A Study in Recurrent Glioblastoma (GB)

Study Description

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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

Condition or disease	Intervention/treatment	Phase
Glioblastoma	Drug: LY2157299 monohydrate; Drug: Lomustine; Drug: Placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	180 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	A Phase 2 Study of LY2157299 Monohydrate Monotherapy or LY2157299 Monohydrate Plus Lomustine Therapy Compared to Lomustine Monotherapy in Patients With Recurrent Glioblastoma
Study Start Date :	April 2012
Actual Primary Completion Date :	July 2014
Estimated Study Completion Date :	December 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: LY2157299 monohydrate plus lomustine; 300 mg/day LY2157299, given orally for 14 days, followed by 14 days of rest, equaling a 28-day cycle. First lomustine dose will be given as 100 mg/m2 on day 7 cycle 1. Remaining doses are based on the investigator's discretion and will be given orally once every 6 weeks in capsules to equal 100 to 130 mg/m2.	Drug: LY2157299 monohydrate; Orally administered as tablets; Other Name: LY2157299 Drug: Lomustine; Orally administered as capsules
Experimental: LY2157299 monohydrate; 300 mg/day LY2157299, given orally for 14 days, followed by 14 days of rest, equaling a 28-day cycle (unblinded)	Drug: LY2157299 monohydrate; Orally administered as tablets; Other Name: LY2157299
Active Comparator: lomustine plus placebo; First lomustine dose will be given as 100 mg/m2 on day 7 cycle 1. Remaining doses are based on the investigator's discretion and will be given orally once every 6 weeks in capsules to equal 100 to 130 mg/m2. LY2157299 monohydrate-matched placebo, given orally as tablets for 14 days, followed by 14 days of rest, equaling a 28-day cycle.	Drug: Lomustine; Orally administered as capsules Drug: Placebo; Orally administered as tablets; Other Name: LY2157299 monohydrate-matched placebo

Outcome Measures

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Primary Outcome Measures :

1. Overall survival [ Time Frame: Date of randomization to date of death from any cause estimated up to 2 years ]

Secondary Outcome Measures :

1. Population Pharmacokinetics (PK): median population clearance [ Time Frame: Cycle 1, Day 1, 3, 14, 15 and 16 ]
2. Progression free survival (PFS) [ Time Frame: Randomization to the date of objective progression or death from any cause estimated up to 2 years ]
3. Percentage of Participants with Tumor Response [ Time Frame: Every 2 cycles to disease progression or participant starts a new anticancer therapy estimated up to 2 years ]
4. Change from baseline in neurocognitive function [ Time Frame: Baseline, cycle 1, cycle 2 then every 2 cycles to 30 day post discontinuation follow up estimated up to 2 years ]
5. Population Pharmacokinetics (PK): absorption [ Time Frame: Cycle 1, Day 1, 3, 14, 15 and 16 ]
6. Population Pharmacokinetics (PK): volume of distribution [ Time Frame: Cycle 1, Day 1, 3, 14, 15 and 16 ]
7. Change from baseline in MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) score [ Time Frame: Baseline, cycle 1, cycle 2 then every 2 cycles to 30 day post discontinuation follow up estimated up to 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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  Show 27 Study Locations

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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT01582269 History of Changes
Other Study ID Numbers:	13849; H9H-MC-JBAL ( Other Identifier: Eli Lilly and Company )
First Posted:	April 20, 2012
Last Update Posted:	November 20, 2017
Last Verified:	November 2017

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; 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; Antineoplastic Agents