GlioblastomaPhase 1NCT00821080
Vandetanib and Sirolimus in Patients With Recurrent Glioblastoma
A Phase 1 study testing Sirolimus and Vandetanib in people with Glioblastoma, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
This study is evaluating a combination of drugs called sirolimus and vandetanib to treat glioblastoma. Sirolimus has been approved for use in patients who undergo organ transplants. Sirolimus works by suppressing the immune system so the body will not reject the transplanted organ. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Sirolimus and Vandetanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2008to Feb 2015
- Phase
- Phase 1
- 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
- Histologically confirmed glioblastoma at some point in their disease course
- All patients must have received prior standard therapy including resection if feasible, radiation and temozolomide
- May have received 3 or fewer chemotherapy or biotherapy systemic regimens. Gliadel wafer therapy is not counted as a regimen. Patients may not have received any prior anti-VEGF, anti-EGF therapy or mTOR inhibitors.
- Lab values as outlined in protocol
- Must have recovered from immediate post-operative period and must be maintained on stable or decreasing corticosteroid regimen for at least 3 days prior to the start of treatment
- Must have recovered from possible complications of prior chemotherapies and have a period of 28-42 days since last treatment. Patients must be at least 4 weeks from a non-nitrosourea chemotherapy or 6 weeks from a nitrosourea chemotherapy. Patients must be at least 1 week from the use of non-cytotoxic therapies
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- Must be at least 3 months from the completion of radiation or radiosurgery
- Must have documented progression of the disease on the MRI scan using Macdonald criteria
- KPS 60 or greater
- Mini-Mental Status Examination (MMSE) Score > 15
- 18 years of age or older
- All female participants of childbearing potential must have a negative pregnancy test prior to enrollment
Who cannot join
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
- Clinically significant cardiovascular event within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia
- History of arrhythmia which is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is NOT an exclusion
- Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication
- Congenital QTc syndrome or 1st degree relative with unexplained sudden death under 40 years of age
- Presence of left bundle branch block (LBBB)
Show all 24Show fewer
- QTc with Bazett's correction that is unmeasurable or 480 or greater msec on screening ECG
- Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
- Hypertension not controlled by medical therapy
- Currently active diarrhea that may affect the ability of the patient to absorb the vandetanib. Specifically, patients with diarrhea of CTCAE v3.0 grade III or above will be excluded
- Women who are currently pregnant or breast-feeding
- Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
- Receipt of any investigational agents within 30 days prior to commencing study treatment
- Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy
- Major surgery, including craniotomy for tumor resection, within 4 weeks or incompletely healed surgical incision before starting study therapy. Stereotactic biopsy of the tumor within 2 weeks of starting therapy
- Patients on enzyme-inducing anti-epileptic (EIAED) drug therapy
- Patients unable to undergo MRI evaluation prior to potential enrollment
- Patients who, in the opinion of the treating neuro-oncologist, have a significant intratumoral or peritumoral hemorrhage evident on pre-therapy MRI
- Patients with a history of wound-healing disorders, advanced coronary disease, or with a recent history (<1 year) of peptic ulcer disease
- Patients with serious and chronic liver function abnormalities and uncontrolled hyperlipidemia
- Patients unable to be treated with medications for PCP prophylaxis
- Patients with documented allergy to sirolimus
- Patients who are severely immunosuppressed
- Current anticoagulation is NOT criteria for exclusion
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Instiute
Boston, Massachusetts, 02115
About this study
Official title: A Phase I Study of Vandetanib and Sirolimus in Patients With Recurrent Glioblastoma
This study is evaluating a combination of drugs called sirolimus and vandetanib to treat glioblastoma. Sirolimus has been approved for use in patients who undergo organ transplants. Sirolimus works by suppressing the immune system so the body will not reject the transplanted organ. Vandetanib is an investigational drug and we are trying to find the highest and safest dose of vandetanib with sirolimus that can be given safely.
Read the detailed description
- Vandetanib will be given to participants in tablet form. The dose taken will depend upon when they are enrolled in the study. The doctor will inform them of which dose they are on and how many tablets they will be taking.
- Sirolimus will also be given to participants in tablet form. The dose taken will depend upon when they are enrolled in the study. The dose on the first day will be higher than the dose taken every other day.
- Participants will also be given Bactrim, one double-strength table three times each week (Monday, Wednesday, Friday) to help prevent participants from getting a type of pneumonia called pneumocystis pneumonia.
- The following tests and procedures will be performed before the participants begin taking the study drugs and before every 4 week cycle: Physical exam; medical history; questions about any side effects; tumor assessment by MRI or CT (only before every other cycle); Mini-Mental Status exam (MMSE); ECG (week 1, 2, 4, 8, 12, then every 3 months thereafter); blood pressure; blood tests and urine tests.
- Participants will be in this research study for a maximum of 12 months.
