A Study Combining LY2157299 With Temozolomide-based Radiochemotherapy in Patients With Newly Diagnosed Malignant Glioma

Glioma Clinical Trial

Official title:

Phase 1b/2a Study Combining LY2157299 With Standard Temozolomide-based Radiochemotherapy in Patients With Newly Diagnosed Malignant Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01220271
• Other study ID #: 11585
• Secondary ID: H9H-MC-JBAI
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 12, 2010
• Last updated: February 15, 2017
• Start date: April 2011
• Est. completion date: November 2016

Study information

• Verified date: February 2017
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to show proof of concept that by blocking the Transforming Growth Factor-beta signaling pathway in patients with Glioblastoma, there will be clinical benefit.

Phase 1b: To determine the safe and tolerable dose of LY2157299 in combination with radiochemotherapy with temozolomide for Phase 2 in patients with glioma eligible to receive radiochemotherapy with temozolomide (e.g. newly diagnosed malignant glioma World Health Organization Grade III and IV).

Phase 2a: To confirm the tolerability and evaluate the pharmacodynamic effect of LY2157299 in combination with standard radiochemotherapy in patients with newly diagnosed glioblastoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: November 2016
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with histologically proven, newly diagnosed and untreated intracranial glioblastoma including lower grade glioma which evolved into glioblastoma and who have not received any radiochemotherapy or who have World Health Organization Grade III malignant glioma (e.g., Anaplastic Astrocytomas, Anaplastic Oligoastrocytomas, Anaplastic Oligodendroglioma) (Phase 1b only) will be eligible for this protocol

• Biopsy or resection must have been performed no more than 6 weeks prior to treatment

• An Magnetic Resonance Imaging must be obtained within 72 hours after surgery, preferably within 48 hours

• Patient must not have had prior cranial radiation therapy

• Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors Patients who received Gliadel wafers at the time of original resection will be excluded

• Patients must plan to begin partial brain radiotherapy within 2-6 weeks after surgery. Regular fractionated radiotherapy with photons (in any planning mode and possibly image-guided or stereotactic if deemed necessary) is performed according to the discretion of the investigator

• Patients must be willing to forego other cytotoxic and noncytotoxic drug therapy against the tumor while being treated with LY2157299 and temozolomide

• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study

• Patients must have performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Patients must have adequate hematologic, hepatic and renal function

• Male and female patients with reproductive potential must use an approved contraceptive method,during and for 6 months after discontinuation of study treatment Women of childbearing potential must have a negative human chorionic gonadotropin pregnancy test documented within 14 days prior to treatment

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or not approved use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

• Have moderate or severe cardiac disease as defined by any of the following:

• 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 that are symptomatic and are not medically controlled

• Have major abnormalities documented by echocardiography with Doppler

• Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress

• Are unable to swallow tablets or capsules

• Are pregnant or breastfeeding

• Have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy

• Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and stopped all therapy for that disease for a minimum of 3 years are ineligible

• Have active infection that would interfere with the study objectives or influence the study compliance

• Stereotactic radiosurgery, such as Gamma-Knife treatment, and brachytherapy are not allowed in this study

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• LY2157299
Administered orally
• Radiation
Administered as approved
• Temozolomide
Administered orally

Locations

Country	Name	City	State
Germany	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	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
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
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.	Chicago	Illinois
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.	Durham	North Carolina
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.	Indianapolis	Indiana
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.	La Jolla	California
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.	San Francisco	California
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.	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Recommended dose for Phase 2 portion		Baseline to phase 1 completion
Primary	Phase 2: Relationship of change in response biomarker to clinical benefit		Baseline through discontinuation from any cause
Secondary	Phase 1: Pharmacokinetics - Concentration Maximum		Baseline, prior to first dose of cycle 1 and 2 and on days 1, 3, 8, 14, 15 and 16
Secondary	Phase 1: Number of patients with a tumor response		Baseline to Progressive Disease
Secondary	Phase 2: Overall Survival at 12 Months		Randomization to date of death from any cause at 12 months
Secondary	Phase 2: Overall Survival		Randomization to date of death from any cause
Secondary	Phase 2: Progression Free Survival		Randomization to measured progressive disease or death from any cause
Secondary	Phase 2: Proportion of patients achieving an objective response (Response Rate)		Randomization to measured progressive disease
Secondary	Phase 2: Duration of tumor Response		Time of response to measured progressive disease or death from any cause
Secondary	Phase 2: Time to Treatment Failure		Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause
Secondary	Phase 1: Pharmacokinetics - Time to Concentration Maximum		Baseline, prior to first dose of cycle 1 and 2 and on days 1, 3, 8, 14, 15 and 16
Secondary	Phase 1: Pharmacokinetics - Area under the Curve		Days 12 to 14 in cycle 1 and in cycle 3
Secondary	Phase 2: Change from baseline in MD Anderson Symptom Inventory - Brain Tumor		Baseline, 30 day post study day follow-up