A Dose-Escalation Study for Patients With Advanced Cancer

• ClinicalTrials.gov Identifier: NCT01214642
• Recruitment Status: Completed
• First Posted: October 5, 2010
• Results First Posted: August 6, 2018
• Last Update Posted: August 6, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Advanced Cancer	Drug: pegfilgrastim; Drug: LY2523355	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 63 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Dose-Escalation Study of LY2523355 in Patients With Advanced Cancer
• Study Start Date: May 2008
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: June 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: LY2523355 Days 1, 5, 9; 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; Administered intravenously
Experimental: LY2523355 Days 1, 8; 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; Administered intravenously
Experimental: LY2523355 Days 1, 5 + pegfilgrastim; 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; Administered subcutaneously; Drug: LY2523355; Administered intravenously
Experimental: LY2523355 Days 1, 4 + pegfilgrastim; 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; Administered subcutaneously; Drug: LY2523355; Administered intravenously

Outcome Measures

Primary Outcome Measures :

1. Recommended Dose and Schedule for Phase 2 Studies [ Time Frame: Cycle 1 (21 days): Day 1, 5 and 9, any AE reported ]
   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.

Secondary Outcome Measures :

1. Number of Participants With Clinically Significant Effects [ Time Frame: Baseline to Cycle 38 (21-day cycles): daily for AEs ]
   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.
2. Pharmacokinetics Maximum Concentration (Cmax), Single Dose [ Time Frame: Cycle 1 Day 1 of 21-day cycle: Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose ]
   Plasma Cmax following a single dose of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG).
3. Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose [ Time Frame: 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 ]
   Plasma Cmax following multiple doses of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG).
4. Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose [ Time Frame: 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 ]
   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).
5. Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose [ Time Frame: 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 ]
   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).
6. Number of Participants With Tumor Response [ Time Frame: Baseline to measured disease progression or discontinuation up to Cycle 38 (21-day cycles) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Tennessee

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.

Nashville, Tennessee, United States, 37203

United States, Texas

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.

San Antonio, Texas, United States, 78229-3307

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01214642
• Other Study ID Numbers: 11619; I1Y-MC-JFBB ( Other Identifier: Eli Lilly and Company )
• First Posted: October 5, 2010
• Results First Posted: August 6, 2018
• Last Update Posted: August 6, 2018
• Last Verified: August 2018

Keywords provided by Eli Lilly and Company:

Advanced Cancer; Cancer

Additional relevant MeSH terms:

Neoplasms