Testing the Addition of an Anti-Cancer Drug, Mycophenolate Mofetil, to the Usual Treatment (Radiation Therapy and Temozolomide) for Advanced Brain Cancer
Mycophenolate Mofetil to Overcome Glioblastoma Resistance to Radiotherapy and Temozolomide
調査の概要
状態
条件
詳細な説明
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
I. To compare the overall survival (OS) (phase III) and progression-free survival (PFS) (phase II) between the experimental arm (mycophenolate mofetil [MMF] + standard of care [SOC]) and the control arm (SOC).
SECONDARY OBJECTIVES:
I. To compare the proportion of patients with an objective tumor response (ORR), measured with Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, between the two treatment arms.
II. To determine the adverse event profiles for each arm (using the current latest version of Common Terminology Criteria for Adverse Events [CTCAE]).
III. To determine if there is an association between OS and PFS between treatment arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients under 70 years undergo intensity modulated radiation therapy (IMRT), Monday-Friday for 30 treatments and patients greater than or equal to 70 years undergo hypofractionated radiation therapy, Monday-Friday for 15 treatments in the absence of disease progression or unacceptable toxicity. Starting 24 hours prior to radiation, patients also receive temozolomide orally (PO) once daily (QD) until the day of the last radiation treatment, in the absence of disease progression or unacceptable toxicity. Patients then undergo a 4-week rest period. Patients then receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) and blood sample collection throughout the study.
ARM II: Patients under 70 years undergo IMRT, Monday-Friday for 30 treatments and patients greater than or equal to 70 years undergo hypofractionated radiation therapy, Monday-Friday for 15 treatments in the absence of disease progression or unacceptable toxicity. Starting 24 hours prior to radiation, patients also receive temozolomide PO QD until the day of the last radiation treatment, and, starting on the first day of radiation, patients also receive mycophenolate mofetil PO twice daily (BID) in the absence of disease progression or unacceptable toxicity. Patients then undergo a 4-week rest period. Patients then receive temozolomide PO QD on days 1-5 and mycophenolate mofetil PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 10 weeks until 2 years then every 6 months until 5 years.
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 3
連絡先と場所
研究連絡先
- 名前:Amanda Clark
- 電話番号:(773) 702-9171
- メール:neurooncologyprotocols@alliancenctn.org
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Newly diagnosed primary glioblastoma by World Health Organization (WHO) 2021 criteria
- No spinal cord glioblastoma
- No leptomeningeal disease
- No extracranial metastatic disease
- Patient is a candidate for first-line standard of care chemoradiation per treating physician(s)
- No prior treatment for glioblastoma other than resection (i.e. prior chemotherapy, radiation therapy, or other therapies such as laser ablation are not allowed)
- Prior biopsy and/or resection of glioblastoma must be completed at least 14 days prior to registration with adequate wound healing
- Age ≥ 18 years
- Karnofsky performance status (KPS) ≥ 60
- Absolute neutrophil count (ANC) ≥ 1,500/mm^3
- Platelet count ≥ 100,000 cells/mm^3
- Hemoglobin (Hg) ≥ 9.0 g/dL
Calculated (Calc.) creatinine clearance (CrCl) ≥ 25 mL/min
* Calculated using the Cockcroft-Gault equation
- Bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3.0 x ULN
- Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.
Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 14 days prior to registration is required.
Women and men of reproductive potential must agree to use a highly effective method of birth control throughout their participation in this study and for at least 6 weeks (women) or 90 days (men) after last dose of treatment. Reproductive status and discussions about birth control measures should be documented in the patient's record. Appropriate methods of birth control include, but are not limited to: abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- No known history of allergic reaction or hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA), or any component of the drug product
- No known history of hypersensitivity reactions to temozolomide (TMZ) or other ingredients in TMZ
- No known medical condition causing an inability to swallow oral formulations of agents
- No active systemic or central nervous system (CNS) infection
- No grade 4 lymphopenia (if absolute lymphocyte count [ALC] < 0.5, then patient must be on prophylaxis for Pneumocystis jirovecii)
- No known history of organ transplantation
- No known hypoxanthine-guanine phosphoribosyl-transferase deficiency
- No known serious intercurrent illness that limits participation in the trial
- No known immunosuppressive condition from autoimmune disease, immune deficiency syndrome, or chronic immunosuppressive therapy
- Patient must be able to undergo MRI brain with and without contrast
- No known phenylketonuria
- No known medical contraindication for mycophenolate mofetil (MMF) per treating physician(s)
- Patients on steroids must be on stable or decreasing dose within 7 days of registration (no more than 8 mg dexamethasone/day or equivalent)
Exclusion Criteria:
-
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的:Arm I (radiation, temozolomide)
Patients under 70 years undergo IMRT, Monday-Friday for 30 treatments and patients greater than or equal to 70 years undergo hypofractionated radiation therapy, Monday-Friday for 15 treatments in the absence of disease progression or unacceptable toxicity.
