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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)

Primary Purpose

Adult Brainstem Glioma

Status

Unknown status

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Temozolomide

About this trial

This is an interventional treatment trial for Adult Brainstem Glioma focused on measuring Brainstem, Adult Glioma, Chemotherapy, Temozolomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

APHP - Groupe Hospitalier Pitié-SalpêtrièreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide

Arm Description

Chemotherapy by temozolomide

Outcomes

Primary Outcome Measures

Objective response rate based on best response (Complete Response (CR) and Partial Response (PR)) to Temozolomide according to RANO criteria.

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

Histological pattern of adult brainstem gliomas

Description of the histological pattern of adult brainstem gliomas

Molecular pattern of adult brainstem gliomas

Description of the molecular pattern of adult brainstem gliomas

Radiological pattern of adult brainstem gliomas based on standard and multimodal MRI

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

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

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

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

Description of the volumetric growth of adult brainstem gliomas after treatment

Overall Survival

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

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)

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).

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

Full Information

NCT ID

NCT03932981

First Posted

February 4, 2019

Last Updated

September 9, 2021

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT03932981

Brief 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

Acronym

TEMOTRAD01

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Unknown status

Study Start Date

July 26, 2019 (Actual)

Primary Completion Date

April 30, 2023 (Anticipated)

Study Completion Date

September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adult Brainstem Glioma

Keywords

Brainstem, Adult Glioma, Chemotherapy, Temozolomide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Temozolomide

Arm Type

Experimental

Arm Description

Chemotherapy by temozolomide

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Intervention Description

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

Primary Outcome Measure Information:

Title

Objective response rate based on best response (Complete Response (CR) and Partial Response (PR)) to Temozolomide according to RANO criteria.

Description

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.

Time Frame

Baseline, every month for up to 12 months from start of treatment

Secondary Outcome Measure Information:

Title

Progression-free survival

Time Frame

15 months or later, up to 48 months

Title

Histological pattern of adult brainstem gliomas

Description

Description of the histological pattern of adult brainstem gliomas

Time Frame

15 months

Title

Molecular pattern of adult brainstem gliomas

Description

Description of the molecular pattern of adult brainstem gliomas

Time Frame

15 months

Title

Radiological pattern of adult brainstem gliomas based on standard and multimodal MRI

Description

Description of the radiological pattern of adult brainstem gliomas

Time Frame

15 months

Title

Metabolic pattern of adult brainstem gliomas based on 18F-DOPA PET CT at initial diagnosis and its change after treatment

Description

Description of the metabolic pattern of adult brainstem gliomas

Time Frame

15 months

Title

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

Description

Description of the volumetric growth of adult brainstem gliomas before treatment

Time Frame

Approximatively one month (before beginning of treatment)

Title

Volumetric velocity of the tumor growth during treatment of chemotherapy, established with sagittal cube FLAIR sequences

Description

Description of the volumetric growth of adult brainstem gliomas before treatment

Time Frame

12 months

Title

Volumetric velocity of the tumor growth after treatment of chemotherapy, established with sagittal cube FLAIR sequences

Description

Description of the volumetric growth of adult brainstem gliomas after treatment

Time Frame

up to 48 months

Title

Overall Survival

Time Frame

15 months or later, up to 48 months

Title

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

Title

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

Title

Description

Time Frame

Baseline, every month for up to 12 months from start of treatment

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Florence LAIGLE-DONADEY, MD

Phone

01 42 16 03 81

florence.laigle-donadey@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Florence Florence, MD

Organizational Affiliation

APHP - Groupe Hospitalier Pitié-Salpêtrière

Official's Role

Principal Investigator

Facility Information:

Facility Name

APHP - Groupe Hospitalier Pitié-Salpêtrière

City

Paris

ZIP/Postal Code

75013

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Florence LAIGLE-DONADEY, MD

Phone

01 42 16 03 81

florence.laigle-donadey@aphp.fr

First Name & Middle Initial & Last Name & Degree

Nabila ROUSSEAU

nabila.rousseau@aphp.fr

12. IPD Sharing Statement

Learn more about this trial

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

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