NCT01582269CompletedPhase 2
A Phase 2 Study of LY2157299 Monohydrate Monotherapy or LY2157299 Monohydrate Plus Lomustine Therapy Compared to Lomustine Monotherapy in Patients With Recurrent Glioblastoma
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 158
- Locations
- 1
- Primary Endpoint
- Overall Survival (OS)
Study Overview
Brief Summary
The purpose of the study is to see whether treatment with LY2157299 on its own, LY2157299 plus lomustine therapy or lomustine plus placebo can help participants with brain cancer
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histological confirmed diagnosis of relapsed intracranial GB
- •Progressive Disease (PD) following standard chemoradiation
- •Prior surgical resection allowed
- •Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1
- •Adequate hematologic, hepatic and renal function
- •Discontinued all prior cancer treatments for cancer & recovered from the acute effects of therapy
- •Tumor specimen must be available for a central pathology review and prognostic and predictive biomarker evaluation
Exclusion Criteria
- •Moderate or severe heart disease based on New York Heart Association (NYHA) criteria
- •Prior nitrosurea therapy (including lomustine or Gliadel)
- •Prior bevacizumab as 1st line treatment for GB (if treatment was concluded 12 months prior to enrollment, the patient may be eligible to participate in the trial)
- •Current acute or chronic myelogenous leukemia
- •Second primary malignancy that may affect the interpretation of results
- •Serious concomitant systemic disorder
Arms & Interventions
Arm A: Galunisertib
Experimental
- Participants received Galunisertib 300 milligrams (mg) orally twice daily (BID) for 14 days, followed by 14 days of rest in a 28-day cycle.
- Treatment continued until disease progression, death, or discontinuation criteria were met.
Intervention: Galunisertib (Drug)
Arm B: Galunisertib + Lomustine
Experimental
- Participants received Galunisertib 300 mg orally BID for 14 days, followed by 14 days of rest in a 28-day cycle.
- Participants received a first dose of Lomustine at 100 milligrams per square meter (mg/m²) administered orally. Thereafter, starting with the second dose, Lomustine was administered orally once every 6 weeks at 100-130 mg/m², at the discretion of the investigator.
- Treatment continued until disease progression, death, or discontinuation criteria were met.
Intervention: Galunisertib (Drug)
Arm B: Galunisertib + Lomustine
Experimental
- Participants received Galunisertib 300 mg orally BID for 14 days, followed by 14 days of rest in a 28-day cycle.
- Participants received a first dose of Lomustine at 100 milligrams per square meter (mg/m²) administered orally. Thereafter, starting with the second dose, Lomustine was administered orally once every 6 weeks at 100-130 mg/m², at the discretion of the investigator.
- Treatment continued until disease progression, death, or discontinuation criteria were met.
Intervention: Lomustine (Drug)
Arm C: Lomustine + Placebo
Active Comparator
- Participants received a first dose of Lomustine at 100 mg/m² administered orally. Thereafter, starting with the second dose, Lomustine was administered orally once every 6 weeks at 100-130 mg/m², at the discretion of the investigator.
- Participants received Galunisertib-matched Placebo orally BID for 14 days, followed by 14 days of rest in a 28-day cycle.
- Treatment continued until disease progression, death, or discontinuation criteria were met.
Intervention: Lomustine (Drug)
Arm C: Lomustine + Placebo
Active Comparator
- Participants received a first dose of Lomustine at 100 mg/m² administered orally. Thereafter, starting with the second dose, Lomustine was administered orally once every 6 weeks at 100-130 mg/m², at the discretion of the investigator.
- Participants received Galunisertib-matched Placebo orally BID for 14 days, followed by 14 days of rest in a 28-day cycle.
- Treatment continued until disease progression, death, or discontinuation criteria were met.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Randomization to Date of Death from Any Cause (Up To 20.5 Months)
OS is defined as the time from the date of randomization until death from any cause. For participants not known to have died by the data-inclusion cutoff date, OS is censored at the last date they were known to be alive.
Secondary Outcomes
- Progression Free Survival (PFS)(Randomization to Objective Progression or Death Due to Any Cause (Up To 19 Months))
- Percentage of Participants With Tumour Response(Randomization until measured progressive disease (Up To 19 Months))
- Population Pharmacokinetics (PopPK): Absorption Rate Constant of Galunisertib (Arm A: Galunisertib and Arm B: Galunisertib + Lomustine)(Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours (h), 3.5-5 h, and 48 h post-dose; Day 14: Predose, 0.5-2 h, 3.5-5 h, 24 h, and 48 h post last dose)
- Population Pharmacokinetics (PopPK): Mean Steady State Apparent Volume of Distribution (Vss) of Galunisertib (Arm A: Galunisertib and Arm B: Galunisertib + Lomustine)(Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours (h), 3.5-5 h, and 48 h post-dose; Day 14: Predose, 0.5-2 h, 3.5-5 h, 24 h, and 48 h post last dose)
- Population Pharmacokinetics (PopPK): Mean Population Clearance of Galunisertib (Arm A: Galunisertib and Arm B: Galunisertib + Lomustine)(Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours (h), 3.5-5 h, and 48 h post-dose; Day 14: Predose, 0.5-2 h, 3.5-5 h, 24 h, and 48 h post last dose)
- Change From Baseline in Neurocognitive Function Using Hopkins Verbal Learning Test-Revised (HVLT-R)(Baseline, Month 20)
- Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom and Interference Severity Scores: (Brain Tumor Symptoms, Core Symptoms, Interference Symptoms)(Baseline, Month 21)
Investigators
Study Sites (1)
Loading locations...
Similar Trials
Active, not recruiting
Not Applicable
A study in recurrent glioblastomaglioblastomaMedDRA version: 14.1Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2011-004418-40-ITELI LILLY180
Active, not recruiting
Not Applicable
A Study in Recurrent GlioblastomaGlioblastomaEUCTR2011-004418-40-NLEli Lilly and Company180
Active, not recruiting
Phase 1
A Study in Recurrent GlioblastomaGlioblastomaEUCTR2011-004418-40-PLEli Lilly and Company180
Completed
Phase 2
A Phase 2 Study of LY2157299 Monohydrate Monotherapy or LY2157299 Monohydrate plus Lomustine Therapy compared to Lomustine Monotherapy in Patients with Recurrent GlioblastomaNL-OMON37449Eli Lilly10
Active, not recruiting
Phase 1
A Study in Recurrent GlioblastomaGlioblastomaEUCTR2011-004418-40-DEEli Lilly and Company180