Phase 2 Completed N=112 Randomized Treatment

A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas

Glioblastoma multiforme · Gliosarcoma · Anaplastic Astrocytoma · Brain Cancer

Source: ClinicalTrials.gov NCT00995007 ↗

Enrolled (actual)

112

Serious AEs

28.6%

Results posted

Mar 2016

Primary outcomePrimary: Progression Free Survival at 6 Months — 1.71; 0.89; 8.7; 17.4 percentage of participants

Summary

Background: * Growth of new blood vessels (angiogenesis) provides many tumors, including brain tumors, with needed nutrients and oxygen for cancer cells to survive. One possible treatment for different kinds of cancer involves treatment with drugs that slow or stop angiogenesis and prevent further tumor growth. * Vandetanib is an oral medication known to block angiogenesis and has shown significant antitumor activity in laboratory and animal studies. Vandetanib appears to be well tolerated by patients at specific daily doses. * Carboplatin is a drug that interrupts division of cancer cells and has been shown to be a useful drug in treatment of tumors known as gliomas. It is a useful drug for treating brain tumors, but researchers are interested in gathering more information about how it works as a treatment for patients who have not responded to initial surgery, radiation, or chemotherapy. Objective: - To determine the safety and effectiveness of vandetanib and carboplatin, given together or sequentially, against recurrent high-grade gliomas. Eligibility: - Adults diagnosed with a malignant glioma who have received standard treatments that no longer appear to be effective. Design: * Patients will be assigned to one of two groups. Group 1 patients (combination group) will receive oral vandetanib for 28 days and intravenous (IV) carboplatin (once at the beginning of the 28-day cycle). Group 2 patients (sequential group) will receive IV carboplatin alone (once at the beginning of the 28-day cycle) and then oral vandetanib (300 mg daily) for 28 days if the tumor grows or the patient develops unacceptable carboplatin toxicity. * Treatment will continue in 28-day cycles for 1 year for both groups. * Patients will undergo a number of tests and procedures during the treatment cycle, including physical examinations, routine laboratory tests, electrocardiograms, and magnetic resonance imaging (MRI) scans * At the end of 1 year of treatment, patients will be reevaluated for possible continuation of drug therapy.

Outcome Measures

Outcome	Result	p-value
PRIMARY Progression Free Survival at 6 Months	1.71; 0.89; 8.7; 17.4	—
SECONDARY Overall Survival	5.58; 5.22; 6.5; 9.27	—
SECONDARY Number of Participants With Adverse Events	55; 56; 40	—

Eligibility Criteria

INCLUSION CRITERIA:

Patients with histologically proven malignant primary gliomas who have progressive disease after radiotherapy will be eligible for this protocol. These include glioblastoma multiforme (GBM), gliosarcoma, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), and malignant glioma/astrocytoma NOS.

Patients must have an magnetic resonance imaging (MRI)/computed tomography (CT) scan performed within 14 days prior to registration and on a fixed dose of steroids for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MRI/CT is required. The same type of scan, that is, MRI or CT must be used throughout the period of protocol treatment for tumor measurement.

Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:

Patients will be eligible four weeks after surgery if they have recovered from the effects of surgery.

Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/MRI should be done:

no later than 96 hours in the immediate post-operative period or
at least 4 weeks post-operatively, and
within 14 days of registration, and
on a steroid dosage that has been stable for at least 5 days.

If the 96 hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.

Patients must have failed prior radiation therapy.

All patients or their previously designated durable power of attorney (DPA) (if the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study.

Patients must be greater than or equal to 18 years old, and must have a life expectancy greater than 8 weeks.

Patients must have a Karnofsky performance status of greater than or equal to 60.

Patients must be at least six weeks from radiation therapy. Additionally, patients must be at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from procarbazine, and 2 weeks from last vincristine administration. Patients must be at least 4 weeks from other cytotoxic therapies not listed above and 2 weeks for non-cytotoxic agents (e.g., interferon, tamoxifen) including investigative agents.

Patients must have adequate bone marrow function (white blood cell (WBC) greater than or equal to 3,000/microL, absolute neutrophil count (ANC) greater than or equal to 1,500/mm(3), platelet count of greater than or equal to 100,000/mm(3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase 2.5 less than or equal to upper limit of normal (ULN) and bilirubin less than or equal to 1.5 times ULN), and adequate renal function (creatinine less than or equal to 1.5 mg/dL and/or creatinine clearance greater than or equal to 60 cc/min) before starting therapy. Patients must also have serum potassium greater than or equal to 3.5 mg/dL, magnesium greater than or equal to 0.75 mmol/L and calcium levels within normal levels; supplementation is allowed. In cases where the serum calcium is below the normal range, 2 options would be available: 1) 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. 2) Determine the ionized calcium levels. Exclusion is then to be based if these ionized calcium levels are out of

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Data sourced from ClinicalTrials.gov (NCT00995007). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.