Clinical trial NCT01220271: A Study Combining LY2157299 With Temozolomide-based Radiochemotherapy in Patients With Newly Diagnosed Malignant Glioma
Official title: Phase 1b/2a Study Combining LY2157299 With Standard Temozolomide-based Radiochemotherapy in Patients With Newly Diagnosed Malignant Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glioma
Keywords: Glioma
Glioblastoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-10-13
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Recommended dose for Phase 2 portion
timeFrame: Baseline to phase 1 completion
measure: Phase 2: Relationship of change in response biomarker to clinical benefit
timeFrame: Baseline through discontinuation from any cause
Secondary outcomes:
measure: Phase 1: Pharmacokinetics - Concentration Maximum
timeFrame: Baseline, prior to first dose of cycle 1 and 2 and on days 1, 3, 8, 14, 15 and 16
measure: Phase 1: Number of patients with a tumor response
timeFrame: Baseline to Progressive Disease
measure: Phase 2: Overall Survival at 12 Months
timeFrame: Randomization to date of death from any cause at 12 months
measure: Phase 2: Overall Survival
timeFrame: Randomization to date of death from any cause
measure: Phase 2: Progression Free Survival
timeFrame: Randomization to measured progressive disease or death from any cause
measure: Phase 2: Proportion of patients achieving an objective response (Response Rate)
timeFrame: Randomization to measured progressive disease
measure: Phase 2: Duration of tumor Response
timeFrame: Time of response to measured progressive disease or death from any cause
measure: Phase 2: Time to Treatment Failure
timeFrame: Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause
measure: Phase 1: Pharmacokinetics - Time to Concentration Maximum
timeFrame: Baseline, prior to first dose of cycle 1 and 2 and on days 1, 3, 8, 14, 15 and 16
measure: Phase 1: Pharmacokinetics - Area under the Curve
timeFrame: Days 12 to 14 in cycle 1 and in cycle 3
measure: Phase 2: Change from baseline in MD Anderson Symptom Inventory - Brain Tumor
timeFrame: Baseline, 30 day post study day follow-up
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: 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.
state: California
city: San Francisco
country: United States
facility: 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.
state: California
city: Tampa
country: United States
facility: 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.
state: Florida
city: Chicago
country: United States
facility: 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.
state: Illinois
city: Indianapolis
country: United States
facility: 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.
state: Indiana
city: Durham
country: United States
facility: 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.
state: North Carolina
city: Frankfurt
country: Germany
facility: 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.
city: Heidelberg
country: Germany
facility: 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.
city: Barcelona
country: Spain
facility: 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.
city: Madrid
country: Spain
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Wick A, Desjardins A, Suarez C, Forsyth P, Gueorguieva I, Burkholder T, Cleverly AL, Estrem ST, Wang S, Lahn MM, Guba SC, Capper D, Rodon J. Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma. Invest New Drugs. 2020 Oct;38(5):1570-1579. doi: 10.1007/s10637-020-00910-9. Epub 2020 Mar 5.