Cancer
Conditions
Keywords
Advanced Cancer, Metastatic Cancer, p70s6 inhibitor
Brief summary
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.
Interventions
DRUGLY2584702
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.
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histological or cytological evidence of a diagnosis of advanced and/or metastatic cancer (solid tumors) that is refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists. * Have the presence of disease amenable to efficacy assessment as defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Japanese patients who have advanced non-measurable disease with elevation of a validated tumor marker may be eligible, if discussed and agreed upon by the investigator and Lilly. * Have adequate organ function including: * Hematologic: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10\^9/liter (L), platelets greater than or equal to 100 x 10\^9/L, and hemoglobin greater than or equal to 9 gram/deciliter (g/dL) (transfusions are not allowed prior to enrollment within 2 weeks). * Hepatic: Bilirubin less than or equal to 1.5 times upper limit of normal (ULN), alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN, or 5 times ULN for patients with hepatic metastases. Patients with bone metastases may enter with alkaline phosphatase values less than 5 times ULN, as long as other hepatic parameters meet inclusion criteria. * Renal: Serum creatinine less than or equal to 1.5 times ULN. * Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group scale * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy prior to study enrollment and recovered from the acute effects of therapy. * Have an estimated life expectancy of 12 weeks or greater * Are able to swallow capsules
Exclusion criteria
* Have received treatment within 4 weeks of the initial dose of study drug with a drug that has not received regulatory approval for any indication. * Have serious preexisting medical conditions or serious concomitant systemic disorders that, in the opinion of the investigator, would preclude participation in this study. * Prior clinical history of tuberculosis (patient doubt tuberculosis is screening required), and positive test results in hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb) (screening required). * Have symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without history of CNS metastasis is not required. * Have hematologic malignancies, or lymphoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Effects | Baseline through 30 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tumor Response | Baseline to study completion up to Day 183 | 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. |
| Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2584702 | Cycle 1 Day 1: Predose, 0.5,1,2,3,5,8,12 hours; Cycle 1 Day 2:24 and 36 hours; Cycle 1 Day 3: Predose sample (before first dose on day 3); Cycle 1 Day 10: Predose,0.5,1,2,3,5,8,12 hours;Cycle 1 Day 17: Predose;Cycle 1 Day24: Predose;Cycle 2 Day 1: Predose | AUC of single dose is AUC(0-12hours), and AUC of multiple doses is AUC during one dosing interval at steady state. |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY2584702 | Cycle 1 Day 1: Predose, 0.5,1,2,3,5,8,12 hours; Cycle 1 Day 2:24 and 36 hours; Cycle 1 Day 3: Predose sample (before first dose on day 3); Cycle 1 Day 10: Predose,0.5,1,2,3,5,8,12 hours;Cycle 1 Day 17: Predose;Cycle 1 Day24: Predose;Cycle 2 Day 1: Predose | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50 mg LY2584702 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 | 3 |
| 75 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 | 6 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Progressive Disease | 3 | 6 |
Baseline characteristics
| Characteristic | 75 mg LY2584702 | 50 mg LY2584702 | Total |
|---|---|---|---|
| Age, Continuous | 64.07 years STANDARD_DEVIATION 4.15 | 66.44 years STANDARD_DEVIATION 7.17 | 64.86 years STANDARD_DEVIATION 5 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Prior to Cycle 1 0 - Fully active | 6 Participants | 2 Participants | 8 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Prior to Cycle 1 1 - Ambulatory, restricted strenuous activity | 0 Participants | 1 Participants | 1 Participants |
| Pathological Diagnosis Adenocarcinoma, Colon | 2 Participants | 1 Participants | 3 Participants |
| Pathological Diagnosis Adenocarcinoma, Esophageal | 1 Participants | 1 Participants | 2 Participants |
| Pathological Diagnosis Adenocarcinoma, Gastric | 0 Participants | 1 Participants | 1 Participants |
| Pathological Diagnosis Carcinoid Tumor, not otherwise specified (NOS) | 1 Participants | 0 Participants | 1 Participants |
| Pathological Diagnosis Carcinoma, Esophagus | 1 Participants | 0 Participants | 1 Participants |
| Pathological Diagnosis Gastrointestinal Stromal Tumors | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 6 |
Outcome results
Primary
Number of Participants With Clinically Significant Effects
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.
Time frame: Baseline through 30 days
Population: All participants who were enrolled in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg LY2584702 | Number of Participants With Clinically Significant Effects | 0 Participants |
| 75 mg LY2584702 | Number of Participants With Clinically Significant Effects | 0 Participants |
Secondary
Number of Participants With Tumor Response
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.
Time frame: Baseline to study completion up to Day 183
Population: All participants who were enrolled in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg LY2584702 | Number of Participants With Tumor Response | 0 Participants |
| 75 mg LY2584702 | Number of Participants With Tumor Response | 0 Participants |
Secondary
Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2584702
AUC of single dose is AUC(0-12hours), and AUC of multiple doses is AUC during one dosing interval at steady state.
Time frame: Cycle 1 Day 1: Predose, 0.5,1,2,3,5,8,12 hours; Cycle 1 Day 2:24 and 36 hours; Cycle 1 Day 3: Predose sample (before first dose on day 3); Cycle 1 Day 10: Predose,0.5,1,2,3,5,8,12 hours;Cycle 1 Day 17: Predose;Cycle 1 Day24: Predose;Cycle 2 Day 1: Predose
Population: All participants who were enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg LY2584702 | Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2584702 | 5100 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 58 |
| 75 mg LY2584702 | Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2584702 | 4990 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
| 50 mg LY2584702 Multiple Doses | Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2584702 | 8020 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 66 |
| 75 mg LY2584702 Multiple Doses | Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2584702 | 10300 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY2584702
Time frame: Cycle 1 Day 1: Predose, 0.5,1,2,3,5,8,12 hours; Cycle 1 Day 2:24 and 36 hours; Cycle 1 Day 3: Predose sample (before first dose on day 3); Cycle 1 Day 10: Predose,0.5,1,2,3,5,8,12 hours;Cycle 1 Day 17: Predose;Cycle 1 Day24: Predose;Cycle 2 Day 1: Predose
Population: All participants who were enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg LY2584702 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2584702 | 805 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| 75 mg LY2584702 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2584702 | 732 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| 50 mg LY2584702 Multiple Doses | Pharmacokinetics: Maximum Concentration (Cmax) of LY2584702 | 1140 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 78 |
| 75 mg LY2584702 Multiple Doses | Pharmacokinetics: Maximum Concentration (Cmax) of LY2584702 | 1400 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 47 |