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出境医 / 临床实验 / First-line Chemotherapy With Temozolomide Alone for Non-enhancing Adult Brainstem Gliomas, With a Diffuse Subtype and Showing Clinical and/or Radiological Infiltrative Pattern of Progression (TEMOTRAD01)
First-line Chemotherapy With Temozolomide Alone for Non-enhancing Adult Brainstem Gliomas, With a Diffuse Subtype and Showing Clinical and/or Radiological Infiltrative Pattern of Progression (TEMOTRAD01)
Study Description
Brief Summary:
This phase 2 study is a prospective cohort study. Chemotherapy alone will be proposed to adult patients suffering from a "low grade" brainstem glioma subtype showing infiltrative, non-threatening clinico-radiological progression. Patients will receive temozolomide at a monthly standard dose of 150-200 mg/m2/j J1-J5, will be clinically evaluated every month and will undergo radiological evaluation every 2 months. The duration of treatment will be 12 months. Then, the patients will be followed-up until progression, with clinical evaluations and MRI performed every 2-3 months. At the time of recurrence, treatment with focal radiation therapy will be administered (54 Gy in classical fractions).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adult Brainstem Glioma | Drug: Temozolomide | Phase 2 |
Detailed Description:
The goal of this study is to assess the impact (objective response) of first-line chemotherapy in infiltrative non-enhancing adult brainstem gliomas that are progressing in an infiltrative and non-threatening way. Upon progression, (radiotherapy) RT will be administered. Main inclusion criteria are:18 years of age or older/Karnofsky's Index over 50 /Non-enhancing lesion at MRI/Histologically proven infiltrating pattern of brainstem glioma except in case of formal contraindication to surgery determined via discussion of the case with expert neurosurgeons during a national webmeeting ((GLIome du TRonc de l'ADulte group (GLITRAD))/Clinical and/or radiological progression with an infiltrative but non-threatening pattern, warranting antitumoral treatment. The treatment delivered will be Temozolomide at a monthly standard dose of 150-200 mg/m2/day at day 1 to day 5 for a duration of treatment of 12 months. The study is a prospective single-arm phase II trial. Primary end point is objective response rate (radiographic and clinical response) to Temozolomide according to Response assessment in neuro-oncology criteria (RANO criteria). Secondary end points are histological pattern of adult brainstem gliomas/Molecular pattern of adult brainstem gliomas/ Radiological pattern of adult brainstem gliomas based on standard and multimodal MRI/Metabolic pattern of adult brainstem gliomas based on 18F-DOPA PET CT at initial diagnosis and its change after treatment /Global survival/Quality of life questionnaire (EORTC QLQ-C30 with BN-20)/Tolerance to temozolomide/Volumetric velocity of the tumor growth during follow-up before treatment from the initial MRI until the last MRI before beginning of the treatment, established with sagittal cube FLAIR sequences/Volumetric velocity of the tumor growth during follow-up during treatment of chemotherapy, established with sagittal cube FLAIR sequences/Rate of objective response, stabilization and progression under treatment obtained by combining the RANO criteria and the scores obtained on 3 scales (ataxia measured by the Scale for the Assessment and Rating of Ataxia (SARA), diet measured by the Functional Oral Intake Scale (FOIS) and diplopia).A number of 60 patients should be enrolled. THe duration of the study is 4 years.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | First-line Chemotherapy With Temozolomide Alone for Non-enhancing Adult Brainstem Gliomas, With a Diffuse Subtype and Showing Clinical and/or Radiological Infiltrative Pattern of Progression |
| Actual Study Start Date : | July 26, 2019 |
| Estimated Primary Completion Date : | April 30, 2023 |
| Estimated Study Completion Date : | September 30, 2023 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Temozolomide
Chemotherapy by temozolomide
|
Drug: Temozolomide
Temozolomide at a monthly standard dose of 150-200 mg/m2/day at day 1 to day 5 for a duration of treatment of 12 months
|
Outcome Measures
Primary Outcome Measures :
- Objective response rate based on best response (Complete Response (CR) and Partial Response (PR)) to Temozolomide according to RANO criteria. [ Time Frame: Baseline, every month for up to 12 months from start of treatment ]A patient will be considered to be in an objective response to Temozolomide if the best response is a complete or partial response defined according to the RANO criteria.
