A Dose-Escalation Study in Participants With Recurrent Malignant Glioma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01682187
First received: September 6, 2012
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Glioma
Drug: LY2157299
Drug: Lomustine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Dose-Escalation Study of LY2157299 Monotherapy and in Combination With Lomustine in Patients With Recurrent Malignant Glioma

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Recommended Dose for Phase 2 Studies [ Time Frame: Time of first dose to time of last dose (estimated up to 8 years) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Participants with Tumor Response [ Time Frame: Time of first dose to time of last dose (estimated up to 8 years) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: December 2005
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682187

Locations
United States, Maryland
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.
Baltimore, Maryland, United States
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.
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
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01682187     History of Changes
Other Study ID Numbers: 8660, H9H-MC-JBAH
Study First Received: September 6, 2012
Last Updated: April 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014