Diffuse Intrinsic Pontine Glioma MedDRA version: 17.0 Level: PT Classification code 10006143 Term: Brain stem glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: TARCEVA
Product Name: Erlotinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ERLOTINIB HYDROCHLORIDE
CAS Number: 183319-69-9
Concentration unit: mg milligram(s)
Concentrati
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Diagnosis of DIPG (clinical and radiological, or histological) -DIPG at diagnosis: no prior chemotherapy for the present cancer; no prior cerebral radiation therapy -NB : Metastatic disease allowed -Age > 6 months and 12 weeks after the start of study treatment -Karnofsky performance status scale or Lansky Play Scale > 50%. The PS should not take the neurologic deficit per se into account. NB: Children and young adults with a worse performance status due to glioma-related motor paresis can be included. -Absolute neutrophil count > 1.5 x 109/l, Platelets > 100 x 109/l -Total bilirubin 1,5 ULN, creatinine clearance must be > 70 ml/min/1,73 m² (EDTA radioisotope GFR or 24 hours urines collection) -Normal coagulation tests: prothrombin rate (prothrombin time = PT), TCA (PTT), fibrinogen -No current organ toxicity > grade 2 according to the NCI-CTCAE version 4.0 especially cardiovascular or renal disease (nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite adequate treatment). In case of known or possible cardiac disease, a cardiological advice will be required prior to the inclusion in the study if the patient may be allocated to the dasatinib cohort, i.e. presence of PDGFRA gain/amplification in the tumour. -Effective contraception for patients (male and female) of reproductive potential during their entire participation in the study and during 6 months after the end of treatment -Negative pregnancy test (serum beta-HCG) evaluated in the last week in females of reproductive potential Are the trial subjects under 18? yes Number of subjects for this age range: 150 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Massive intratumour bleeding -Any other concomitant anti-cancer treatment not foreseen by this protocol -Any other cancer during the last 5 years -Uncontrolled intercurrent illness or active infection -Any other co-morbid condition that in the investigator’s opinion would impair study participation -Unable for medical follow-up (geographic, social or mental reasons) -Patient not fulfilling one of the previous eligibility criteria. -Patient previously treated with irradiation on the brainstem for another neoplasm -Pregnant or breast feeding women -NB: A patient with known hypersensitivity for one the drug or its excipients could still participate to the study and receive one of the other drug(s)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to evaluate the relative efficacy in terms of two-year overall survival (OS) of erlotinib, everolimus and dasatinib in combination with radiation therapy, between randomised subsets of patients selected according to the biological abnormalities found in their tumour (two-by-two direct comparisons). ;Secondary Objective: Secondary objectives -To evaluate the safety profile of each of the three drugs when administered in combination with radiotherapy, and over the whole duration of treatment, as well as the feasibility of a protracted administration of these drugs; -To evaluate the efficacy in terms of overall survival (whole OS curves) and progression-free survival (PFS) of erlotinib, everolimus and dasatinib in combination with radiation therapy, comparatively between randomised subsets of patients, and also compared to historical controls; -To evaluate the whole strategy by estimating the overall and progression-free survival of the entire cohort (by pooling the different treatment arms) and comparing it to historical controls. ;Primary end point(s): Overall survival defined the time between study enrolment (or date of randomisation for the comparison of randomised groups) and death whatever the cause. The main analysis will be based on the 2-year OS estimate, but the whole survival curve will be estimated.;Timepoint(s) of evaluation of this end point: 2-year OS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Effcicacy endpoints Progression-free survival from the date of study enrolment (or date of randomisation for the comparison of randomised groups) to the date of unequivocal clinical or radiological progression, or death whatever the cause. Progression will be defined according to the RANO criteria. Toxicity The toxicity assessment will be conducted using the NCI-CTC V4 on the whole duration of treatment in all treatment arms, using a list of selected toxicity items for the most frequent expected toxicities and text fields for unexpected events and other less frequent toxicities. For each experimental treatment given in combination with radiotherapy, toxicity will be carefully monitored, based on the estimated proportion of patients experiencing one of the following adverse events, both in the first 8 weeks of treatment and on the whole treatment duration: -Grade 3 / 4 CTCAE non-haematological toxicity, excluding grade 3 nausea, vomiting, fever, and hepatic toxicity that is rapidly reversible (i.e. returns to < 2.5 x ULN within 2 weeks after study drug discontinuation), and excluding symptoms that are related to tumour progression or pseudo-progression (neurological deterioration, increased intracranial pressure); -Grade 4 CTCAE neutropenia lasting more than 7 days; -Grade 4 CTCAE thrombocytopenia persisting longer than 7 days or thrombocytopenia requiring transfusions for more than 7 days. Each of these adverse event must be communicated directly to the trial manager team and the sponsor coordinator. Feasibility -duration of treatment and description of the reasons for treatment discontinuation, -number of treatment temporary stops and dose-reductions and the description of the reasons for these treatment modifications, and -estimate of mean dose per week over the whole treatment duration. Translational study Response to therapy (PFS and OS) will be correlated to the biomarkers identified before the start and during the co | — |
Countries
Denmark, France, Netherlands, Spain, Sweden, United Kingdom
Contacts
Public ContactProject Manager
Gustave Roussy
Outcome results
None listed