A Dose-Escalation Study for Patients With Advanced Cancer

Study Overview
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Brief Summary
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This study is being conducted to determine the safety of LY2523355 for the treatment of advanced and/or metastatic cancer (including Non-Hodgkin's lymphoma).

Detailed Description
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This study is a multi-center, non-randomized, open label, dose-escalation, Phase 1 study of intravenous LY2523355 in patients with advanced and/or metastatic cancer (including non-Hodgkin's lymphoma) for whom no treatment of higher priority exists.

Official Title
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A Phase 1 Dose-Escalation Study of LY2523355 in Patients With Advanced Cancer

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: pegfilgrastim
* Drug: LY2523355


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of advanced and/or metastatic cancer (solid tumors or Non-Hodgkin's lymphoma) that is refractory to standard therapy or for which no proven effective therapy exists. Participants entering the dose confirmation phase (Part B) of the study must also have a tumor that is safely amenable to serial biopsies Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) or Revised International Working Group Lymphoma Response Criteria Have a performance status of 0 or 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 28 days (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment 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 urine or 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. Exclusion Criteria: Have symptomatic, untreated or uncontrolled central nervous system (CNS) metastases. 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 metastases is not required Have current acute or chronic leukemia Have had an autologous or allogenic bone marrow transplant Females who are pregnant or lactating

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2523355 Days 1, 5, 9<br>LY2523355 administered intravenously on Days 1, 5 and 9, starting dose is 2 milligrams per meter squared (mg/m^2) for 2 planned 21-day cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion are met. | Drug: LY2523355<br>* Administered intravenously<br>|
| Experimental: LY2523355 Days 1, 8<br>LY2523355 administered intravenously on Days 1 and 8, starting dose is 8 mg/m^2 for 2 planned 21-day cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion are met. | Drug: LY2523355<br>* Administered intravenously<br>|
| Experimental: LY2523355 Days 1, 5 + pegfilgrastim<br>LY2523355 administered intravenously on Days 1 and 5, starting dose is 8 mg/m^2 for 2 planned 21-day cycles and 6 mg pegfilgrastim administered subcutaneously on Day 6 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion are met. | Drug: pegfilgrastim<br>* Administered subcutaneously<br>Drug: LY2523355<br>* Administered intravenously<br>|
| Experimental: LY2523355 Days 1, 4 + pegfilgrastim<br>LY2523355 administered on Days 1 and 4, starting dose is 12 mg/m^2 for 2 planned 21-day cycles and 6 mg pegfilgrastim administered subcutaneously on Day 5 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion are met. | Drug: pegfilgrastim<br>* Administered subcutaneously<br>Drug: LY2523355<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Dose and Schedule for Phase 2 Studies | The recommended dose and schedule for Phase 2 studies is defined as the maximum tolerated dose (MTD). MTD is defined as the dose level at which no more than 2 dose limiting toxicities (DLTs), no more than 3 dose reductions (DR) or dose omissions (DO) and no more than 1 DLT plus 2 DR/DO occurred. DLT is defined as an adverse event (AE) occurring in Cycle 1 with the following criteria according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0: Any ≥Grade 3 nonhematological toxicity (except nausea/vomiting or diarrhea controlled with treatment or fatigue); ≥Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding; Grade 4 hematological toxicity of >5 days duration, excluding thrombocytopenia; febrile neutropenia. | Cycle 1 (21 days): Day 1, 5 and 9, any AE reported | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Effects | Clinically significant effects were defined as serious and other non-serious adverse events (AEs). A summary of serious and other non-serious AEs is located in the Reported Adverse Events module. | Baseline to Cycle 38 (21-day cycles): daily for AEs | 
| Pharmacokinetics Maximum Concentration (Cmax), Single Dose | Plasma Cmax following a single dose of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG). | Cycle 1 Day 1 of 21-day cycle: Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose | 
| Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | Plasma Cmax following multiple doses of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG). | Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose | 
| Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | Plasma AUC from time zero to infinity [AUC(0-∞)] and AUC from time zero to 24 hours post-dose [AUC(0-24)] following a single dose of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG). | Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose | 
| Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | Plasma AUC from time zero to infinity (0-∞) and AUC from time zero to 24 hours (0-24) post-dose following multiple doses of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG). | Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose | 
| Number of Participants With Tumor Response | Response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and the Revised International Working Group (IWG) lymphoma response criteria for lymphoma patients. Complete Response (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 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. Tumor response is CR + PR. | Baseline to measured disease progression or discontinuation up to Cycle 38 (21-day cycles) | 

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