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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01220271
First received: October 12, 2010
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Glioma
Drug: LY2157299
Drug: Radiation
Drug: Temozolomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Phase 1: Recommended dose for Phase 2 portion [ Time Frame: Baseline to phase 1 completion ] [ Designated as safety issue: Yes ]
  • Phase 2: Relationship of change in response biomarker to clinical benefit [ Time Frame: Baseline through discontinuation from any cause ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase 1: Pharmacokinetics - Concentration Maximum [ Time Frame: Baseline, prior to first dose of cycle 1 and 2 and on days 1, 3, 8, 14, 15 and 16 ] [ Designated as safety issue: No ]
  • Phase 1: Number of patients with a tumor response [ Time Frame: Baseline to Progressive Disease ] [ Designated as safety issue: No ]
  • Phase 2: Overall Survival at 12 Months [ Time Frame: Randomization to date of death from any cause at 12 months ] [ Designated as safety issue: Yes ]
  • Phase 2: Overall Survival [ Time Frame: Randomization to date of death from any cause ] [ Designated as safety issue: Yes ]
  • Phase 2: Progression Free Survival [ Time Frame: Randomization to measured progressive disease or death from any cause ] [ Designated as safety issue: Yes ]
  • Phase 2: Proportion of patients achieving an objective response (Response Rate) [ Time Frame: Randomization to measured progressive disease ] [ Designated as safety issue: Yes ]
  • Phase 2: Duration of tumor Response [ Time Frame: Time of response to measured progressive disease or death from any cause ] [ Designated as safety issue: Yes ]
  • Phase 2: Time to Treatment Failure [ Time Frame: Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause ] [ Designated as safety issue: Yes ]
  • Phase 1: Pharmacokinetics - Time to Concentration Maximum [ Time Frame: Baseline, prior to first dose of cycle 1 and 2 and on days 1, 3, 8, 14, 15 and 16 ] [ Designated as safety issue: No ]
  • Phase 1: Pharmacokinetics - Area under the Curve [ Time Frame: Days 12 to 14 in cycle 1 and in cycle 3 ] [ Designated as safety issue: No ]
  • Phase 2: Change from baseline in MD Anderson Symptom Inventory - Brain Tumor [ Time Frame: Baseline, 30 day post study day follow-up ] [ Designated as safety issue: No ]

Estimated Enrollment: 62
Study Start Date: April 2011
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01220271

Locations
United States, California
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, 92093
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, 94143
United States, Florida
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, United States, 33612
United States, Illinois
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, 60611
United States, Indiana
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, 46202
United States, North Carolina
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, 27710
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, 60596
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, Germany, 69120
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, 08035
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, 28041
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: NCT01220271     History of Changes
Other Study ID Numbers: 11585, H9H-MC-JBAI
Study First Received: October 12, 2010
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Spain: Spanish Agency of Medicines

Keywords provided by Eli Lilly and Company:
Glioma
Glioblastoma

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
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014