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Adult GlioblastomaPhase 1/2GLYRadNCT02364206

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

A Phase 1/2 study testing LY2228820, Temozolomide and radiotherapy in people with Adult Glioblastoma, run by Centre Jean Perrin at 6 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Adult Glioblastoma
What is being tested?
LY2228820, Temozolomide and radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
6 sitesFrance
Study dates
8 Jun 2015to Aug 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

France6 sites

  • CHU Amiens Sud-Salouel

    Amiens

  • Institut Bergonié

    Bordeaux

  • Centre François Baclesse

    Caen

  • Centre Jean Perrin

    Clermont-Ferrand

  • Centre Georges François Leclerc

    Dijon

  • Centre Paul Strauss

    Strasbourg

Other trials in France

About this study

Official title: Phase I/II Study of LY2228820 With Radiotherapy Plus Concomitant TMZ in the Treatment of Newly Diagnosed Glioblastoma

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)

Being tested
LY2228820, Temozolomide, radiotherapy
Keywords
newly diagnosed glioblastoma, p38 MAPK inhibitor, temozolomide, radiotherapy
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LY2228820Drug

    Also called ralimetinib

  • TemozolomideDrug

    Also called TMZ

  • radiotherapyRadiation

Study groups in NCT02364206
Study groupRoleWhat they receive
LY2228820 + TMZ + RadiotherapyExperimentaladdition 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 .
Receives: Drug: LY2228820; Drug: Temozolomide; Radiation: radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. maximum tolerated dose (MTD) (phase I) of LY2228820 in combination with TMZ and radiotherapy during chemoradiotherapy period

    defined as the highest dose tested in which a dose limiting toxicity (DLT) is experienced by no more than 33% of patients during chemoradiotherapy period.

    Measured: from D1 Week 0 (first dose of LY2228820) to D63 Week 8.

  2. 6-month Progression Free Survival (PFS) rate (phase II) defined as the rate of patients who not presented a progression at 6 months from the first dose of LY2228820

    Measured: 6 months from the first dose of LY2228820

Secondary outcomes (9)

  1. Safety profile according to NCI Common Toxicity Criteria for Adverse Effect (CTCAE) criteria version 4.03.

    Measured: from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35)

  2. PFS

    disease progression assessed per Response Assessment in Neuro-Oncology (RANO) criteria

    Measured: from the first dose of LY2228820 to disease progression or death for any reason, up to 24 months

  3. Overall Survival

    Measured: from the first dose of LY2228820 to death, up to 24 months

  4. 12-month PFS rate defined as the rate of patients who not presented a progression at 12 months from the first dose of LY2228820

    Measured: 12 months from the first dose of LY2228820

  5. Objective response rate according to RANO criteria for patients with incomplete resection or only biopsy

    Measured: from the first dose of LY2228820 to treatment completion

  6. The neurologic status evaluated by clinical assessment and Mini-Mental State Examination (MMSE) and evaluation of corticosteroid dosage

    Measured: from baseline to progression, up to 24 months

  7. Pharmacokinetic of LY2228820 and TMZ (AUC0-12h)

    Measured: D7 Week 0, D28 Week 3, D35 Week 4

  8. MAPKAPK-2 activation

    in tumor and stromal cells and Peripheral Blood Mononucleated Cells (PBMCs)

    Measured: baseline (tumor) D1 D7 week 0, D28 Week 3, D35 Week 4 (PBMCs)

  9. Validated biomarker of glioblastoma (MGMT, IDH1 (isocitrate dehydrogenase 1), pTEN (phosphatase and tensin homolog), p53)

    on tumor

    Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2015 (estimated)
  2. Study start8 Jun 2015
  3. Primary completionAug 2019
  4. Study completionAug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02364206
Sponsor's protocol ID
2013-005442-11
Acronym
GLYRad
Status last verified
Aug 2019
First submitted
4 Feb 2015
Last updated
14 Aug 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LY2228820, Temozolomide and radiotherapy in people with Adult Glioblastoma, run by Centre Jean Perrin at 6 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

maximum tolerated dose (MTD) (phase I) of LY2228820 in combination with TMZ and radiotherapy during chemoradiotherapy period (time frame: from D1 Week 0 (first dose of LY2228820) to D63 Week 8.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02364206.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2019.

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