Study of LY2228820 With Radiotherapy Plus Concomitant TMZ in the Treatment of Newly Diagnosed Glioblastoma

NCT ID: NCT02364206

Last Updated: 2019-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-08
• Study Completion Date: 2019-08-31

Brief Summary

Glioblastomas are extremely resistant to treatment, including radiotherapy and/or chemotherapy. Mitogen-activated protein kinase (MAPK) cascades are key signaling pathways involved in the regulation of normal cell proliferation, survival and differentiation. Activation of p38 MAPK has been associated with a poor prognosis among patients with glioblastoma during the temozolomide (TMZ) era and represents a compensatory response by tumor cell to environmental stress such as radiation or chemotherapy.

LY2228820 is a potent and selective inhibitor of p38 MAPK, and reduces phosphorylation of its cellular target, MAPK-activated protein kinase 2 (MAPKAPK-2) . LY2228820 is a good candidate to target malignant glioma resistance to the gold standard treatment combining radiation and TMZ by acting on both tumor and stromal cells.

The primary objectives of this study were to determine the recommended dose of LY2228820 in combination with TMZ and radiotherapy during chemoradiotherapy period (phase I) and to estimate the 6-month progression free survival (PFS) rate of patients treated with LY2228820 when administered at the recommended dose in combination with radiotherapy and concomitant TMZ (phase II)

Conditions

Adult Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LY2228820 + TMZ + Radiotherapy

addition of LY2228820 to standard radiotherapy and concomitant treatment by temozolomide (TMZ).

LY2228820 will be administered orally for two 28 day cycles, from one week before the beginning of radiotherapy, and during standard chemoradiotherapy. Three dose levels of LY2228820 will be tested.

After a 4 week break after concomitant treatment, patient were then received up to 6 cycles of adjuvant TMZ according to the standard 5-day schedule every 28 days .

Group Type: EXPERIMENTAL

LY2228820

Intervention Type: DRUG

Temozolomide

Intervention Type: DRUG

radiotherapy

Intervention Type: RADIATION

Interventions

LY2228820

Intervention Type: DRUG

Temozolomide

Intervention Type: DRUG

radiotherapy

Intervention Type: RADIATION

Other Intervention Names

ralimetinib; TMZ

Eligibility Criteria

Inclusion Criteria

• Newly diagnosed and histologically confirmed glioblastoma
• Recursive partitioning analysis (RPA) class III or IV
• Age > or = 18 years and < 75 years of age
• Life expectancy > or = 6 months
• Patient must have at least 1 formalin fixed paraffin embedded tumor tissue block representative of glioblastoma available for pathology central review and biomarker exploration
• Adequate hematologic (absolute neutrophil count (ANC) > or = 1.5 x 109/L, platelet count > or = 100 x 109/L, hemoglobin > or = 10 g/dL ), renal (creatinine > or = 1.25 x ULN ), and hepatic function (total bilirubin < or = 1.5 x ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < or = 2.5 x ULN)
• Patients who were receiving corticosteroids had to receive a stable or decreasing dose for at least 14 days before enrollment
• Patients must be able to swallow and retain oral medication
• Women must have a negative serum pregnancy test less than 7 days prior to the first dose of study drug
• Both men and women of reproductive potential agree to use approved contraception during the study and for 6 months after discontinuation of study treatment.
• Willing and able to comply with the protocol as judged by the investigator
• Patients must provide written consent

Exclusion Criteria

• Any prior chemotherapy (including carmustine-containing wafers) or immunotherapy (including vaccine therapy )
• Any prior radiotherapy to the brain
• Any contraindication to temozolomide listed in the local label
• Have had, in the judgment of the investigator, a major bowel resection that would alter oral drug absorption
• Have a diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
• Have previously completed or withdrawn from this study or any other study investigating LY2228820
• Are receiving, in the judgment of the investigator, concurrent administration of immunosuppressive therapy
• Diarrhea of any cause CTCAE > or = grade 2
• Current or recent (within 30 days of enrollment) treatment with another investigational drug or participation in another investigational study
• History of other malignancy within 5 years prior enrollment except for basal cell carcinoma of the skin or carcinoma in situ of the cervix
• Pregnant or nursing (lactating) woman, or fertile women unwilling or unable to use effective means of contraception
• Psychiatric illness / social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance / pill diary

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, France

OTHER_GOV

Sponsor Role: collaborator

ARC Foundation for Cancer Research

OTHER

Sponsor Role: collaborator

Centre Jean Perrin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier DURANDO, Pr

Role: PRINCIPAL_INVESTIGATOR

Centre Jean Perrin

Locations

CHU Amiens Sud-Salouel

Amiens, , France

Institut Bergonié

Bordeaux, , France

Centre François Baclesse

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre Georges François Leclerc

Dijon, , France

Centre Paul Strauss

Strasbourg, , France

Countries

France

Other Identifiers

2013-005442-11

Identifier Type: -

Identifier Source: org_study_id