Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Oral dose escalation starting at 25 milligrams (mg), daily for 28 day cycles in Part A; oral dose escalation starting at 50 mg, twice daily for 28 day cycles in Part B; oral dose with schedule determined by Parts A and B will be administered in Part C (dose confirmation).

Part A: Participants received 25 mg, 50 mg, 100 mg and 200 mg once daily (QD) and 300 mg twice daily (BID) of LY2584702 capsule, for a 28-day cycle during Part A of the study until the criteria for maximum tolerated dose (MTD) were met.

Part B: Participants received 50 mg, 75 mg and 100 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until the criteria for maximum tolerated dose (MTD) were met.

LY2584702

Call 1-877-CTLILLY (1-817-285-4559) or 1-317-615-4559 Mon-Fri Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The main purpose of this trial is to determine a recommended Phase 2 dose of LY2584702 that may be safely administered to participants with advanced/metastatic cancer.

A Study of LY2584702 in Participants With Advanced Cancer

A Phase I Study of LY2584702 in Patient With Advanced or Metastatic Cancer

Based on the maximum tolerated dose (MTD): highest dose where \<33% participants experienced a dose-limiting toxicity (DLT). DLTs were adverse events (AEs) during Cycle 1 that met any 1 of the following criteria using National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE) grading: any ≥Grade 3 nonhematological toxicity (except nausea/vomiting, diarrhea or hypophosphatemia without maximal symptomatic/prophylactic treatment) that was not related to study disease, any ≥Grade 3 thrombocytopenia with bleeding, any Grade 4 hematological toxicity of \>5 days duration or any febrile neutropenia. Investigators, together with the sponsor, could declare a DLT during Cycle 1 if a participant experienced increasing toxicity and it was clear that further treatment would expose the participant to excessive risk. The MTD was below the level required for efficacy, therefore, the study was terminated early and the recommended Phase 2 dose was not calculated.

Cmax results on Day 1 and on Day 8 (steady state) are reported.

Tumor response was defined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria. Complete Response (CR) was the disappearance of all target and non-target lesions and normalization of tumor marker levels of non-target lesions; Partial Response (PR) was at least a 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) was at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions; Stable Disease (SD) was small changes that did not meet above criteria including persistence of 1 or more non-target lesion(s).

Results for AUC from time 0 to infinity \[AUC(0-inf)\] and AUC from time 0 to 24 hours \[AUC(0-24)\] on Day 1 and Day 8 (steady state) are reported for participants on a QD LY2584702 dosing regimen.

Results for AUC from time 0 to infinity \[AUC(0-inf)\] and AUC from time 0 to 12 hours \[AUC(0-12)\] on Day 1 and Day 8 (steady state) are reported for participants with a BID LY2584702 dosing regimen.

Eli Lilly and Company

Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.

Participants received 25 milligrams (mg) of LY2584702 orally as a capsule, once daily (QD) for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

25 mg LY2584702 QD

Participants received 50 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

50 mg LY2584702 QD

Participants received 100 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

100 mg LY2584702 QD

Participants received 200 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

200 mg LY2584702 QD

Participants received 50 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

50 mg LY2584702 BID

Participants received 75 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

75 mg LY2584702 BID

Participants received 100 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

100 mg LY2584702 BID

Participants received 300 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

300 mg LY2584702 BID

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

United States

Region of Enrollment

All participants who received at least 1 dose of study drug.

Part C of the study was terminated because exposure at the maximum tolerated dose (MTD) was determined to be below the level required for efficacy.

Chief Medical Officer

Participants received 25 mg, 50 mg, 100 mg and 200 mg once daily (QD) and 300 mg twice daily (BID) of LY2584702 capsule, for a 28-day cycle during Part A of the study until the criteria for maximum tolerated dose (MTD) were met.

Part A

Participants received 50 mg, 75 mg and 100 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until the criteria for maximum tolerated dose (MTD) were met.

Part B

Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD)

Day 1

Day 8

All participants who received at least 1 dose of study drug and had evaluable Cmax data. In 300 mg LY2584702 BID group data was not analyzed for Cmax day 8 due to insufficient participants at the specified time point.

Pharmacokinetics, Maximum Plasma Concentration (Cmax)

Complete Response

Partial Response

Stable Disease

Progressive Disease

Number of Participants With Tumor Response

AUC(0-inf), Day 1

AUC(0-24), Day 1

AUC(0-24), Day 8

All participants who received at least 1 dose of study drug \[QD dosing regimen (Part A)\].

Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing

AUC(0-12), Day 1

AUC(0-12), Day 8

Participants received 50 milligrams (mg) LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

All participants who received at least 1 dose of study drug \[BID dosing regimen (Part A or B)\] and had evaluable AUC data. In 300 mg LY2584702 BID group data was not analyzed for AUC(0-12) day 8 due to insufficient participants at the specified time point.

Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing

Overall Study

Dose escalation starting at 50 milligram (mg). On Day 1, subjects will receive a single oral dose. After a two-day observation period, subjects will receive oral doses twice daily for a 28-day cycle.

Patients may continue 28-day cycles of twice daily dosing until discontinuation criteria are met.

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)

The purpose of this study is to assess the safety and tolerability of LY2584702 in Japanese patients with advanced and/or metastatic solid tumors for which no proven effective therapy exists.

A Study of LY2584702 in Solid Tumors

A Phase 1 Study of LY2584702 in Japanese Patients With Solid Tumors

A clinically significant effect was any event that was a dose-limiting toxicity event (DLT). DLT was defined as an adverse event related to LY2584702 during Cycle 1 (Day 1 to Day 30) that fulfills any one of the following criteria; Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 non-hematological toxicity; platelet count \<50.0 x 10\^9/Liter (L) with bleeding; CTCAE Grade 4 platelet count decreased; neutrophil count \<0.5 x 10\^9/L lasting for 5 days or longer; any febrile neutropenia; CTCAE Grade 4 anemia; participant risk due to increasing toxicity.

Tumor response was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. Complete Response (CR) is disappearance of all target lesions; Partial Response (PR) is ≥30% decrease in sum of longest diameter of target lesions.

AUC of single dose is AUC(0-12hours), and AUC of multiple doses is AUC during one dosing interval at steady state.

50 milligram (mg) LY2584702 single oral dose on Day 1. After a two-day observation period, participants received oral doses twice daily for a 28-day cycle

50 mg LY2584702

75 mg LY2584702 single oral dose on Day 1. After a two-day observation period, participants received oral doses twice daily for a 28-day cycle

75 mg LY2584702

Race (NIH/OMB)

Japan

Adenocarcinoma, Colon

Adenocarcinoma, Esophageal

Adenocarcinoma, Gastric

Carcinoid Tumor, not otherwise specified (NOS)

Carcinoma, Esophagus

Gastrointestinal Stromal Tumors

Pathological Diagnosis

0 - Fully active

1 - Ambulatory, restricted strenuous activity

Classifies participants according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death).

Eastern Cooperative Oncology Group (ECOG) Performance Status Prior to Cycle 1

All participants who were enrolled in the study.

Number of Participants With Clinically Significant Effects

50 milligram (mg) LY2584702 single oral dose on Day 1

50 mg LY2584702 Single Dose

75 mg LY2584702 single oral dose on Day 1

75 mg LY2584702 Single Dose

50 mg LY2584702 oral doses twice daily for a 28-day cycle

50 mg LY2584702 Multiple Doses

75 mg LY2584702 oral doses twice daily for a 28-day cycle

75 mg LY2584702 Multiple Doses

Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2584702

Pharmacokinetics: Maximum Concentration (Cmax) of LY2584702

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Carcinoma, Renal Cell

Neuroendocrine Tumors

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplastic Processes

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Renal Cell Carcinoma

Neuroendocrine Tumor

Clear Cell Renal Cell Carcinoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Everolimus

Erlotinib Hydrochloride

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Tyrosine Kinase Inhibitors

Tyrosine

Participants received 50 mg LY2584702 once daily (QD )+ 150 mg Erlotinib QD, 50 mg LY2584702 twice daily (BID) + 150 mg Erlotinib QD, 100 mg LY2584702 BID + 150 mg Erlotinib QD and 75 mg LY2584702 BID + 150 mg Erlotinib QD.

Participants received 50 mg LY2584702 QD + 10 mg Everolimus QD, 100 mg LY2584702 QD + 10 mg Everolimus QD and 50 mg LY2584702 BID + 10 mg Everolimus QD.

Supplied as 25 milligrams (mg) and 100 mg capsules, administered orally for two 28-day cycles.

Supplied as 25 mg, 100 mg, or 150 mg tablets, administered orally, daily for two 28-day cycles.

Starting dose is 150mg. Doses may be decreased in 50mg increments if necessary due to toxicity.

Erlotinib

Supplied as 5 mg or 10 mg tablets, administered orally, daily for two 28-day cycles.

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

Study I3G-MC-JGCB (JGCB) is a multicenter, nonrandomized, open-label, dose-escalation Phase 1b study of LY2584702 in combination with either erlotinib or everolimus.

Study JGCB will consist of the following parts:

Part 1 - Dose Escalation to maximum tolerated dose in each arm.

Arm A - LY2584702 + Erlotinib in participants with advanced or metastatic cancer.

Arm B - LY2584702 + Everolimus in participants with advanced or metastatic cancer.

Part 2 - Dose Confirmation of maximum tolerated dose from each arm in Part 1.

Arm A - LY2584702 + Erlotinib in participants with advanced or metastatic non-small cell lung cancer.

Arm B - LY2584702 + Everolimus in participants with advanced renal cell carcinoma after treatment failure with sunitinib or sorafenib, or advanced neuroendocrine tumors.

A Study of LY2584702 With Erlotinib or Everolimus in Participants With Solid Tumors

A Phase 1b Trial of LY2584702 in Combination With Erlotinib or Everolimus in Patients With Solid Tumors

The recommended dose for the Phase 2 (Dose Confirmation Phase) study was determined by safety assessment. Doses were escalated following the assessment for toxicity based on Common Terminology Criteria for Adverse Events (CTCAE v4.0). Any adverse events (AE) that were possibly related to LY2584702 were considered toxicities. The Phase 2 dose of LY2584702 was not determined due to unacceptable toxicities of LY2584702 in combination with erlotinib or everolimus in Phase 1 of the study.

Clinically significant events were defined as serious adverse events (SAEs) and other non-SAEs regardless of causality. A summary of serious and other non SAEs regardless of causality is located in the Reported Adverse Event module.

PFS was defined as the time from the date of enrollment to the date of objectively determined progressive disease (PD) or death whichever comes first. Censoring of PFS was defined as participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective assessment; for participants who received subsequent systematic anticancer therapy (after discontinuation from study treatment) prior to objectively determined disease progression, PFS was censored at the date of the last objective progression-free disease assessment prior to post discontinuation of therapy. PFS was not analyzed due to different tumor types and different doses.

Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions.

AUC from time 0 to 8 hours (AUC0-8) and AUC from time 0 to infinity (AUC0-∞).

BOR was determined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of LD of target lesions and minimum 5 mm increase over nadir. SD was defined as small changes that did not meet above criteria.

Deaths due to progressive disease were not considered to be serious adverse events (SAE) unless the investigator deemed them to be related to the use of the study drug.

50 milligram (mg) LY2584702 administered orally once daily (QD) plus 150 mg erlotinib administered orally QD for 2 28-day cycles.

Arm A - 50 mg LY2584702 QD + 150 mg Erlotinib QD

50 mg LY2584702 administered orally twice daily BID plus 150 mg erlotinib administered orally QD for 2 28-day cycles.

Arm A - 50 mg LY2584702 BID + 150 mg Erlotinib QD

100 mg LY2584702 administered orally BID plus 150 mg erlotinib administered orally QD for 2 28-day cycles.

Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD

75 mg LY2584702 administered orally BID plus 150 mg erlotinib administered orally QD for 2 28-day cycles.

Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD

50 mg LY2584702 administered orally QD plus 150 mg everolimus administered orally QD for 2 28-day cycles.

Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD

100 mg LY2584702 administered orally QD plus 150 mg everolimus administered orally QD for 2 28-day cycles.

Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD

50 mg LY2584702 administered orally BID plus 150 mg everolimus administered orally QD for 2 28-day cycles.

Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD

50 milligrams (mg) LY2584702 administered orally once daily (QD) plus 150 mg erlotinib administered orally QD for two 28-day cycles.

50 mg LY2584702 administered orally twice daily (BID) plus 150 mg erlotinib administered orally QD for two 28-day cycles.

100 mg LY2584702 administered orally BID plus 150 mg erlotinib administered orally QD for two 28-day cycles.

75 mg LY2584702 administered orally BID plus 150 mg erlotinib administered orally QD for two 28-day cycles.

50 mg LY2584702 administered orally QD plus 10 mg everolimus administered orally QD for two 28-day cycles.

100 mg LY2584702 administered orally QD plus 10 mg everolimus administered orally QD for two 28-day cycles.

50 mg LY2584702 administered orally BID plus 10 mg everolimus administered orally QD for two 28-day cycles.

France

Participants received at least 1 dose of study drug.

Study terminated early. Dose confirmation, Part B, was not initiated.

Escalating doses of LY2584702 began with 50 milligrams (mg) and increased up to 200 mg total daily dose were administered orally in combination with erlotinib.

LY2584702 + Erlotinib

Escalating doses of LY2584702 began with 50 mg and increased up to 100 mg total daily dose were administered orally in combination with everolimus.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of LY2584702 in Participants With Advanced Cancer	NCT01394003	Advanced Cancer	LY2584702	18 Years -	Eli Lilly and Company
A Study of LY2584702 in Participants With Advanced Cancer	NCT01394003	Advanced Cancer	LY2584702	18 Years -	Eli Lilly and Company
A Study of LY2584702 in Solid Tumors	NCT01241461	Cancer	LY2584702	20 Years -	Eli Lilly and Company
A Study of LY2584702 With Erlotinib or Everolimus in Participants With Solid Tumors	NCT01115803	Metastases, Neo... Carcinoma, Non-... Renal Cell Carc... Neuroendocrine ...	LY2584702 Erlotinib Everolimus	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for ly2584702

Every month we try and update this database with for ly2584702 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 ly2584702

Every month we try and update this database with for ly2584702 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 ly2584702 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.