Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Carcinoma

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Central Nervous System Depressants

Other Dietary Supplements

Gemcitabine

Carboplatin

Benzocaine

Antimetabolites

Tannic Acid

Cohort 1: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 milligrams per square meter (mg/m\^2) administered intravenously (IV) over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3..

Cohort 1: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.

Cohort 2: Cycles 1-6 (21 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m\^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.

Cohort 2: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.

Arm A: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m\^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.

Arm A: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.

Arm B: Cycles 1-6 (21 day cycles)- Placebo administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m\^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.

Arm B: Cycle 7+ (28 day cycles)- Placebo administered orally on days 1-14 to maintain blind.

LY2228820

Placebo

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

A study for women with ovarian cancer that has returned at least 6 months after platinum-based chemotherapy.

Phase 1b is unblinded and will have a small number of participants that will take LY2228820 plus gemcitabine and carboplatin to test the safety of the combination and determine a recommended dose for the Phase 2 portion.

Phase 2 will be blinded and all study participants will receive carboplatin and gemcitabine. Participants of one group will receive LY2228820, and the other group will receive placebo.

If the participant achieves at least stable disease, there is a maintenance phase following the first 6 cycles. The participant will take either LY2228820 or placebo. The participant will continue therapy until disease progression or other discontinuation criteria are fulfilled.

A Study LY2228820 for Recurrent Ovarian Cancer

A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38 MAPK Inhibitor, Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin for Women With Platinum-Sensitive Ovarian Cancer

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.

Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).

PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (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.

Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.

PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.

The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = "not at all" and 4 = "very much." Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.

Eli Lilly and Company

All participants who received at least one dose of drug.

Cohort 1: LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6)

Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10

Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3

Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin

Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3

Cohort 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin

Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3

Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin

Arm B: Placebo orally every 12 hrs. on Days 1-10

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3

Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin

Cohort 1:LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6).

Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10.

Carboplatin area under the concentration curve administered intravenously (IV) over 30 minutes (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3.

Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6).

Phase 1b: Cohort 1: LY2228820 +Gemcitabine+Carboplatin

Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6).

Gemcitabine 1000 mg/m2 administered IV over 30 min on Days 3 and 10.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3.

Cohort 2:LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).

Phase 1b: Cohort 2: LY2228820 +Gemcitabine+Carboplatin

Arm A:LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6).

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3.

Arm A:LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).

Arm A: LY2228820 + Gemcitabine + Carboplatin

Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle (Cycles 1-6).

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3.

Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).

Arm B Placebo + Gemcitabine +Carboplatin

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Belgium

United States

Australia

Germany

Region of Enrollment

Received Maintenance Therapy

Did Not Receive Maintenance Therapy

Data Missing or Not Collected

Maintenance therapy as part of or after first line platinum regimen data was used as a cofactor in the analysis of Progression Free Survival (PFS). Zero participants analyzed for Phase 1 portion of the study.Data was collected only from participants treated in the Phase 2 portion of the study.

Maintenance Therapy as a Part of or After a First Line Platinum Regimen

All participants who received at least one dose of study drug.

Chief Medical Officer

Cohort 1 : LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6)

Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10

Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3

Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3

Cohort 1 and 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

LY2228820 + Gemcitabine + Carboplatin

All participants who received at least one dose of study drug in Phase 1b.

Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])

Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of 21-day cycles.

Gemcitabine 1000 mg/m2 IV over 30 min on Days 3 and 10 of 21-day cycles.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of 21-day cycles.

Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)

LY2228820 + Gemcitabine +Carboplatin

Arm B: Placebo orally every 12 hrs. on Days 1-10 of 21-day cycles.

Gemcitabine 1000 mg/m2 IV over 30 min on Days 3 and 10 of 21-day cycles.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. n Day 3 of 21-day cycles.

Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)

Placebo + Gemcitabine + Carboplatin

All participants in Phase 2 who received at least one dose of study drug.

Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin

Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle.

Gemcitabine 1000 mg/m2 IV over 30 min.(+ 15 min.) on Days 3 and 10 of a 21-day cycle.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day.

Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).

Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle.

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.

Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)

All participants who received at least one dose of study drug in Phase 2.

Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)

Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle.

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day.

Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).

All participants in Phase 2 who received at least one dose of drug.

Phase 2: Overall Survival

Cycle 1 Day 1

Cycle 1 Day 3

Cycle 1 Day 10

Cycle 2 Day 10

Cycle 7 Day 3

Phase 1b (Cohort 1) and Phase 2 (Arm A): LY2228820 200 mg administered orally every 12 hours on Days 1-10, Cycles 1-6 of a 21 day cycle.

.

200 mg LY2228820

Phase 1b (Cohort 2) and Phase 2 (Arm A) in the maintenance portion with LY2228820 300 mg administered orally every 12 hours on Days 1-14 Cycle 7+ of a 28-day cycle.

300 mg LY2228820

All participants in Phase 1b and Phase 2 who received at least one dose of study drug and had evaluable PK data.

Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820

Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle.

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day.

Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle.

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.

Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

All participants in Phase 2 who received at least one dose of study drug and had at least one post baseline assessment.

Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score

Cohort 1:LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6).

Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 of a 21-day cycle.

Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.

Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).

Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 of a 21-day cycle.

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.

Cohort 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).

Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle.

Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.

Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.

Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Tamoxifen

Aromatase Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Tamoxifen will be administered daily orally

Patients will receive study medication until disease progression or unacceptable toxicity

Tamoxifen will be administered daily orally LY2228820 dimesylate (Ralimetinib) will be administered orally

Patients will receive study medication until disease progression or unacceptable toxicity

Ralimetinib (LY2228820 dimesylate)

Christelle LEVY, MD

Metastatic breast cancer (MBC) remains an incurable disease and despite an improvement of the effect of systemic treatments. After relapse on first-line non-steroidal aromatase inhibitor, current clinical practice and treatment guidelines include tamoxifen, fulvestrant (an ER antagonist) and exemestane as available options (NCCN treatment guidelines 2012), but in this context of resistance, their efficacy are poor.

Some results confirm the possibility to improve the efficacy of tamoxifen in metastatic setting by a combination with therapy targeting signal transduction pathways. Other transduction pathways seem to be involved in endocrine sensitivity/resistance, such as RAS/RAF/MEK/MAK pathway.

LY2228820 inhibits the activity of p38 MAPK (selective inhibitor of the α and β isoforms of p38 MAPK in vitro) and reduces phosphorylation of its cellular target, MAPK-activated protein kinase 2 (MAPKAP-K2).

A Multicenter Trial Assessing the Efficacy and Safety of tamOxifen Plus LY2228820 in Advanced or Metastatic Breast Cancer Progressing on aromatasE Inhibitors

A Randomized Open-label Phase II Multicenter Trial Assessing the Efficacy and Safety of tamOxifen Plus LY2228820 in Advanced or Metastatic Breast Cancer Progressing on aromatasE Inhibitors

Adverse events description and grade in all participants

National Cancer Institute, France

ARC Foundation for Cancer Research

Centre Francois Baclesse

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

addition of LY2228820 to standard radiotherapy and concomitant treatment by temozolomide (TMZ).

LY2228820 will be administered orally for two 28 day cycles, from one week before the beginning of radiotherapy, and during standard chemoradiotherapy. Three dose levels of LY2228820 will be tested.

After a 4 week break after concomitant treatment, patient were then received up to 6 cycles of adjuvant TMZ according to the standard 5-day schedule every 28 days .

radiotherapy

Xavier DURANDO, Pr

Glioblastomas are extremely resistant to treatment, including radiotherapy and/or chemotherapy. Mitogen-activated protein kinase (MAPK) cascades are key signaling pathways involved in the regulation of normal cell proliferation, survival and differentiation. Activation of p38 MAPK has been associated with a poor prognosis among patients with glioblastoma during the temozolomide (TMZ) era and represents a compensatory response by tumor cell to environmental stress such as radiation or chemotherapy.

LY2228820 is a potent and selective inhibitor of p38 MAPK, and reduces phosphorylation of its cellular target, MAPK-activated protein kinase 2 (MAPKAPK-2) . LY2228820 is a good candidate to target malignant glioma resistance to the gold standard treatment combining radiation and TMZ by acting on both tumor and stromal cells.

The primary objectives of this study were to determine the recommended dose of LY2228820 in combination with TMZ and radiotherapy during chemoradiotherapy period (phase I) and to estimate the 6-month progression free survival (PFS) rate of patients treated with LY2228820 when administered at the recommended dose in combination with radiotherapy and concomitant TMZ (phase II)

Study of LY2228820 With Radiotherapy Plus Concomitant TMZ in the Treatment of Newly Diagnosed Glioblastoma

Phase I/II Study of LY2228820 With Radiotherapy Plus Concomitant TMZ in the Treatment of Newly Diagnosed Glioblastoma

defined as the highest dose tested in which a dose limiting toxicity (DLT) is experienced by no more than 33% of patients during chemoradiotherapy period.

disease progression assessed per Response Assessment in Neuro-Oncology (RANO) criteria

in tumor and stromal cells and Peripheral Blood Mononucleated Cells (PBMCs)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study LY2228820 for Recurrent Ovarian Cancer	NCT01663857	Epithelial Ovar... Fallopian Tube ... Primary Periton...	LY2228820 Carboplatin Placebo Gemcitabine	18 Years -	Eli Lilly and Company
A Multicenter Trial Assessing the Efficacy and Safety of tamOxifen Plus LY2228820 in Advanced or Metastatic Breast Cancer Progressing on aromatasE Inhibitors	NCT02322853	Postmenopausal Metastatic Brea...	Tamoxifen Ralimetinib (LY...	18 Years -	Centre Francois Baclesse
Study of LY2228820 With Radiotherapy Plus Concomitant TMZ in the Treatment of Newly Diagnosed Glioblastoma	NCT02364206	Adult Glioblast...	LY2228820 Temozolomide radiotherapy	18 Years - 75 Years	Centre Jean Perrin

Spots Global Cancer Trial Database for ly2228820

Every month we try and update this database with for ly2228820 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 ly2228820

Every month we try and update this database with for ly2228820 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 ly2228820 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.