Vandetanib and Sirolimus in Patients With Recurrent Glioblastoma

NCT00821080 | Completed Phase 1 DMC

• 1 other identifier: 07-396
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

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.

Conditions

Glioblastoma

Keywords

vandetanib; sirolimus; recurrent glioblastoma

Outcome Measures

Primary Outcomes (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

  3 years

Study Arms (1)

Vandetanib and Sirolimus

EXPERIMENTAL

Single arm study

Drug: Sirolimus; Drug: Vandetanib

Interventions

Sirolimus DRUG

Taken orally at different dose levels depending upon enrollment time period

Vandetanib and Sirolimus

Vandetanib DRUG

Taken orally at different dose levels depending upon enrollment time period

Vandetanib and Sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years of age or older
• All female participants of childbearing potential must have a negative pregnancy test prior to enrollment

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Brigham and Women's Hospital: collaborator
• Dana-Farber Cancer Institute: collaborator
• AstraZeneca: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Instiute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 25503302 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Sirolimus; vandetanib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Tracy Batchelor, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2009
• First Posted: January 13, 2009
• Study Start: October 1, 2008
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: May 1, 2015

Record last verified: 2015-04

Locations

US (2)