT + TMZ + Vandetanib) | Experimental | The "Induction" Phase:
ZD6474 (Vandetanib) daily (to begin 5-7 days prior to starting participant's RT) Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.
Followed by the "Maintenance" Phase:
12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].
ZD6474 (Vandetanib) daily for the twelve (12) 28-day cycles of adjuvant temozolomide, with the option to continue until participant experiences an unacceptable toxicity or his/her tumor progresses. Receives: Drug: ZD6474; Drug: temozolomide; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Experienced a Dose-limiting Toxicity (DLT)
The primary outcome of Phase I of this trial was to determine the maximum tolerated dose (MTD) of ZD6474 (Vandetanib) in patients with newly-diagnosed glioblastomas multiforme (GBM) and gliosarcomas who are also receiving radiation therapy with concomitant and adjuvant temozolomide. The MTD is the dose level at which 0/6 or 1/6 patients experience a dose-limiting toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 patients encountering DLT.
Measured: 2 years
Median Overall Survival (OS) of Phase II Patients
The primary outcome of Phase II of this trial was to determine the efficacy of ZD6474 (Vandetanib) in combination with radiation therapy and concomitant and adjuvant temozolomide in patients with newly-diagnosed GBM and gliosarcomas as measured by overall survival and median survival.
Measured: 3 years
Secondary outcomes (3)
Median Progression-free Survival (PFS), as Calculated by the # of Months Patients Remain Progression-free
A secondary outcome of Phase II of this trial is the median progression-free survival (PFS), as calculated by the # of months patients remain progression-free
Measured: 3 years
PHASE II: Percentage of Grade 3-5 Treatment-Related Adverse Events
The percentage of adverse events (based on CTCAEv3) reported on study (via case report forms and Reportable AE submissions) that are both high-grade (grade 3, 4, or 5) and considered at least possibly related to study treatment.
Measured: Adverse events experienced by participants are collected and reported throughout treatment with study drug (from initiation of study treatment until 30 days after the last dose of study treatment), maximum timeframe was 6 years.
PHASE I: Percentage of Grade 3-5 Treatment-Related Adverse Events
The percentage of adverse events (based on CTCAEv3) reported on study (via case report forms and Reportable AE submissions) that are both high-grade (grade 3, 4, or 5) and considered at least possibly related to study treatment.
Measured: Adverse events experienced by participants are collected and reported throughout treatment with study drug (from initiation of study treatment until 30 days after the last dose of study treatment), maximum timeframe was 7 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2007 (estimated)
- Study start25 May 2007
- Primary completion31 Aug 2013
- Study completion10 Oct 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 Glioblastoma MultiformeStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Patrick Y. Wen, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, University of Virginia, Memorial Sloan Kettering Cancer Center, Henry Ford Hospital
- Responsible party
- Sponsor-investigator, Patrick Y. Wen, MD, Dana-Farber/Brigham and Women's Cancer Center
- Investigators
- Patrick Y Wen, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441142
- Sponsor's protocol ID
- 06-377
- Other IDs
- IRUSZACT0018
- Acronym
- Zactima
- Status last verified
- Feb 2019
- First submitted
- 27 Feb 2007
- Last updated
- 5 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of ZD6474 (Vandetanib) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT00441142
- Acronym / sponsor ID
- Zactima / 06-377
- Conditions
- Glioblastoma Multiforme, Gliosarcoma
- Keywords
- Newly diagnosed malignant brain tumors.
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- Patrick Y. Wen, MDUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, University of Virginia, Memorial Sloan Kettering Cancer Center, Henry Ford Hospital
- Study start
- 25 May 2007 (actual)
- Primary completion
- 31 Aug 2013 (actual)
- Study completion
- 10 Oct 2017 (actual)
- First posted
- 28 Feb 2007 (estimated)
- Results
- Posted 2 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I:
The purpose of this research study is to determine the safety of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. This agent is investigational for the treatment of glioblastomas. We will determine the highest dose of ZD6474 (Vandetanib) that can be given safely when combined with temozolomide (Temodar) and radiation therapy.
Phase II:
The purpose of this research study is to determine the efficacy of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. This agent is investigational for the treatment of glioblastomas.
All subjects participating in this research study must NOT be taking a certain type of anti-seizure medication called enzyme inducing anticonvulsant drugs. These drugs include (but are not limited to) the following medications: Dilantin, Tegretol, Phenobarbital and trileptal.
Detailed description
Currently the standard treatment for glioblastomas and gliosarcomas is temozolomide (Temodar) and radiation therapy. This study is being done because research has shown that glioblastomas have genetic changes that may cause an excess of certain cell growth factors and their receptors, which can cause uncontrolled tumor growth. The drug being used in this research study, ZD6474 (Vandetanib), is designed to block the receptors to two of these growth factors, the vascular endothelial growth factor (VEGF) and the epidermal growth factor (EGF). These growth factors are important in pathways that promote tumor growth and increasing blood supply to the tumor. Blocking these receptors may reduce the blood supply to the tumor and help slow down tumor growth. There is also laboratory evidence that blocking these receptors may increase the sensitivity of glioblastomas to radiation therapy.
This research study is a Phase I/II clinical trial.
Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. We will determine the highest dose of ZD6474 (Vandetanib) that can be given safely when combined with temozolomide (Temodar) and radiation therapy.
The purpose of Phase II of this research study is to determine the efficacy of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. It will look to see how patients fare on treatment (if they progress and when, how they are doing after 12 months of treatment). In this research study, the safety of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy will be further evaluated. We will also be looking at samples to see if there are correlations between them and how well patients do on treatment.
This agent is investigational for the treatment of glioblastomas. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. It also means that the FDA (U.S. Food and Drug Administration) has not approved ZD6474 (Vandetanib) for use for your type of cancer. All subjects participating in this research study must NOT be taking a certain type of anti-seizure medication called enzyme inducing anticonvulsant drugs. These drugs include the following medications: Dilantin, Tegretol, Phenobarbital and trileptal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase II: Arm A (Control Group: RT + TMZ) | Active comparator | Drug: temozolomide, Radiation: Radiation TherapyThe "Induction" Phase: Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest. Followed by the "Maintenance" Phase: 12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given]. |
| Phase I + Phase II: Arm B (RT + TMZ + Vandetanib) | Experimental | Drug: ZD6474, Drug: temozolomide, Radiation: Radiation TherapyThe "Induction" Phase: ZD6474 (Vandetanib) daily (to begin 5-7 days prior to starting participant's RT) Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest. Followed by the "Maintenance" Phase: 12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given]. ZD6474 (Vandetanib) daily for the twelve (12) 28-day cycles of adjuvant temozolomide, with the option to continue until participant experiences an unacceptable toxicity or his/her tumor progresses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Subjects with histologically proven intracranial glioblastoma multiforme (GBM) and gliosarcoma will be eligible for this protocol.
- Gadolinium MRI or contrast CT must be obtained within 14 days prior to registration.
- Patients must have a plan to begin treatment with ZD6474 (vandetanib) and/or temozolomide 21 to 35 days after surgical resection or 14 to 35 days after stereotactic biopsy.
- Subjects must have a plan to begin partial brain radiotherapy 5-7 days after beginning ZD6474. Radiotherapy must be a) at the Radiation Oncology Department of the participating institution, b) at an affiliated site that is currently approved to participate in any trial of the Radiation Therapy Oncology Group (RTOG), or c) at another location with prior approval from the Overall PI of the trial. Radiotherapy must be given by external beam to a partial brain field in daily fractions of 180 to 200 cGy, to a planned total dose to the tumor of approximately 6000 cGy. Stereotactic radiosurgery and brachytherapy will not be allowed.
- If it is deemed in the best interest of the patient, intensity modulated radiation therapy (IMRT) is allowable on this trial. If IMRT is administered, dose specifics must be conducted per institutional guidelines.
Key exclusion criteria (34 listed)
- Subjects must not have had prior cranial radiation therapy.
- Subjects must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
- Subjects must not have received prior Gliadel wafers.
- Subjects must not have received any investigational agents within 30 days prior to commencing study treatment
- Subjects must not have evidence of severe or uncontrolled systemic disease or any concurrent condition that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
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 |
|---|---|---|
| ZD6474Also: Vandetanib, ZactimaTaken orally once a day (at 100 mg/day is the phase II dose; the MTD determined by the phase I portion of the trial) until disease gets worse or participants experience unacceptable side effects | Drug | Phase I + Phase II: Arm B (RT + TMZ + Vandetanib) |
| temozolomideAlso: TemodarDuring the 'Induction' phase: 75/mg/m2/day temozolomide will be given orally daily for 6 weeks (42 days) during radiation therapy, beginning either the night before or on the first day of the first fraction of radiation, including weekends and holidays. This is followed by a 4-6 week break. During the 'Maintenance' phase: The first post-radiation temozolomide cycle will be administered at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle. If 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given. This is given for 12 cycles. | Drug | Phase I + Phase II: Arm B (RT + TMZ + Vandetanib), Phase II: Arm A (Control Group: RT + TMZ) |
| Radiation TherapyAlso: RT, XRTRadiotherapy must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy. | Radiation | Phase I + Phase II: Arm B (RT + TMZ + Vandetanib), Phase II: Arm A (Control Group: RT + TMZ) |
Primary outcome
Number of Participants That Experienced a Dose-limiting Toxicity (DLT)
Time frame: 2 years
The primary outcome of Phase I of this trial was to determine the maximum tolerated dose (MTD) of ZD6474 (Vandetanib) in patients with newly-diagnosed glioblastomas multiforme (GBM) and gliosarcomas who are also receiving radiation therapy with concomitant and adjuvant temozolomide. The MTD is the dose level at which 0/6 or 1/6 patients experience a dose-limiting toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 patients encountering DLT.
Median Overall Survival (OS) of Phase II Patients
Time frame: 3 years
The primary outcome of Phase II of this trial was to determine the efficacy of ZD6474 (Vandetanib) in combination with radiation therapy and concomitant and adjuvant temozolomide in patients with newly-diagnosed GBM and gliosarcomas as measured by overall survival and median survival.
3 secondary outcomes
Median Progression-free Survival (PFS), as Calculated by the # of Months Patients Remain Progression-free
Time frame: 3 years
PHASE II: Percentage of Grade 3-5 Treatment-Related Adverse Events
Time frame: Adverse events experienced by participants are collected and reported throughout treatment with study drug (from initiation of study treatment until 30 days after the last dose of study treatment), maximum timeframe was 6 years.
PHASE I: Percentage of Grade 3-5 Treatment-Related Adverse Events
Time frame: Adverse events experienced by participants are collected and reported throughout treatment with study drug (from initiation of study treatment until 30 days after the last dose of study treatment), maximum timeframe was 7 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
- 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.
Patrick Y Wen, MD principal investigator
Dana-Farber Cancer Institute
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ZD6474, temozolomide and Radiation Therapy in people with Glioblastoma Multiforme and Gliosarcoma, run by Patrick Y. Wen, MD at 7 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 17 inclusion and 34 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 5 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 2 Mar 2015). 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?
Number of Participants That Experienced a Dose-limiting Toxicity (DLT) (time frame: 2 years). The study lists 2 primary outcomes in all. 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 5 Mar 2019.