- Conditions
- Glioblastoma
- Being tested
- Sirolimus, Vandetanib
- Keywords
- vandetanib, sirolimus, recurrent glioblastoma
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Taken orally at different dose levels depending upon enrollment time period
VandetanibDrug
Taken orally at different dose levels depending upon enrollment time period
| Study group | Role | What they receive |
|---|---|---|
| Vandetanib and Sirolimus | Experimental | Single arm study Receives: Drug: Sirolimus; Drug: Vandetanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the optimal, safe dose of vandetanib in combination with sirolimus. MTD and dose-limiting toxicity (DLT) of this combination therapy will also be established
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2009 (estimated)
- Study startOct 2008
- Primary completionFeb 2015
- Study completionFeb 2015
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 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Dana-Farber Cancer Institute, AstraZeneca
- Responsible party
- Principal investigator, Tracy T. Batchelor, MD, Massachusetts General Hospital
- Investigators
- Tracy Batchelor, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00821080
- Sponsor's protocol ID
- 07-396
- Status last verified
- Apr 2015
- First submitted
- 9 Jan 2009
- Last updated
- 1 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chheda MG, Wen PY, Hochberg FH, Chi AS, Drappatz J, Eichler AF, Yang D, Beroukhim R, Norden AD, Gerstner ER, Betensky RA, Batchelor TT. Vandetanib plus sirolimus in adults with recurrent glioblastoma: results of a phase I and dose expansion cohort study. J Neurooncol. 2015 Feb;121(3):627-34. doi: 10.1007/s11060-014-1680-2. Epub 2014 Dec 13.
PubMed 25503302
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Vandetanib and Sirolimus in Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT00821080
- Acronym / sponsor ID
- 07-396
- Conditions
- Glioblastoma
- Keywords
- vandetanib, sirolimus, recurrent glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Dana-Farber Cancer Institute, AstraZeneca
- Study start
- Oct 2008
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 13 Jan 2009 (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.
This study is evaluating a combination of drugs called sirolimus and vandetanib to treat glioblastoma. Sirolimus has been approved for use in patients who undergo organ transplants. Sirolimus works by suppressing the immune system so the body will not reject the transplanted organ. Vandetanib is an investigational drug and we are trying to find the highest and safest dose of vandetanib with sirolimus that can be given safely.
Detailed description
- Vandetanib will be given to participants in tablet form. The dose taken will depend upon when they are enrolled in the study. The doctor will inform them of which dose they are on and how many tablets they will be taking.
- Sirolimus will also be given to participants in tablet form. The dose taken will depend upon when they are enrolled in the study. The dose on the first day will be higher than the dose taken every other day.
- Participants will also be given Bactrim, one double-strength table three times each week (Monday, Wednesday, Friday) to help prevent participants from getting a type of pneumonia called pneumocystis pneumonia.
- The following tests and procedures will be performed before the participants begin taking the study drugs and before every 4 week cycle: Physical exam; medical history; questions about any side effects; tumor assessment by MRI or CT (only before every other cycle); Mini-Mental Status exam (MMSE); ECG (week 1, 2, 4, 8, 12, then every 3 months thereafter); blood pressure; blood tests and urine tests.
- Participants will be in this research study for a maximum of 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vandetanib and Sirolimus | Experimental | Drug: Sirolimus, Drug: VandetanibSingle arm study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed glioblastoma at some point in their disease course
- All patients must have received prior standard therapy including resection if feasible, radiation and temozolomide
- May have received 3 or fewer chemotherapy or biotherapy systemic regimens. Gliadel wafer therapy is not counted as a regimen. Patients may not have received any prior anti-VEGF, anti-EGF therapy or mTOR inhibitors.
- Lab values as outlined in protocol
- Must have recovered from immediate post-operative period and must be maintained on stable or decreasing corticosteroid regimen for at least 3 days prior to the start of treatment
Key exclusion criteria (24 listed)
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
- Clinically significant cardiovascular event within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia
- History of arrhythmia which is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is NOT an exclusion
- Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication
- Congenital QTc syndrome or 1st degree relative with unexplained sudden death under 40 years of age
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 |
|---|---|---|
| SirolimusTaken orally at different dose levels depending upon enrollment time period | Drug | Vandetanib and Sirolimus |
| VandetanibTaken orally at different dose levels depending upon enrollment time period | Drug | Vandetanib and Sirolimus |
Primary outcome
To determine the optimal, safe dose of vandetanib in combination with sirolimus. MTD and dose-limiting toxicity (DLT) of this combination therapy will also be established
Time frame: 3 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 1 May 2015.
- Derived from this study: PubMed 25503302Chheda MG, Wen PY, Hochberg FH, Chi AS, Drappatz J, Eichler AF, Yang D, Beroukhim R, Norden AD, Gerstner ER, Betensky RA, Batchelor TT. Vandetanib plus sirolimus in adults with recurrent glioblastoma: results of a phase I and dose expansion cohort study. J Neurooncol. 2015 Feb;121(3):627-34. doi: 10.1007/s11060-014-1680-2. Epub 2014 Dec 13.
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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.
Tracy Batchelor, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sirolimus and Vandetanib in people with Glioblastoma, run by Massachusetts General Hospital at 2 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 12 inclusion and 24 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 1 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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.
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?
To determine the optimal, safe dose of vandetanib in combination with sirolimus. MTD and dose-limiting toxicity (DLT) of this combination therapy will also be established (time frame: 3 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 NCT00821080, 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 1 May 2015.