A Study of LY2584702 in Participants With Advanced Cancer

Study Overview
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Brief Summary
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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.

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

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: LY2584702


Participation Criteria
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Eligibility Criteria
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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. Participants 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 the sponsor Participants entering Part C of the study must have a tumor that is safely amenable to 2 biopsies (one pre-treatment and one on-treatment biopsy for the same tumor). Participants in Part C of the study must agree to biopsy procedures at time of consent Have adequate hematologic, renal, and hepatic organ function Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy (with the exception of continuing gonadotropic releasing hormone (GnRH) agonist therapy for participants with prostate cancer, or anti-estrogen therapy [for example, an aromatase inhibitor] for participants with breast cancer), or other investigational therapy for at least 3 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy Are reliable and willing to be available for the duration of the study and are willing to follow study procedures Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug Females with child bearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug Have an estimated life expectancy of greater than or equal to 12 weeks Are able to swallow capsules Exclusion Criteria: Have received treatment within 3 weeks of the initial dose of study drug with a drug that has not received regulatory approval for any indication Have 1 or more 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, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastasis is not required Have hematologic malignancies, or lymphoma Females who are pregnant or lactating Have a second primary malignancy that, in the judgement of the investigator and sponsor, may affect the interpretation of results Have bleeding diathesis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2584702<br>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. | Drug: LY2584702<br>* administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD) | 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. | Parts A and B, Baseline through Cycle 1 (1 cycle=28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Cmax results on Day 1 and on Day 8 (steady state) are reported. | Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, 8 hours postdose) | 
| Number of Participants With Tumor Response | 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). | Parts A and B, Baseline through study completion [up to Cycle 10 (1 cycle=28 days)] | 
| Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | 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. | Part A, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose) | 
| Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | 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. | Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced cancer