Back to resultsA Study of LY2584702 With Erlotinib or Everolimus in Participants With Solid Tumors
Primary Purpose
Metastases, Neoplasm, Carcinoma, Non-small Cell Lung, Renal Cell Carcinoma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LY2584702
Erlotinib
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Metastases, Neoplasm focused on measuring Advanced Cancer, Metastatic Cancer, Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Neuroendocrine Tumors
Eligibility Criteria
Inclusion Criteria:
- Dose Escalation portion (Part 1): have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease (including Non-Hodgkin's Lymphoma) for which no proven effective therapy exists.
Dose Confirmation portion (Part 2): have histological or cytological evidence of:
- Arm A: advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
- Arm B: advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib, or advanced neuroendocrine tumors.
Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma.
- Dose Escalation portion (Part 1): participants may have measurable or nonmeasurable disease.
- Dose Confirmation portion (Part 2): participants must have measurable disease.
Have adequate organ function including:
- Hematologic: absolute neutrophil count (ANC) greater than or equal to 1.5 x 10⁹/liters (L), platelets greater than or equal to 100 x 10⁹/L, and hemoglobin greater than or equal to 8 grams/deciliter (g/dL).
- Hepatic: bilirubin less than or equal to 1.5 times upper limits of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling less than or equal to 5 times ULN are acceptable. Participants with bone metastases may enter with alkaline phosphatase values less than or equal to 5 times ULN, as long as other hepatic parameters meet inclusion criteria.
- Renal: Serum creatinine less than or equal to 1.5 times ULN or calculated creatinine clearance >45 milliliter/minute (ml/mn).
- Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 2 weeks (3 weeks for myelosuppressive agents) prior to study enrollment, and have recovered from the acute effects of therapy. At the discretion of the investigator, participants with prostate cancers progressing under luteinizing hormone-releasing hormone (LHRH) agonists therapy, and participants with adrenal carcinomas using mitotane, may have that treatment continued while receiving study drug.
Exclusion Criteria:
- Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively.
- Have serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study.
- Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable and asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastasis is not required.
- Concomitant treatment by strong cytochrome P450 (CYP) 3A4 inhibitors or CYP3A4 inducers.
- Have an acute or chronic leukemia.
- Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug. In addition, recipients of an allogeneic stem-cell transplant must have discontinued immunosuppressive therapy at least 24 hours before study drug administration with no more than Grade 1 acute graft-versus-host disease.
- For Dose Confirmation portion (Part 2): have previously received erlotinib for Arm A or everolimus for Arm B.
Sites / Locations
- 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.
- 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.
- 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.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A: LY2584702 + Erlotinib
Arm B: LY2584702 + Everolimus
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702
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-∞).
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01115803
Brief Title
A Study of LY2584702 With Erlotinib or Everolimus in Participants With Solid Tumors
Official Title
A Phase 1b Trial of LY2584702 in Combination With Erlotinib or Everolimus in Patients With Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Terminated
Why Stopped
Primary objective has been met; safety and pharmacokinetics have been characterized.
Study Start Date
March 2010 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastases, Neoplasm, Carcinoma, Non-small Cell Lung, Renal Cell Carcinoma, Neuroendocrine Tumors
Keywords
Advanced Cancer, Metastatic Cancer, Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Neuroendocrine Tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: LY2584702 + Erlotinib
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm B: LY2584702 + Everolimus
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
LY2584702
Intervention Description
Supplied as 25 milligrams (mg) and 100 mg capsules, administered orally for two 28-day cycles.
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Intervention Description
Supplied as 5 mg or 10 mg tablets, administered orally, daily for two 28-day cycles.
Primary Outcome Measure Information:
Title
Recommended Dose for Phase 2 Studies
Description
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
Secondary Outcome Measure Information:
Title
Clinically Significant Effects (Number of Participants With Adverse Events)
Description
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
Title
Progression-Free Survival (PFS)
Description
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
Title
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)]
Description
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.
Time Frame
Baseline to disease progression or death or up to 6 cycles of 28 days
Title
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
Title
Pharmacokinetics, Area Under the Concentration Time Curve (AUC)
Description
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
Title
Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)]
Description
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
Other Pre-specified Outcome Measures:
Title
Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation
Time Frame
Within 30 days of study drug discontinuation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Dose Escalation portion (Part 1): have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease (including Non-Hodgkin's Lymphoma) for which no proven effective therapy exists.
Dose Confirmation portion (Part 2): have histological or cytological evidence of:
Arm A: advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
Arm B: advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib, or advanced neuroendocrine tumors.
Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma.
Dose Escalation portion (Part 1): participants may have measurable or nonmeasurable disease.
Dose Confirmation portion (Part 2): participants must have measurable disease.
Have adequate organ function including:
Hematologic: absolute neutrophil count (ANC) greater than or equal to 1.5 x 10⁹/liters (L), platelets greater than or equal to 100 x 10⁹/L, and hemoglobin greater than or equal to 8 grams/deciliter (g/dL).
Hepatic: bilirubin less than or equal to 1.5 times upper limits of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling less than or equal to 5 times ULN are acceptable. Participants with bone metastases may enter with alkaline phosphatase values less than or equal to 5 times ULN, as long as other hepatic parameters meet inclusion criteria.
Renal: Serum creatinine less than or equal to 1.5 times ULN or calculated creatinine clearance >45 milliliter/minute (ml/mn).
Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 2 weeks (3 weeks for myelosuppressive agents) prior to study enrollment, and have recovered from the acute effects of therapy. At the discretion of the investigator, participants with prostate cancers progressing under luteinizing hormone-releasing hormone (LHRH) agonists therapy, and participants with adrenal carcinomas using mitotane, may have that treatment continued while receiving study drug.
Exclusion Criteria:
Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively.
Have serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study.
Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable and asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastasis is not required.
Concomitant treatment by strong cytochrome P450 (CYP) 3A4 inhibitors or CYP3A4 inducers.
Have an acute or chronic leukemia.
Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug. In addition, recipients of an allogeneic stem-cell transplant must have discontinued immunosuppressive therapy at least 24 hours before study drug administration with no more than Grade 1 acute graft-versus-host disease.
For Dose Confirmation portion (Part 2): have previously received erlotinib for Arm A or everolimus for Arm B.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM - 5PM Eastern Time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
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.
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
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.
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
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.
City
Villejuif
ZIP/Postal Code
94805
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
24456794
Citation
Hollebecque A, Houede N, Cohen EE, Massard C, Italiano A, Westwood P, Bumgardner W, Miller J, Brail LH, Benhadji KA, Soria JC. A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with erlotinib or everolimus in patients with solid tumours. Eur J Cancer. 2014 Mar;50(5):876-84. doi: 10.1016/j.ejca.2013.12.006. Epub 2014 Jan 20.
Results Reference
derived
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A Study of LY2584702 With Erlotinib or Everolimus in Participants With Solid Tumors
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