Secondary Outcome Measures :
- Progression-free survival [ Time Frame: 15 months or later, up to 48 months ]
- Histological pattern of adult brainstem gliomas [ Time Frame: 15 months ]Description of the histological pattern of adult brainstem gliomas
- Molecular pattern of adult brainstem gliomas [ Time Frame: 15 months ]Description of the molecular pattern of adult brainstem gliomas
- Radiological pattern of adult brainstem gliomas based on standard and multimodal MRI [ Time Frame: 15 months ]Description of the radiological pattern of adult brainstem gliomas
- Metabolic pattern of adult brainstem gliomas based on 18F-DOPA PET CT at initial diagnosis and its change after treatment [ Time Frame: 15 months ]Description of the metabolic pattern of adult brainstem gliomas
- Volumetric velocity of the tumor growth before treatment start from the initial MRI until the last MRI before beginning of the treatment, established with sagittal cube FLAIR sequences [ Time Frame: Approximatively one month (before beginning of treatment) ]Description of the volumetric growth of adult brainstem gliomas before treatment
- Volumetric velocity of the tumor growth during treatment of chemotherapy, established with sagittal cube FLAIR sequences [ Time Frame: 12 months ]Description of the volumetric growth of adult brainstem gliomas before treatment
- Volumetric velocity of the tumor growth after treatment of chemotherapy, established with sagittal cube FLAIR sequences [ Time Frame: up to 48 months ]Description of the volumetric growth of adult brainstem gliomas after treatment
- Overall Survival [ Time Frame: 15 months or later, up to 48 months ]
- Total score of quality of life measured by European Organization for the Research and Treatment of Cancer Quality of Life questionnaires(EORTC QLQ-C30 and EORTC QLQ-BN20 together) during treatment [ Time Frame: Every 2 months up to 12 months ]
- 15-month life quality as measured by total score of European Organization for the Research and Treatment of Cancer Quality of Life questionnaires(EORTC QLQ-C30 and EORTC QLQ-BN20 together) [ Time Frame: At 15 months ]
- Objective response rate based on best response (CR and PR) to Temozolomide according to RANO criteria combined with total score obtained on three scales (ataxia measured by the SARA scale, diet/swallowing measured by the FOIS scale and diplopia). [ Time Frame: Baseline, every month for up to 12 months from start of treatment ]
A patient will be considered to be in an objective response to Temozolomide if the best response is a complete or partial response defined according to the RANO criteria and without degradation on the three scales or if the best response is stable according to RANO criteria with an improvement on one on the three scales without degradation of the two others.
