A Dose-Escalation Study in Participants With Recurrent Malignant Glioma

June 10, 2023 updated by: Eli Lilly and Company

Phase 1 Dose-Escalation Study of LY2157299 Monotherapy and in Combination With Lomustine in Patients With Recurrent Malignant Glioma

This is a study of oral LY2157299 as monotherapy and in combination with lomustine in participants with recurrent malignant glioma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain
        • 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.
      • Madrid, Spain
        • 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.
      • Sevilla, Spain
        • 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
    • Maryland
      • Baltimore, Maryland, United States
        • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have given written informed consent

  • Have histological or cytological evidence of relapsed malignant glioma (such as glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma) for which no treatment of higher priority exists

    • Available baseline tumor specimen is required prior to considering participant to be enrolled. The original diagnostic tumor tissue is sufficient for this inclusion criteria, but where possible, freshly obtained tumor biopsy material may be obtained
    • Measurable disease to allow assessment of tumor response based on radiographic assessment following Macdonald criteria and Response Evaluation Criteria In Solid Tumors (RECIST)
  • Have sufficient hepatic, renal, and hematological function
  • Have a performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy or other investigational therapy for at least 30 days prior to study enrollment and recovered from the acute effects of therapy
  • Able to swallow tablets and capsules
  • For females, reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method (including intrauterine or barrier devices) during and for 3 to 6 months after the study
  • Male participants must be willing to use contraception during and for 3 to 6 months after the study

Exclusion Criteria:

  • Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry

  • Have moderate or severe cardiac disease:

    • Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension
    • Have documented major electrocardiogram (ECG) abnormalities at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle branch blocks, ventricular hypertrophy, or recent myocardial infarction)
    • Have major abnormalities documented by echocardiography with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction (LVEF) <50%, evaluation based on the institutional lower limit of normal)
    • Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computerized tomography [CT] scan with contrast)
  • Have current acute or chronic leukemia
  • Women who are pregnant or lactating
  • Have received prior nitrosourea (including lomustine) therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LY2157299 (Part A)
Administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part A dose escalation will have starting dose of 40 mg/day and may increase up to 360 mg/day.
Drug: LY2157299
Administered orally
Experimental: LY2157299 + Lomustine (Part B)

LY21547299 will be administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part B dose expansion will have starting dose of 80 mg twice daily and may increase up to 150 mg twice daily.

Lomustine will be administered orally by capsule once on Day 7 of Cycle 1 after receiving LY2157299, and once after receiving LY2157299 on Day 21 of Cycles 2, 5, 8, 11, and every 4th cycle thereafter.
Drug: LY2157299
Administered orally
Drug: Lomustine
Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Recommended Dose for Phase 2 Studies
Time Frame: Time of first dose to time of last dose (estimated up to 8 years)
Time of first dose to time of last dose (estimated up to 8 years)

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of Participants with Tumor Response
Time Frame: Time of first dose to time of last dose (estimated up to 8 years)
Time of first dose to time of last dose (estimated up to 8 years)
Biologically Effective Dose Range
Time Frame: Baseline, Days 1, 12, 13 of Cycle 1, Days 1 and 12 of Cycle 2 of Part A - LY2157299 as monotherapy
Baseline, Days 1, 12, 13 of Cycle 1, Days 1 and 12 of Cycle 2 of Part A - LY2157299 as monotherapy
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC)
Time Frame: Part A Cycle 1: predose, up to 6 hours on Days 1, 3, 6, 12, 13, and 14; Part A Cycle 2: predose up to 6 hours on Days 1, 12, and 13. Part B Cycle 1: predose up to 6 hours on Days 1, 6, 7, 10, 12, 13, and 14
Part A Cycle 1: predose, up to 6 hours on Days 1, 3, 6, 12, 13, and 14; Part A Cycle 2: predose up to 6 hours on Days 1, 12, and 13. Part B Cycle 1: predose up to 6 hours on Days 1, 6, 7, 10, 12, 13, and 14
Pharmacokinetics (PK): Maximum Concentration (Cmax)
Time Frame: Part A Cycle 1: predose, up to 6 hours on Days 1, 3, 6, 12, 13, and 14; Part A Cycle 2: predose up to 6 hours on Days 1, 12, and 13. Part B Cycle 1: predose up to 6 hours on Days 1, 6, 7, 10, 12, 13, and 14
Part A Cycle 1: predose, up to 6 hours on Days 1, 3, 6, 12, 13, and 14; Part A Cycle 2: predose up to 6 hours on Days 1, 12, and 13. Part B Cycle 1: predose up to 6 hours on Days 1, 6, 7, 10, 12, 13, and 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2005

Primary Completion (Actual)

May 22, 2012

Study Completion (Estimated)

September 30, 2024

Study Registration Dates

First Submitted

September 6, 2012

First Submitted That Met QC Criteria

September 6, 2012

First Posted (Estimated)

September 10, 2012

Study Record Updates

Last Update Posted (Estimated)

June 13, 2023

Last Update Submitted That Met QC Criteria

June 10, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8660
  • H9H-MC-JBAH (Other Identifier: Eli Lilly and Company)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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