Astrocytoma Clinical Trial
Official title:
A Prospective Cohort to Study the Effect of Postoperative Upfront Temozolomide Chemotherapy on IDH Mutational Low Grade Gliomas in Eloquent Areas
Verified date | February 2019 |
Source | Huashan Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Low grade gliomas (LGGs) are the most common primary central nervous system malignancies.
Brain surgeries with the most possible extent of resection are endeavored to achieve longer
survivals in LGG patients. For patients with tumor located in eloquent areas so that gross
total resection is not applicable, National Comprehensive Cancer Network (NCCN) 2013
guidelines assigned both radiotherapy or chemotherapy as adjuvant treatments of low grade
glioma following surgeries. Retrospective studies have suggested that temozolomide (an oral
chemotherapeutics) chemotherapy have good effects on the control of tumor progression or
recurrence in LGG patients after surgeries, especially in those with isocitrate dehydrogenase
(IDH) gene mutations.
Therefore, our prospective cohort study is to provide a higher level(IIb) of evidence for the
correlation between IDH mutation and the responsiveness to up-front adjuvant metronomic
temozolomide chemotherapy in young patients with LGG located in eloquent brain areas. And
hopefully justify future RCTs with comparison between effects of adjuvant radiotherapy and
chemotherapy in these patients.
Status | Active, not recruiting |
Enrollment | 54 |
Est. completion date | May 2019 |
Est. primary completion date | April 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 40 Years |
Eligibility |
Inclusion Criteria: - 18 years < age = 40 years, both genders. - No neurologic cognitive deficits (MMSE = 27), no psychiatric abnormalities before surgery, pre-operative KPS = 80. - Tumors located in eloquent areas or deeply located nuclei, rendering radiological complete resection inapplicable, according to updated standards of extent of resection: as for non-enhancing LGG, postoperative MRI within 72h shows absence of any preoperative T2/FLAIR signal changes - complete resection; and for enhancing LGG, postoperative MRI shows total removal of preoperative enhancing tissue - complete resection of enhancing tumor; and total removal of enhancing and non-enhancing tissues (T2/FLAIR) - complete resection of detectable tumor. - Post-operative histological pathology confirms LGGs (astrocytomas, oligodendrogliomas, or oligoastrocytomas, 2007 WHO classification Grade II). - No contraindications to TMZ chemotherapy. - Informed consent to TMZ chemotherapy. Exclusion Criteria: - Tumor involves more than 3 cerebral lobes (gliomatosis or multiple gliomas). - Tumor is complicated with other intracranial neoplasms (e.g. metastatic tumors or meningiomas). - Tumor is complicated with systematic malignancies. - Dysfunctions of other vital organs: liver and kidney (ALT?40U/L, AST > 40U/L, creatinine > 97-106µmol/L, urea nitrogen > 7.1mmol/L, or other lab abnormalities); Heart (NYHA II-IV); Lungs (hypoxemia). - Physiological pregnancy. - Participate in other clinical trials at meantime. - History of severe anaphylaxis. - Voluntarily quit or decline chemotherapy. |
Country | Name | City | State |
---|---|---|---|
China | Huashan Hospital Affiliated to Fudan University | Shanghai | Shanghai |
Lead Sponsor | Collaborator |
---|---|
Huashan Hospital |
China,
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E. Mandonnet et al. Toward the Definition of New Endpoints. H. Duffau (ed.), Diffuse Low-Grade Gliomas in Adults, DOI 10.1007/978-1-4471-2213-5_29, Springer-Verlag London 2013
Houillier C, Wang X, Kaloshi G, Mokhtari K, Guillevin R, Laffaire J, Paris S, Boisselier B, Idbaih A, Laigle-Donadey F, Hoang-Xuan K, Sanson M, Delattre JY. IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology. 2010 Oct 26;75(17):1560-6. doi: 10.1212/WNL.0b013e3181f96282. — View Citation
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Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol. 2009 Sep 1;27(25):4150-4. doi: 10.1200/JCO.2009.21.9832. Epub 2009 Jul 27. — View Citation
van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang-Xuan K, Malmström PO, Collette L, Piérart M, Mirimanoff R, Karim AB; EORTC Radiotherapy and Brain Tumor Groups and the UK Medical Research Council. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet. 2005 Sep 17-23;366(9490):985-90. Erratum in: Lancet. 2006 Jun 3;367(9525):1818. — View Citation
