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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
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.
Supplied as 5 mg or 10 mg tablets, administered orally, daily for two 28-day cycles.
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
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.
Bordeaux, France
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.
Villejuif, France
Recommended Dose for Phase 2 Studies
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.
Time frame: Baseline up to 6 cycles of 28 days
Clinically Significant Effects (Number of Participants With Adverse Events)
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.
Time frame: Baseline up to 7 months
Progression-Free Survival (PFS)
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.
Time frame: Baseline to disease progression or death or up to 166 days postbaseline
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)]
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.
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Time frame: Baseline to disease progression or death or up to 6 cycles of 28 days
Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702
Time frame: Cycle 1 Day 1 (C1 D1): predose, 0.5, 1, 2, 3, 5, 8 hours postdose and Cycle 1 Day 8 (C1 D8): predose, 0.5, 1, 2, 3, 5, and 8 hours postdose of 28-day cycle
Pharmacokinetics, Area Under the Concentration Time Curve (AUC)
AUC from time 0 to 8 hours (AUC0-8) and AUC from time 0 to infinity (AUC0-∞).
Time frame: Cycle 1 Days 1 (C1 D1) and Cycle 1 Day 8 (C1 D8) of 28-day cycle
Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)]
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.
Time frame: Baseline up to 112 Days