Zactima With Temodar During Radiation Treatment for Newly Diagnosed Stage IV Brain Tumors

NCT00441142 | Completed Phase 1 Results DMC

• 2 other identifiers: 06-377IRUSZACT0018
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 7

Brief 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. 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.

Conditions

Glioblastoma Multiforme; Gliosarcoma

Keywords

Newly diagnosed malignant brain tumors.

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  3 years

Secondary Outcomes (3)

• Median Progression-free Survival (PFS), as Calculated by the # of Months Patients Remain Progression-free

  3 years

• PHASE II: Percentage of Grade 3-5 Treatment-Related Adverse Events

  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

  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.

Study Arms (2)

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 \[at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given\].

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.

Drug: ZD6474; Drug: temozolomide; Radiation: Radiation Therapy

Interventions

ZD6474 DRUG

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

Also known as: Vandetanib, Zactima

Phase I + Phase II: Arm B (RT + TMZ + Vandetanib)

temozolomide DRUG

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.

Also known as: Temodar

Phase I + Phase II: Arm B (RT + TMZ + Vandetanib); Phase II: Arm A (Control Group: RT + TMZ)

Radiation Therapy RADIATION

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.

Also known as: RT, XRT

Phase I + Phase II: Arm B (RT + TMZ + Vandetanib); Phase II: Arm A (Control Group: RT + TMZ)

Eligibility Criteria

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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Patrick Y. Wen, MD: lead
• Dana-Farber Cancer Institute: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Massachusetts General Hospital: collaborator
• University of Virginia: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• Henry Ford Hospital: collaborator

Study Sites (7)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber / Brigham and Women's Cancer Center

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232-1305, United States

Location

University of Virginia

Charlottesville, Virginia, 22908-4324, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

vandetanib; Temozolomide; Radiotherapy

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Results Point of Contact

• Title: Dr. Eudocia Quant Lee
• Organization: Dana-Farber Cancer Institute

eqlee@partners.org

617-632-2166

Study Officials

• Patrick Y Wen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Center For Neuro-Oncology

Study Record Dates

• First Submitted: February 27, 2007
• First Posted: February 28, 2007
• Study Start: May 25, 2007
• Primary Completion: August 31, 2013
• Study Completion: October 10, 2017
• Last Updated: March 5, 2019
• Results First Posted: March 2, 2015

Record last verified: 2019-02

Locations

US (7)