An improvement is defined as an improvement of total score obtained on one of the three scales without degradation of the two others. Stabilization is defined as obtaining the same total score on all three scales. Degradation is defined as degradation of total score on at least one of the scales (even if the score obtained on another scale is improved)
- Tolerance to Temozolomide defined by the frequencies and grades of adverse events defined by the CTCAE v5.0 November 27, 2017 [ Time Frame: During chemotherapy and until 12 months ]
Eligibility Criteria
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 18 years of age or older
- Karnofsky's Index over 50
- Non-contrast lesion on MRI
-
Histologically proven low grade brainstem glioma with 2 exceptions:
- formal contraindication to surgery determined via discussion of the case with expert neurosurgeons during a national webmeeting (GLITRAD)
- negative brainstem biopsy These two exceptions may lead to case-by-case inclusion despite the lack of a histologically-proven diagnosis if clinical and radiological evidence support such a diagnosis and if a very detailed systemic check-up, standardized by the GLITRAD group (spinal MRI, whole body CT, PET, LP (if feasible), blood inflammatory and infectious counts, biopsy of the salivary glands, etc) is negative and allows us to state that this diagnosis is highly probable
- Clinical and/or radiological progression with an infiltrative but non-threatening pattern, warranting antitumoral treatment
- Absolute neutrophil count > 1.5 x 109/l,
- Platelets > 100 x 109/l
- Total bilirubin < 1.5 × ULN,
- AST and ALT< 3 x ULN
- Effective contraception
- Negative pregnancy test (serum beta-HCG) in females of reproductive age
- Written informed consent
- Affiliation to a social security scheme
Exclusion Criteria:
- Pilocytic astrocytoma
- Ependymoma
- Lack of a histologically proven diagnosis or an uncertain diagnosis regarding the tumoral nature and/or glial nature of the lesion after the GLITRAD webmeeting and a very detailed checkup looking for diagnostic pitfalls
- Contrast enhancement on MRI
- Clinico-radiological data favoring a more aggressive lesion, such as a high grade glioma, even in the case of a "low grade glioma" diagnosis after biopsy, suggesting histological under-grading
- Previous radiotherapy or chemotherapy for this lesion
- Contraindication to Temozolomide (Hypersensitivity to Temozolomide, dacarbazine or severe myelosuppression)
- Contraindication to IRM (pacemaker, intraocular metallic foreign bodies, intracranial metal clips, non-removable hearing aids, neurostimulation electrodes ...)
- Contraindication to IASOdopa® (hypersensitivity)
- Severe renal insufficiency
- Concomitant serious illness unbalanced that may interfere with follow-up
- History of malignancy within 5 years (excluding basal cell carcinoma or in situ carcinoma of the cervix)
- Pregnancy or breastfeeding
- Predictable difficulty with follow-up
- Patient under legal protection measures
Contacts and Locations
Contacts
| Contact: Florence LAIGLE-DONADEY, MD | 01 42 16 03 81 | florence.laigle-donadey@aphp.fr |
Locations
| France | |
| APHP - Groupe Hospitalier Pitié-Salpêtrière | Recruiting |
| Paris, France, 75013 | |
| Contact: Florence LAIGLE-DONADEY, MD 01 42 16 03 81 florence.laigle-donadey@aphp.fr | |
| Contact: Nabila ROUSSEAU nabila.rousseau@aphp.fr | |
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
| Principal Investigator: | Florence Florence, MD | APHP - Groupe Hospitalier Pitié-Salpêtrière |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | February 4, 2019 | ||||
| First Posted Date ICMJE | May 1, 2019 | ||||
| Last Update Posted Date | August 21, 2019 | ||||
| Actual Study Start Date ICMJE | July 26, 2019 | ||||
| Estimated Primary Completion Date | April 30, 2023 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Objective response rate based on best response (Complete Response (CR) and Partial Response (PR)) to Temozolomide according to RANO criteria. [ Time Frame: Baseline, every month for up to 12 months from start of treatment ] A patient will be considered to be in an objective response to Temozolomide if the best response is a complete or partial response defined according to the RANO criteria.
