A Study of LY2334737 in Participants With Cancer That is Advanced and/or Has Spread

NCT01648764 | Completed Phase 1 Results

• 3 other identifiers: 119672008-000807-28I1C-MC-JLBE
• Study Type: interventional
• Target: 73
• Locations: 3 countries
• Sites: 4

Brief Summary

The purpose of this study is to evaluate two different dosing regimens of LY2334737 in participants with cancer that is advanced and/or has spread to other parts of the body. Information about side effects will be collected.

Conditions

Malignant Solid Tumor; Solid Tumor; Metastatic Tumor

Outcome Measures

Primary Outcomes (1)

• Recommended Dose for Phase 2 Studies

  Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). The MTD was the highest dose level at which \<2 out of 6 participants experienced a dose-limiting toxicity (DLT) in Cycle 1. DLT was an adverse event (AE) during Cycle 1 that was likely related to LY2334737 and fulfilled any of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 nonhematological (except nausea/vomiting controlled with treatment); Grade 3 neutropenia with fever or any Grade 4 neutropenia with or without fever; Grade 3 thrombocytopenia with ≥Grade 2 bleeding or Grade 4 thrombocytopenia with or without bleeding; A recovery period longer than 14 days from last dose of LY2334737 to values allowing Cycle 2 to start; Other significant drug-related toxicity deemed by investigator to be dose limiting or that caused the participant to withdraw from the study. Pharmacokinetics and pharmacodynamics (PK/PD) were also taken into consideration for Phase 2 recommended dose.

  Baseline up to 28 days postdose in Cycle 1 (28-day cycle)

Secondary Outcomes (9)

• Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for LY2334737

  Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle

• Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for 2'2'-Difluorodeoxycytidine (dFdC)

  Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours post dose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours post dose of 28-day cycle

• Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for Difluorodeoxyuridine (dFdU)

  Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle

• Pharmacokinetics: Maximum Plasma Concentration (Cmax)

  Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle

• Number of Participants With Best Overall Response (BOR)

  Baseline to measured disease progression up to 33 weeks

Other Outcomes (1)

• Number of Participants With Dose-Limiting Toxicity (DLT)

  Cycle 1 (28-day cycle)

Study Arms (2)

LY2334737 - Arm A

EXPERIMENTAL

LY2334737 administered orally at escalating doses \[40 milligrams (mg) - 200 mg\] every other day for 21 days followed by 7 days without study drug (28 day treatment cycle). Participants may receive additional treatment cycles until discontinuation criterion is met.

Drug: LY2334737

LY2334737 - Arm B

EXPERIMENTAL

LY2334737 administered orally at escalating doses (40 mg - 200 mg) every day for 7 days followed by 7 days without study drug then repeated (28 day treatment cycle). Participants may receive additional treatment cycles until discontinuation criterion is met.

Drug: LY2334737

Interventions

LY2334737 DRUG

Administered orally

LY2334737 - Arm A; LY2334737 - Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of advanced and/or metastatic cancer (including lymphoma) for which no treatment of higher priority exists
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Estimated life expectancy of more than 12 weeks
• Have discontinued all previous therapies for cancer for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) and recovered from acute effects of therapy
• Have discontinued radiotherapy more than one week before enrolling in the study and have recovered from the acute effects of therapy
• Have adequate organ function
• Follow your doctor's directions and live close enough to the study site so you can continue to go to the clinic for follow-up
• Are willing and able to swallow capsules and follow study procedures
• Have given written informed consent prior to any study-specific procedures
• Males and females with reproductive potential should use medically approved contraceptive precautions during the study and for 6 months following the last dose of study drug
• Females with child-bearing potential must have had a negative urine or serum pregnancy test 7 days prior to the first dose of study drug

You may not qualify if:

• Have gastrointestinal diseases or prior surgery that may interfere with the absorption of medication taken by mouth
• Females who are pregnant or lactating
• Symptomatic central nervous system malignancy or metastasis
• Known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb)
• Liver cirrhosis or chronic hepatitis
• Acute or chronic leukemia
• Are currently receiving treatment with valproic acid (VPA) and its derivatives, or if you have a history of intolerance to VPA
• Known hypersensitivity to gemcitabine

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (4)

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.

Philadelphia, Pennsylvania, 19111, United States

Location

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.

Clichy, 92118, France

Location

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.

Berlin, 13353, Germany

Location

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.

Nuremberg, 90419, Germany

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

LY2334737

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2012
• First Posted: July 24, 2012
• Study Start: September 1, 2008
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: June 17, 2019
• Results First Posted: June 17, 2019

Record last verified: 2019-03

Locations

DE (2); US (1); FR (1)