Advertisement

Topics

Temozolomide and Radiation Therapy With or Without Vatalanib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

2014-08-27 03:52:35 | BioPortfolio

Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Vatalanib may stop the growth of tumor cells by blocking blood flow to the tumor. Giving temozolomide and radiation therapy together with vatalanib may kill more tumor cells.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of vatalanib when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme.

Description

OBJECTIVES:

Primary

- Determine the maximum tolerated dose and recommended phase II dose of vatalanib when given in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma multiforme. (Phase I)

- Determine the safety and tolerability of this regimen in these patients. (Phase I)

- Determine the 6-month progression-free survival of patients treated with chemoradiotherapy comprising temozolomide and radiotherapy with or without vatalanib followed by adjuvant therapy comprising temozolomide and vatalanib or temozolomide alone with or without maintenance therapy comprising vatalanib alone. (Phase II)

Secondary

- Determine 12-month overall survival of patients treated with these regimens. (Phase II)

- Determine the toxicity profile of these regimens in these patients. (Phase II)

- Correlate expression of angiogenesis and hypoxia markers and MGMT methylation status with clinical outcome in patients treated with these regimens.

OUTLINE: This is a phase I, multicenter, open-label, non-randomized, dose-escalation study of vatalanib followed by a phase II, randomized, controlled study. Patients enrolled in the phase II portion of the study are stratified according to participating center, age (< 50 years vs ≥ 50 years), corticosteroid intake (yes vs no), and mini-mental status evaluation score (< 27 vs 27-29 vs 30).

- Phase I:

- Chemoradiotherapy: Patients receive oral temozolomide once daily for 6-7 weeks and oral vatalanib once daily for 6 weeks. Patients also undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients continue to receive oral vatalanib twice daily.

Cohorts of 3-6 patients receive escalating doses of vatalanib during chemoradiotherapy until the maximum tolerated dose is determined (MTD). The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

- Adjuvant therapy: Patients receive oral temozolomide once daily on days 1-5 and oral vatalanib twice daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance therapy.

- Maintenance therapy: Patients continue to receive oral vatalanib twice daily in the absence of disease progression or unacceptable toxicity.

- Phase II: Patients are randomized to 1 of 3 treatment arms.

- Arm I:

- Chemoradiotherapy: Patients receive oral temozolomide once daily for 6-7 weeks and undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy.

- Adjuvant therapy: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

- Arm II:

- Chemoradiotherapy: Patients receive temozolomide and undergo radiotherapy as in arm I. Patients also receive vatalanib twice daily for 6 weeks at the MTD determined in phase I. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients continue to receive oral vatalanib twice daily.

- Adjuvant therapy: Patients receive temozolomide and vatalanib as in phase I adjuvant therapy. Patients then proceed to maintenance therapy.

- Maintenance therapy: Patients continue to receive vatalanib as in phase I maintenance therapy.

- Arm III:

- Chemoradiotherapy: Patients receive temozolomide and undergo radiotherapy as in arm I. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients receive oral vatalanib twice daily.

- Adjuvant therapy: Patients receive temozolomide and vatalanib as in phase I adjuvant therapy. Patients then proceed to maintenance therapy.

- Maintenance therapy: Patients continue to receive vatalanib as in phase I maintenance therapy.

After completion of study treatment, patients are followed every 3 months for survival.

PROJECTED ACCRUAL: Approximately 3-18 patients will be accrued for the phase I portion of this study. A total of 201 patients (67 per treatment arm) will be accrued for the phase II portion of this study.

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Conditions

Brain and Central Nervous System Tumors

Intervention

temozolomide, vatalanib, adjuvant therapy, radiation therapy

Location

U.Z. Gasthuisberg
Leuven
Belgium
B-3000

Status

Completed

Source

European Organisation for Research and Treatment of Cancer - EORTC

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:52:35-0400

Clinical Trials [6107 Associated Clinical Trials listed on BioPortfolio]

Temozolomide and Radiation Therapy in Treating Patients With Gliomas

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiat...

Radiation Therapy or Radiation Therapy and Temozolomide or Temozolomide Alone in Treating Patients With Newly Diagnosed Anaplastic Glioma

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either...

Radiation Therapy or Temozolomide in Treating Patients With Gliomas

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either...

Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor...

Radiation Therapy Plus Thalidomide and Temozolomide in Treating Patients With Newly Diagnosed Brain Metastases

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Tha...

PubMed Articles [23387 Associated PubMed Articles listed on BioPortfolio]

Good tolerability of maintenance temozolomide in glioblastoma patients after severe hematological toxicity during concomitant radiotherapy and temozolomide treatment: report of two cases.

Glioblastoma is the most common and aggressive primitive brain tumor in adults. Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ has become the standard treatment...

Outcomes in real-world practice are different than cooperative trial for elderly patients with early breast cancer treated with adjuvant radiation therapy.

The Cancer and Leukemia Group B 9,343 demonstrated that postoperative radiation can be safely omitted in women ≥70 years who underwent breast-conserving therapy for clinical stage I (T1N0M0) estroge...

Assessment of radiation resistance and therapeutic targeting of cancer stem cells: A Raman spectroscopic study of Glioblastoma.

Radiation is the standard therapy used for treating Glioblastoma (GBM), a grade IV brain cancer. Glioma Stem-like Cells (GSCs), an integral part of GBM enforces resistance to radiation therapy of GBM....

Objective assessment of flap volume changes and aesthetic results after adjuvant radiation therapy in patients undergoing immediate autologous breast reconstruction.

The use of immediate breast reconstruction and adjuvant radiation therapy is increasing in breast cancer patients. This study aimed to analyze the aesthetic outcome and changes in flap volume in patie...

Radiation-Induced Gliomas.

Radiation therapy has been a cornerstone of cancer management for many decades and is an integral part of the multi-modality care of patients with brain tumors. The known serious side effects of radia...

Medical and Biotech [MESH] Definitions

Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.

Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment.

A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases.

Organs which might be damaged during exposure to a toxin or to some form of therapy. It most frequently refers to healthy organs located in the radiation field during radiation therapy.

Radiotherapy given to augment some other form of treatment such as surgery or chemotherapy. Adjuvant radiotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.

More From BioPortfolio on "Temozolomide and Radiation Therapy With or Without Vatalanib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...


Searches Linking to this Trial