Working… Menu

Vandetanib and Sirolimus in Patients With Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00821080
Recruitment Status : Completed
First Posted : January 13, 2009
Last Update Posted : May 1, 2015
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Tracy T. Batchelor, MD, Massachusetts General Hospital

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Sirolimus Drug: Vandetanib Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Vandetanib and Sirolimus in Patients With Recurrent Glioblastoma
Study Start Date : October 2008
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Vandetanib and Sirolimus
Single arm study
Drug: Sirolimus
Taken orally at different dose levels depending upon enrollment time period

Drug: Vandetanib
Taken orally at different dose levels depending upon enrollment time period

Primary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00821080

Layout table for location information
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Instiute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Layout table for investigator information
Principal Investigator: Tracy Batchelor, MD Massachusetts General Hospital
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Tracy T. Batchelor, MD, Principal Investigator, Massachusetts General Hospital Identifier: NCT00821080    
Other Study ID Numbers: 07-396
First Posted: January 13, 2009    Key Record Dates
Last Update Posted: May 1, 2015
Last Verified: April 2015
Keywords provided by Tracy T. Batchelor, MD, Massachusetts General Hospital:
recurrent glioblastoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs