Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Lomustine

Antineoplastic Agents, Alkylating

Alkylating Agents

Administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part A dose escalation will have starting dose of 40 mg/day and may increase up to 360 mg/day.

LY21547299 will be administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part B dose expansion will have starting dose of 80 mg twice daily and may increase up to 150 mg twice daily.

Lomustine will be administered orally by capsule once on Day 7 of Cycle 1 after receiving LY2157299, and once after receiving LY2157299 on Day 21 of Cycles 2, 5, 8, 11, and every 4th cycle thereafter.

LY2157299

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)

This is a study of oral LY2157299 as monotherapy and in combination with lomustine in participants with recurrent malignant glioma.

A Dose-Escalation Study in Participants With Recurrent Malignant Glioma

Phase 1 Dose-Escalation Study of LY2157299 Monotherapy and in Combination With Lomustine in Patients With Recurrent Malignant Glioma

Eli Lilly and Company

Glioblastoma

Temozolomide

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.

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.

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.

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.

Radiation

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.

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

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

Neoplasm Metastasis

Neoplastic Processes

80 up to 150 milligrams of LY2157299 administered orally, twice daily for 14 days, followed by 14 days with no study drug (2 weeks on/2 weeks off schedule) for at least two 28 day cycles. Participants receiving clinical benefit may continue receiving treatment until discontinuation criterion is met.

Call 1-877-CTLILLY (1-877-285-4559 ) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST)

The main purpose of this study is to evaluate the safety and side effects of LY2157299 in Japanese participants with advanced cancer or cancer that has spread to other parts of the body.

Study of LY2157299 in Japanese Participants With Cancer

Phase 1 Dose-Escalation Study of LY2157299 Monotherapy in Patients With Solid Tumors

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

LY2157299 will be administered orally twice daily for 14 days, followed by 14 days with no study drug per 28-day cycle. Sorafenib will be administered orally twice daily for 28 days, in each cycle.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST)

The main purpose of this study is to evaluate safety and tolerability of LY2157299 when combined with sorafenib in Japanese hepatocellular carcinoma (HCC) participants.

A Study of LY2157299 in Participants With Unresectable Hepatocellular Cancer (HCC)

A Phase 1b Study of LY2157299 in Combination With Sorafenib in Patients With Unresectable Hepatocellular Carcinoma

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Rectal Diseases

Camurati-Engelmann Disease

Capecitabine

Fluorouracil

Immunomodulating Agents

Mitogens

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Patients will receive a 14 day course of LY2157299. On day 15 patients will begin chemoradiation treatment with Capecitabine or Fluorouracil. On day 29, patients will undergo another fourteen day course of LY2157299 concurrent with their ongoing chemoradiation treatment. Six to ten weeks after completing their neoadjuvant therapy, patient will undergo a tumor specific mesorectal excision as per standard of care.

Small molecule inhibitor of transforming growth factor-beta signaling pathway

Tumor specific mesorectal excision

Kristina Young, MD, PhD

Todd Crocenzi, MD

The purpose of this study is to see how effective and safe LY2157299, in combination with chemotherapy and radiation therapy, might be in treating rectal cancer. Also as part of this study, research will be done on tumor samples to see if it is possible to predict if patients will respond to treatment, and blood samples to look at the immune system response to study treatment.

About 50 people will take part in this study. The study treatment will be given over an 8 week period and the investigators will continue to collect your health information for up to 5 years, as part of this study

This is a prospective Phase II study to test the efficacy of LY2157299 in combination with neoadjuvant chemoradiation in patients with rectal adenocarcinoma. This study will test the hypothesis that LY2157299 will improve effector T cell tumor infiltration and activity resulting in improved pathologic response rates. The investigators propose that this improved immune response will result in improved disease-free and overall survival.

The objectives are:

1. Determine the rate of pathologic complete response in patients with locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation and the investigational agent LY2157299
2. Correlate immunoscore changes prior to therapy, during therapy, and at surgical resection with pathologic response and MRI parameters
3. Immune monitoring to evaluate potential biomarkers of treatment success.

Eligible patients will have histologically confirmed rectal adenocarcinoma, AJCC Stage IIA IIIC or AJCC Stage IV appropriate for consideration of primary rectal tumor resection. Patients will undergo a forceps biopsy of the rectal mass as part of the diagnostic workup as well as undergo staging evaluation including an MRI with additional study sequences. Enrolled patients will receive a 14 day course of LY2157299 followed by a repeat biopsy and MRI with study sequences. In this trial the investigators plan to use the maximum tolerated dose of LY2157299 established in human clinical trials, 300mg delivered as 150mg P.O. BID. On day 15 patients will begin chemoradiation with either 5-FU (fluorouracil ) or capecitabine (Xeloda®). On day 29, patients will undergo another fourteen day course of LY2157299 concurrent with their ongoing chemoradiation.

Patients will undergo 50.4 to 54Gy of radiation in 1.8Gy daily fractions delivered Monday through Friday for a total of 28-30 fractions. The acceptable duration of chemoradiation, including treatment breaks or delays, is up to 8 weeks total. Six to ten weeks after completing their neoadjuvant therapy, patient will undergo a tumor specific mesorectal excision as per standard of care with evaluation of pathologic response rate. Patients will be followed for disease-free survival, progression free survival, local recurrence, and overall survival. A three patient safety lead-in will be performed, where a six week safety period following completion of radiation will be completed prior to enrolling subsequent patients.

ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer

Phase II Study of TGFβ Type I Receptor Inhibitor LY2157299 With Neoadjuvant Chemoradiation in Patients With Locally Advanced Rectal Adenocarcinoma

Complete response is defined as no viable tumor cells identified.

For the immunoscore, a value of 0 or 1 is assigned to each cell population of interest with 0 corresponding to a poor immune infiltrate and 1 corresponding to a favorable immune infiltrate as determined by immunohistochemistry.

Investigators will test a minimum of three MRI parameters including but not limited to ADC and f_p from the IVIM sequence, and Ktrans from the DCE sequence.

The immunologic monitoring parameters will be combined to arrive at an aggregated measure of "pro-tumor immune environment" or "anti-tumor immune environment" using cell counts derived from flow cytometry of peripheral blood and serum measures of inflammation.

Providence Health & Services

150 mg galunisertib administered orally, twice daily (BID) for 14 days followed by 14 days with no study drug (28 days cycle).

150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).

400 mg sorafenib administered orally BID for 28 days.

Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle).

400 mg sorafenib administered orally BID for 28 days.

Placebo

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - hours, EST)

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY2157299 in participants with hepatocellular carcinoma.

A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma

A Randomized Phase 2 Study of LY2157299 Versus LY2157299 - Sorafenib Combination Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

OS defined as the time from the date of randomization to the date of death due to any cause. An overall survival event was defined as death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The number of participants with overall survival events (deaths) is reported.

Population mean (between-subject coefficient variance \[CV %\]) apparent clearance.

Population Vss \[distribution of galunisertib in the body at steady state\] after a single dose of galunisertib.

TTP at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

EORTC QLQ-C30 consists of 30 items covered by 1 of 3 dimensions:

1. Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent).
2. Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much).
3. Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much).

All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.

The EORTC QLQ-HCC-18 was an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30. EORTC QLQ-HCC 18 questionnaire included 8 symptom scales such as abdominal swelling, sex life, fatigue, body image, jaundice, nutrition, pain and fever. Each individual item ranges from 1 to 4, where 1 = "not at all" and 4 = "very much." All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a symptom scale/item represented a high level of symptomatology/problem.

All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.

150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).

150 mg Galunisertib Monotherapy

150 mg Galunisertib + 400 mg Sorafenib Therapy

400 mg Sorafenib + Placebo Therapy

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

South Korea

Hong Kong

China

Taiwan

Thailand

Region of Enrollment

Weight

Height

Tobacco use

Alcohol use

Alcohol drinks per week

Chief Medical Officer

All randomized participants. Censored participants: Galunisertib Monotherapy =5, Galunisertib Plus Sorafenib Therapy = 16 and Sorafenib Plus Placebo Therapy = 7.

Overall Survival (OS): Number of Events

150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).

150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days.

Galunisertib Monotherapy and Galunisertib + Sorafenib Therapy

All randomized participants who received at least one dose of study drug, with evaluable galunisertib PK data. The analyses conducted on galunisertib exposure parameter from both arms combined per the statistical analysis plan, as monotherapy and combination arm showed no difference in galunisertib PK.

Population Pharmacokinetics (PopPK): Mean Population Clearance of Galunisertib

Population Pharmacokinetics (PopPK): Steady State Apparent Volume of Distribution (Vss) of Galunisertib

All randomized participants. Censored participants: Galunisertib Monotherapy =2, Galunisertib Plus Sorafenib Therapy = 15 and Sorafenib Plus Placebo Therapy = 9.

Time to Tumor Progression (TTP)

All randomized participants. Censored participants: Galunisertib Monotherapy =1, Galunisertib Plus Sorafenib Therapy = 8 and Sorafenib Plus Placebo Therapy = 5.

Progression-Free Survival (PFS)

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

Global health status

Functional scale: Physical functioning

Functional scale: Role functioning

Functional Scale: Emotional Functioning

Functional Scale: Cognitive Functioning

Functional Scale: Social Functioning

Symptom Scale: Fatigue

Symptom Scale: Nausea and Vomiting

Symptom scale: Pain

Symptom scale: Dyspnoea

Symptom scale: Insomnia

Symptom scale: Appetite loss

Symptom scale: Constipation

Symptom scale: Diarrhoea

Symptom scale: Financial difficulties

All randomized participants who received at least one dose of study drug and with baseline and post-baseline EORTC QLQ-C30 data for each EORTC QLQ-C30 items.

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Score

Abdominal swelling

Sex Life

Fatigue

Body Image

Jaundice

Nutrition

Pain

Fever

All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC-QLQ HCC-18 data for each EORTC-QLQ HCC-18 items.

Change From Baseline in EORTC QLQ Hepatocellular Carcinoma (HCC-18) Questionnaire Score

150 Milligram (mg) Galunisertib Monotherapy

Overall Study

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gemcitabine

150 mg LY2157299 is administered orally twice daily for 14 days followed by 14 days without study drug (28 day cycle.) Gemcitabine 1000 milligram per square meter will be administered intravenously (IV) on Days 8, 15, and 22 in each cycle (28 day cycle). Participants may continue to receive treatment until discontinuation criteria are met.

The main purpose of this study is to evaluate the safety and side effects of LY2157299 in combination with gemcitabine in Japanese participants with pancreatic cancer that is advanced or has spread to another part of the body.

A Study of LY2157299 in Participants With Pancreatic Cancer That is Advanced or Has Spread to Another Part of the Body

A Phase 1b Study of LY2157299 in Combination With Gemcitabine in Patients With Advanced or Metastatic Unresectable Pancreatic Cancer

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

160mg of enzalutamide is administered orally once a day on days 1-28 of each cycle.

Enzalutamide

150 mg of LY2157299 is administered orally twice a day on days 1-14 of each cycle.

Channing Paller, MD

The primary objective of this study is to compare the progression free survival (PFS) of patients with metastatic castration-resistant prostate cancer treated with enzalutamide in combination with LY2157299 (Arm 1) versus enzalutamide alone (Arm 2).

Study of TGF-β Receptor Inhibitor Galunisertib (LY2157299) and Enzalutamide in Metastatic Castration-resistant Prostate Cancer

Overcoming Drug Resistance in Metastatic Castration-resistant Prostate Cancer With Novel Combination of TGF-β Receptor Inhibitor LY2157299 and Enzalutamide: a Randomized Multi-site Phase II Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose-Escalation Study in Participants With Recurrent Malignant Glioma	NCT01682187	Glioma	LY2157299 Lomustine	18 Years -	Eli Lilly and Company
A Study Combining LY2157299 With Temozolomide-based Radiochemotherapy in Patients With Newly Diagnosed Malignant Glioma	NCT01220271	Glioma	LY2157299 Radiation Temozolomide	18 Years -	Eli Lilly and Company
Study of LY2157299 in Japanese Participants With Cancer	NCT01722825	Neoplasms Neoplasm Metast...	LY2157299	20 Years -	Eli Lilly and Company
A Study of LY2157299 in Participants With Unresectable Hepatocellular Cancer (HCC)	NCT02240433	Hepatocellular ...	LY2157299 Sorafenib	20 Years -	Eli Lilly and Company
ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer	NCT02688712	Rectal Adenocar...	LY2157299 Capecitabine Fluorouracil Tumor specific ...	18 Years -	Providence Health & Services
A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma	NCT02178358	Hepatocellular ...	LY2157299 Sorafenib Placebo	18 Years -	Eli Lilly and Company
A Study of LY2157299 in Participants With Pancreatic Cancer That is Advanced or Has Spread to Another Part of the Body	NCT02154646	Pancreatic Neop...	LY2157299 Gemcitabine	20 Years -	Eli Lilly and Company
Study of TGF-β Receptor Inhibitor Galunisertib (LY2157299) and Enzalutamide in Metastatic Castration-resistant Prostate Cancer	NCT02452008	Prostate Cancer	Enzalutamide LY2157299	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma	NCT02178358	Hepatocellular ...	LY2157299 Sorafenib Placebo	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for ly2157299

Every month we try and update this database with for ly2157299 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ly2157299

Every month we try and update this database with for ly2157299 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ly2157299 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.