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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01220271
Collaborator
(none)
75
Enrollment
10
Locations
4
Arms
67.1
Duration (Months)
7.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
75 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b/2a Study Combining LY2157299 With Standard Temozolomide-based Radiochemotherapy in Patients With Newly Diagnosed Malignant Glioma
Study Start Date :
Apr 1, 2011
Actual Primary Completion Date :
Aug 1, 2015
Actual Study Completion Date :
Nov 1, 2016

Arms and Interventions

ArmIntervention/Treatment
Experimental: Phase 1: 160 mg LY2157299

During Radiation therapy: Radiation:Approximate 1.8 - 2.0 Gy x 30 fractions. Approximate total dose = 60.0 Gy taken 5 days per week for 6 weeks. LY2157299: 80 mg taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Temozolomide: 75 mg/m2 taken daily for 6 weeks. After Radiation Therapy: LY2157299: 80 mg taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Taken for a 6 cycles. Temozolomide: 150 mg/m2 and then 200 mg/m2 daily during the off time of LY2157299. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles.

Drug: LY2157299
Administered orally

Drug: Radiation
Administered as approved

Drug: Temozolomide
Administered orally

Experimental: Phase 1: 300 mg LY2157299

During Radiation therapy: Radiation:Approximate 1.8 - 2.0 Gy x 30 fractions. Approximate total dose = 60.0 Gy taken 5 days per week for 6 weeks. LY2157299: 150 mg taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Temozolomide: 75 mg/m2 taken daily for 6 weeks. After Radiation Therapy: LY2157299: 150 mg taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Taken for a 6 cycles. Temozolomide: 150 mg/m2 and then 200 mg/m2 daily during the off time of LY2157299. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles.

Drug: LY2157299
Administered orally

Drug: Radiation
Administered as approved

Drug: Temozolomide
Administered orally

Experimental: Phase 2: Established dose LY2157299

During Radiation therapy: Radiation:Approximate 1.8 - 2.0 Gy x 30 fractions. Approximate total dose = 60.0 Gy taken 5 days per week for 6 weeks. LY2157299: Phase 1 established dose taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Temozolomide: 75 mg/m2 taken daily for 6 weeks. After Radiation Therapy: LY2157299: Phase 1 established dose taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Taken for a 6 cycles. Temozolomide: 150 mg/m2 and then 200 mg/m2 daily during the off time of LY2157299. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles.

Drug: LY2157299
Administered orally

Drug: Radiation
Administered as approved

Drug: Temozolomide
Administered orally

Experimental: Phase 2: no LY2157299 (control)

During Radiation therapy: Radiation:Approximate 1.8 - 2.0 Gy x 30 fractions. Approximate total dose = 60.0 Gy taken 5 days per week for 6 weeks. Temozolomide: 75 mg/m2 taken daily for 6 weeks. After Radiation Therapy: Temozolomide: 150 mg/m2 and then 200 mg/m2 daily during the off time of LY2157299. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles.

Drug: Radiation
Administered as approved

Drug: Temozolomide
Administered orally

Outcome Measures

Primary Outcome Measures

  1. Phase 1: Recommended dose for Phase 2 portion [Baseline to phase 1 completion]

  2. Phase 2: Relationship of change in response biomarker to clinical benefit [Baseline through discontinuation from any cause]

Secondary Outcome Measures

  1. 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]

  2. Phase 1: Number of patients with a tumor response [Baseline to Progressive Disease]

  3. Phase 2: Overall Survival at 12 Months [Randomization to date of death from any cause at 12 months]

  4. Phase 2: Overall Survival [Randomization to date of death from any cause]

  5. Phase 2: Progression Free Survival [Randomization to measured progressive disease or death from any cause]

  6. Phase 2: Proportion of patients achieving an objective response (Response Rate) [Randomization to measured progressive disease]

  7. Phase 2: Duration of tumor Response [Time of response to measured progressive disease or death from any cause]

  8. 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]

  9. 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]

  10. Phase 1: Pharmacokinetics - Area under the Curve [Days 12 to 14 in cycle 1 and in cycle 3]

  11. Phase 2: Change from baseline in MD Anderson Symptom Inventory - Brain Tumor [Baseline, 30 day post study day follow-up]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1For 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 JollaCaliforniaUnited States92093
2For 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 FranciscoCaliforniaUnited States94143
3For 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.TampaFloridaUnited States33612
4For 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.ChicagoIllinoisUnited States60611
5For 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.IndianapolisIndianaUnited States46202
6For 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.DurhamNorth CarolinaUnited States27710
7For 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.FrankfurtGermany60596
8For 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.HeidelbergGermany69120
9For 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.BarcelonaSpain08035
10For 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.MadridSpain28041

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01220271
Other Study ID Numbers:
  • 11585
  • H9H-MC-JBAI
First Posted:
Oct 13, 2010
Last Update Posted:
Feb 16, 2017
Last Verified:
Feb 1, 2017
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 16, 2017