A Study in Recurrent Glioblastoma (GB)

A Phase 2 Study of LY2157299 Monohydrate Monotherapy or LY2157299 Monohydrate Plus Lomustine Therapy Compared to Lomustine Monotherapy in Patients With Recurrent Glioblastoma

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 Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Placebo; Drug: Galunisertib; Drug: Lomustine

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Parkville, Victoria, Australia, 3050
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Belgium
  • Edegem, Belgium, 2650
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Ghent, Belgium, 9000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Liège, Belgium, 4000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• France
  • Bobigny, France, 93009
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Lyon, France, 69394
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Marseille, France, 13385
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Nancy, France, 54035
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Paris, France, 75651
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Germany
  • Bonn, Germany, 53105
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Frankfurt, Germany, 60596
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Hamburg, Germany, 20246
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Heidelberg, Germany, 69120
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Italy
  • Bologna, Italy, 40139
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Terni, Italy, 05100
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Udine, Italy, 33100
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Rotterdam, Netherlands, 3075 EA
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Poland
  • Lodz, Poland, 93-509
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Spain
  • Barcelona, Spain, 08035
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • California
    • La Jolla, California, United States, 92093
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • San Francisco, California, United States, 94143
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Texas
    • Dallas, Texas, United States, 75246
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Galunisertib; 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.	Drug: Galunisertib; Administered orally; Other Names: LY2157299 monohydrate
Experimental: Arm B: Galunisertib + Lomustine; 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.	Drug: Galunisertib; Administered orally; Other Names: LY2157299 monohydrate; Drug: Lomustine; Administered orally
Active Comparator: Arm C: Lomustine + Placebo; 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.	Drug: Placebo; Administered orally; Other Names: Galunisertib-matched Placebo; Drug: Lomustine; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	Randomization to Date of Death from Any Cause (Up To 20.5 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time from randomization to the date of the first observation of objective disease progression or death from any cause, whichever occurred first. Participants known to be alive and without disease progression were censored at the date of their last objective progression-free disease assessment prior to the initiation of any subsequent systemic anticancer therapy.	Randomization to Objective Progression or Death Due to Any Cause (Up To 19 Months)
Percentage of Participants With Tumour Response	Tumour response was assessed using Response Assessment in Neuro-Oncology (RANO) criteria. Responses included Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). CR required disappearance of all enhancing lesions, no new lesions, stable or improved non-enhancing lesions, and no corticosteroid use. PR was defined as ≥50% reduction in enhancing lesion size, no new lesions, stable or improved non-enhancing lesions, and stable or reduced corticosteroid use. SD indicated no significant change in lesion size or clinical status. PD was defined as ≥25% increase in lesion size, new lesions, or clinical deterioration. Percentage of participants with tumor response is defined as the percentage of participants who achieved these tumor responses based on RANO criteria.Participants whose tumor response could not be assessed due to inadequate imaging data were categorized as 'Unknown'.	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)	The absorption rate constant (Ka) of Galunisertib was estimated using PopPK modeling based on plasma concentration-time data collected during Cycle 1. A two-compartment model with first-order absorption was applied using nonlinear mixed-effects modeling. Samples were collected at the following time points: Cycle 1 Day 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. Individual participant Ka values were derived from model-estimated parameters using all available PK timepoints.The reported outcome is the mean of these individual Ka estimates across both treatment arms (Arm A: Galunisertib; 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)	The Vss at steady state of Galunisertib was estimated using PopPK modeling based on plasma concentration-time data collected during Cycle 1.A two-compartment model was applied using nonlinear mixed-effects modeling. Samples were collected at the following time points: Cycle 1 Day 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. Individual participant Vss values were derived from model-estimated parameters using all available PK timepoints. The reported outcome is the mean of individual Vss estimates across both treatment arms (Arm A: Galunisertib; 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)	The apparent clearance (CL/F) of Galunisertib was estimated using PopPK modeling based on plasma concentration-time data collected during Cycle 1. A two-compartment model was applied using nonlinear mixed-effects modeling. Samples were collected at the following time points: Cycle 1 Day 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. Individual participant CL/F values were derived from model-estimated parameters using all available PK timepoints. The reported outcome is the mean of these individual CL/F estimates across both treatment arms (Arm A: Galunisertib; 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)	The Hopkins Verbal Learning Test-Revised comprises: 3 Learning Trials: Participants were presented with a list of 12 words (from 3 semantic categories) and were asked to recall them to test verbal learning and memory.; Delayed Recall Trial: Conducted 20-25 minutes after the 3rd learning trial to test memory retention.; Delayed Recognition Trial: Participants identified previously presented words from a list that included 12 distractors to test recognition discrimination. Scoring Components: Total Recall Score (0-36): Sum of correctly recalled words across the 3 learning trials.; Delayed Recall Score (0-12): Number of correct words recalled after the delay.; Recognition Discrimination Index Score (+12 to -12): Calculated as the number of true positives (correctly identified words) minus false positives (incorrectly identified words, i.e., distractors). For each of the 3 reported scores, higher scores = better neurocognitive performance; lower scores = decline.	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)	The MDASI-BT assesses the severity of multiple brain tumor-related symptoms and the impact of these symptoms on daily functioning in the last 24 hours. It includes: 13 core symptoms measuring severity of pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, memory problems, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness/tingling, rated 0-10, where 0 = "not present" and 10 = "as bad as you can imagine."; 9 brain tumor-specific symptoms assess severity of difficulty speaking, weakness, seizures, difficulty understanding, vision changes, appearance changes, bowel pattern changes, concentration problems, and irritability, rated 0-10, where 0 = "not present" and 10 = "as bad as you can imagine."; 6 interference items assess impact on general activity, mood, work, relations, walking, and enjoyment of life, rated 0-10, where 0 = "did not interfere" and 10 = "interfered completely."	Baseline, Month 21

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Smith CL, Thomas Z, Enas N, Thorn K, Lahn M, Benhadji K, Cleverly A. Leveraging historical data into oncology development programs: Two case studies of phase 2 Bayesian augmented control trial designs. Pharm Stat. 2020 May;19(3):276-290. doi: 10.1002/pst.1990. Epub 2020 Jan 5.
• Brandes AA, Carpentier AF, Kesari S, Sepulveda-Sanchez JM, Wheeler HR, Chinot O, Cher L, Steinbach JP, Capper D, Specenier P, Rodon J, Cleverly A, Smith C, Gueorguieva I, Miles C, Guba SC, Desaiah D, Lahn MM, Wick W. A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma. Neuro Oncol. 2016 Aug;18(8):1146-56. doi: 10.1093/neuonc/now009. Epub 2016 Feb 21.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2012
• Primary Completion (Actual): July 26, 2014
• Study Completion (Actual): October 10, 2024

Study Registration Dates

• First Submitted: April 19, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimated): April 20, 2012

Study Record Updates

• Last Update Posted (Estimated): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 12, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Organic Chemicals; Amides; Nitrosourea Compounds; Urea; Nitroso Compounds; Lomustine; LY-2157299
• Other Study ID Numbers: 13849; H9H-MC-JBAL (Other Identifier: Eli Lilly and Company); 2011-004418-40 (EudraCT Number)