|
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
|
||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | First-line Chemotherapy With Temozolomide Alone for Non-enhancing Adult Brainstem Gliomas, With a Diffuse Subtype and Showing Clinical and/or Radiological Infiltrative Pattern of Progression | ||||
| Official Title ICMJE | First-line Chemotherapy With Temozolomide Alone for Non-enhancing Adult Brainstem Gliomas, With a Diffuse Subtype and Showing Clinical and/or Radiological Infiltrative Pattern of Progression | ||||
| Brief Summary | This phase 2 study is a prospective cohort study. Chemotherapy alone will be proposed to adult patients suffering from a "low grade" brainstem glioma subtype showing infiltrative, non-threatening clinico-radiological progression. Patients will receive temozolomide at a monthly standard dose of 150-200 mg/m2/j J1-J5, will be clinically evaluated every month and will undergo radiological evaluation every 2 months. The duration of treatment will be 12 months. Then, the patients will be followed-up until progression, with clinical evaluations and MRI performed every 2-3 months. At the time of recurrence, treatment with focal radiation therapy will be administered (54 Gy in classical fractions). | ||||
| Detailed Description | The goal of this study is to assess the impact (objective response) of first-line chemotherapy in infiltrative non-enhancing adult brainstem gliomas that are progressing in an infiltrative and non-threatening way. Upon progression, (radiotherapy) RT will be administered. Main inclusion criteria are:18 years of age or older/Karnofsky's Index over 50 /Non-enhancing lesion at MRI/Histologically proven infiltrating pattern of brainstem glioma except in case of formal contraindication to surgery determined via discussion of the case with expert neurosurgeons during a national webmeeting ((GLIome du TRonc de l'ADulte group (GLITRAD))/Clinical and/or radiological progression with an infiltrative but non-threatening pattern, warranting antitumoral treatment. The treatment delivered will be Temozolomide at a monthly standard dose of 150-200 mg/m2/day at day 1 to day 5 for a duration of treatment of 12 months. The study is a prospective single-arm phase II trial. Primary end point is objective response rate (radiographic and clinical response) to Temozolomide according to Response assessment in neuro-oncology criteria (RANO criteria). Secondary end points are histological pattern of adult brainstem gliomas/Molecular pattern of adult brainstem gliomas/ Radiological pattern of adult brainstem gliomas based on standard and multimodal MRI/Metabolic pattern of adult brainstem gliomas based on 18F-DOPA PET CT at initial diagnosis and its change after treatment /Global survival/Quality of life questionnaire (EORTC QLQ-C30 with BN-20)/Tolerance to temozolomide/Volumetric velocity of the tumor growth during follow-up before treatment from the initial MRI until the last MRI before beginning of the treatment, established with sagittal cube FLAIR sequences/Volumetric velocity of the tumor growth during follow-up during treatment of chemotherapy, established with sagittal cube FLAIR sequences/Rate of objective response, stabilization and progression under treatment obtained by combining the RANO criteria and the scores obtained on 3 scales (ataxia measured by the Scale for the Assessment and Rating of Ataxia (SARA), diet measured by the Functional Oral Intake Scale (FOIS) and diplopia).A number of 60 patients should be enrolled. THe duration of the study is 4 years. | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 2 | ||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||
| Condition ICMJE | Adult Brainstem Glioma | ||||
| Intervention ICMJE | Drug: Temozolomide
Temozolomide at a monthly standard dose of 150-200 mg/m2/day at day 1 to day 5 for a duration of treatment of 12 months
|
||||
| Study Arms ICMJE | Experimental: Temozolomide
Chemotherapy by temozolomide
Intervention: Drug: Temozolomide
|
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| Publications * | Not Provided | ||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Recruiting | ||||
| Estimated Enrollment ICMJE |
60 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Estimated Study Completion Date ICMJE | September 30, 2023 | ||||
| Estimated Primary Completion Date | April 30, 2023 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
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| Sex/Gender ICMJE |
|
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE |
|
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| Listed Location Countries ICMJE | France | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03932981 | ||||
| Other Study ID Numbers ICMJE | P160954J 2018-002654-79 ( EudraCT Number ) |
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| Has Data Monitoring Committee | No | ||||
| U.S. FDA-regulated Product |
|
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| IPD Sharing Statement ICMJE | Not Provided | ||||
| Responsible Party | Assistance Publique - Hôpitaux de Paris | ||||
| Study Sponsor ICMJE | Assistance Publique - Hôpitaux de Paris | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
|
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| PRS Account | Assistance Publique - Hôpitaux de Paris | ||||
| Verification Date | August 2019 | ||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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