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Objective Response Rate, ORR | According to the revised RANO criteria (M J van den Bent, et al. 2011), compared to residual tumor volume calculated with iMRI T2/Flair right after surgery and before up-front adjuvant chemotherapy (Baseline tumor volume): Complete response (CR): disappearance of abnormality Partial response (PR): no less than 50% reduction Minimal response (MR): no less than 25% but less than 50% reduction Stable disease (SD): less than 25% reduction also less than 25% increase Progressive disease (PD): no less than 25% increase Enhanced T1-weighted imaging, magnetic resonance spectroscopy (MRS), Diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) will also be utilized to detect progressions. |
Within 72 hours after surgery, at the beginning of chemotherapy, every 2 months thereafter up to a year, every 3-6 months after a year, until the first documented progression or date of death from any cause, whichever came first, up to 2 years. | |
Primary | Velocity of Diameter Evolution, VDE | According to the Definition of New Endpoints by E. Mandonnet et al, 2013, VDE is calculated with formula D = (2 × V)^1/3, (V= tumor volume). Uncontrolled: unchanged or increased VDE compared to baseline VDE. Slowed down: decreased VDE compared to baseline VDE, but still positive. Stabilized: VDE is close to 0 mm/year. Reversed: negative VDE. Treatment escape and relapse: re-growth of the tumor greater than 2 mm, during the course of chemotherapy and after the end of chemotherapy, respectively. Intensity of response (IOR): how much the diameter has been reduced by the therapy. Duration of response (DOR): the time period between treatment onset and treatment escape or relapse. If Replapse (25% increase/VDE>2mm/Maligmant enhancement), start 2° treatment: Second surgery or radiotherapy or salvage chemotherapy |
Within 72 hours after surgery, at the beginning of chemotherapy, every 2 months thereafter up to a year, every 3-6 months after a year, until the first documented progression or date of death from any cause, whichever came first, up to 2 years. | |
Secondary | Progression free survival (PFS)-6, -12, -24 | The survival rate of followed patients without progressive disease (PD) 6, 12, and 24 months after the 1st cycle of chemotherapy | 6, 12 and 24 months after the 1st cycle of chemotherapy | |
Secondary | Cognitive functions | Test battery: Measured with Minimal Mental State Examination (MMSE); Hopkins verbal learning test-revised; Trail making test, part A and B; Multilingual aphasia examination controlled oral word association |
At the beginning of chemotherapy, every 2 months thereafter up to a year, and every 3-6 months after a year of follow-up, until the first documented (malignant) progression or date of death from any cause, whichever came first, up to 2 years. | |
Secondary | Quality of life (QoL) | Measured with EORTC QLQ-C30 and EORTC-BN20. Duration of response with good quality of life is defined as Time with good quality of life (TQL). | At the beginnning of chemotherapy, every 2 months thereafter up to a year, and every 3-6 months after a year of follow-up, until the first documented (malignant) progression or date of death from any cause, whichever came first, up to 2 years. | |
Secondary | Adverse effect of chemotherapy | Blood routine and kidney/liver functions | At the beginning of chemotherapy, every 2 months thereafter up to a year, until the first documented (malignant) progression or date of death from any cause, whichever came first, up to 2 years. | |
Secondary | Malignant progression-free survival (MPFS) -6, -12, -24 | The survival rate of followed patients without any MRI T1 enhancing signals in 6, 12, and 24 months after the 1st cycle of chemotherapy | 6, 12 and 24 months after the 1st cycle of chemotherapy | |
Secondary | Symptom Burden | Measured with M.D. Anderson Symptom Inventory Brain Tumor Module, MDASI-BT. | At the beginning of the chemotherapy, every 2 months thereafter up to a year, then every 3 months up to 2 years | |
Secondary | Seizure activity | Measured by one neurologist, number and type of seizure and medication in the past month before each follow-up visit are recorded. | At the beginning of the chemotherapy, every 2 months thereafter up to a year, then every 3 months up to 2 years |
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