Starting 24 hours prior to radiation, patients also receive temozolomide PO QD until the day of the last radiation treatment, in the absence of disease progression or unacceptable toxicity.
Patients then undergo a 4-week rest period.
Patients then receive temozolomide PO QD on days 1-5 of each cycle.
Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI and blood sample collection throughout the study.
|
MRIを受ける
IMRTを受ける
他の名前:
少分割放射線療法を受ける
与えられたPO
undergo Biospecimen Collection
|
|
実験的:Arm II (radiation, temozolomide, mycophenolate mofetil)
Patients under 70 years undergo IMRT, Monday-Friday for 30 treatments and patients greater than or equal to 70 years undergo hypofractionated radiation therapy, Monday-Friday for 15 treatments in the absence of disease progression or unacceptable toxicity.
Starting 24 hours prior to radiation, patients also receive temozolomide PO QD until the day of the last radiation treatment, and, starting on the first day of radiation, patients also receive mycophenolate mofetil PO twice daily (BID) in the absence of disease progression or unacceptable toxicity.
Patients then undergo a 4-week rest period.
Patients then receive temozolomide PO QD on days 1-5 and mycophenolate mofetil PO BID on days 1-28 of each cycle.
Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI and blood sample collection throughout the study.
|
MRIを受ける
IMRTを受ける
他の名前:
与えられたPO
与えられたPO
undergo Biospecimen Collection
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression free survival (PFS) (phase II)
時間枠:From randomization to the disease progression according to Response Assessment in Neuro-Oncology (RANO) 2.0 criteria or death due to any cause, up to 5 years
|
PFS will be calculated from randomization until disease progression according to RANO 2.0 criteria or death due to any cause, censoring patients at their last disease evaluation.
The Kaplan-Meier method will be used to estimate PFS for each arm and a stratified log-rank test will be used to compare distributions
|
From randomization to the disease progression according to Response Assessment in Neuro-Oncology (RANO) 2.0 criteria or death due to any cause, up to 5 years
|
|
Overall survival (OS) (phase III)
時間枠:From randomization until death due to any cause, up to 5 years
|
OS will be calculated from randomization until death due to any cause, censoring patients at their last disease evaluation.
The Kaplan-Meier method will be used to estimate OS for each arm and a stratified log-rank test will be used to compare distributions.
|
From randomization until death due to any cause, up to 5 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Tumor response
時間枠:Up to 5 years
|
Defined as a complete response or partial response as determined using RANO 2.0.
|
Up to 5 years
|
|
Incidence of adverse events
時間枠:Up to 5 years
|
Determined by the most recent version of Common terminology Criteria for Adverse Events.
|
Up to 5 years
|
|
Overall survival (OS)
時間枠:From randomization until death due to any cause, up to 5 years
|
Kaplan Meier methods will be used to estimate key aspects of the OS distributions for each of the treatment arms, and log rank tests will be used to compare these distributions between arms.
|
From randomization until death due to any cause, up to 5 years
|
|
Progression free survival (PFS)
時間枠:From randomization to the disease progression according to RANO 2.0 criteria or death due to any cause, up to 5 years
|
Kaplan-Meier methods will be used to estimate key aspects of the PFS distributions for each of the treatment arms, and log-rank tests will be used to compare these distributions between arms.
|
From randomization to the disease progression according to RANO 2.0 criteria or death due to any cause, up to 5 years
|
協力者と研究者
捜査官
- スタディチェア:Priya Kumthekar, MD、Alliance for Clinical Trials in Oncology
- スタディチェア:Yoshie Umemura, MD, MS、Alliance for Clinical Trials in Oncology
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- A072402
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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