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

NCT01220271 | Completed Phase 1

• 2 other identifiers: 11585H9H-MC-JBAI
• Study Type: interventional
• Target: 75
• Locations: 3 countries
• Sites: 10

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.

Conditions

Glioma

Keywords

Glioma; Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Phase 1: Recommended dose for Phase 2 portion

  Baseline to phase 1 completion

• Phase 2: Relationship of change in response biomarker to clinical benefit

  Baseline through discontinuation from any cause

Secondary Outcomes (11)

• 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

• Phase 1: Number of patients with a tumor response

  Baseline to Progressive Disease

• Phase 2: Overall Survival at 12 Months

  Randomization to date of death from any cause at 12 months

• Phase 2: Overall Survival

  Randomization to date of death from any cause

• Phase 2: Progression Free Survival

  Randomization to measured progressive disease or death from any cause

Study Arms (4)

Phase 1: 160 mg LY2157299

EXPERIMENTAL

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; Drug: Radiation; Drug: Temozolomide

Phase 1: 300 mg LY2157299

EXPERIMENTAL

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; Drug: Radiation; Drug: Temozolomide

Phase 2: Established dose LY2157299

EXPERIMENTAL

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; Drug: Radiation; Drug: Temozolomide

Phase 2: no LY2157299 (control)

EXPERIMENTAL

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; Drug: Temozolomide

Interventions

LY2157299 DRUG

Administered orally

Phase 1: 160 mg LY2157299; Phase 1: 300 mg LY2157299; Phase 2: Established dose LY2157299

Radiation DRUG

Administered as approved

Phase 1: 160 mg LY2157299; Phase 1: 300 mg LY2157299; Phase 2: Established dose LY2157299; Phase 2: no LY2157299 (control)

Temozolomide DRUG

Administered orally

Phase 1: 160 mg LY2157299; Phase 1: 300 mg LY2157299; Phase 2: Established dose LY2157299; Phase 2: no LY2157299 (control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (10)

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, 92093, United States

Location

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, 94143, United States

Location

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, 33612, United States

Location

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, 60611, United States

Location

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, 46202, United States

Location

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, 27710, United States

Location

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, 60596, Germany

Location

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, 69120, Germany

Location

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, 08035, Spain

Location

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, 28041, Spain

Location

Related Publications (1)

• 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.

  PMID: 32140889 DERIVED

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

LY-2157299; Radiation; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Physical Phenomena; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2010
• First Posted: October 13, 2010
• Study Start: April 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: November 1, 2016
• Last Updated: February 16, 2017

Record last verified: 2017-02

Locations

US (6); DE (2); ES (2)