A Study of LY2228820 in Participants With Advanced Cancer

Lilly

Status and phase: Completed; Phase 1

Conditions: Advanced Cancer

Treatments: Drug: Midazolam; Drug: Tamoxifen; Drug: LY2228820

Study type: Interventional

Funder types: Industry

Identifiers

NCT01393990

12284

I1D-MC-JIAD (Other Identifier)

Details and patient eligibility

About

The objective of this study is to determine a safe dose of LY2228820 that may be given to participants with advanced cancer. Part A of this study will consist of dose escalation, and Part B will consist of dose confirmation.

Enrollment: 89 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have histological or cytological evidence of a diagnosis of cancer (including lymphoma) that is advanced or metastatic disease for which no therapy of higher priority (approved therapies or therapies with published substantial evidence of effectiveness) is available, or for whom no standard therapy exists
• Have the presence of measurable or nonmeasurable disease as defined by Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
• 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, or other investigational therapy for at least 14 days (42 days for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy
• 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 ≥ 12 weeks
• Are able to swallow capsules and/or tablets

Exclusion criteria

• Have received treatment within 14 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication
• Have a history of major surgical resection involving the stomach or small bowel, or have serious preexisting medical conditions (based on judgment of the investigator)
• Have symptomatic central nervous system malignancy or metastasis (screening is not required)
• Have a diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
• Have an active hematologic malignancy other than lymphoma
• Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). Screening at baseline will not be required for enrollment
• Concurrent administration of any immunosuppressive therapy
• Females who are pregnant or lactating
• Have received, within 7 days of the initial dose of study drug, either grapefruit juice or treatment with a drug that is a known inhibitor or inducer of Cytochrome P450 Enzyme 3A4 (CYP3A4). In addition, participants should not receive grapefruit juice or treatment with a CYP3A4 inhibitor or inducer during the study

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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89 participants in 1 patient group

LY2228820

Experimental group

Description:

The study had 4 parts, dose-escalation (Part A), 2 dose-confirmation (Parts B and C), and a tumor-specific expansion for metastatic breast cancer (Part D). Part A: Participants received escalating doses of 10, 20, 40, 65, 90, 120, 160, 200, 300, 420 and 560 milligrams (mg) of LY2228820 every 12 hours on Days 1 through 14 of a 28-day cycle. Part B: Participants received 420 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Participants received midazolam orally 2 days before the first dose and again after the morning dose of study drug on Day 8 during the first cycle of treatment. Part C: Participants received 300 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Part D: Participants received 200 mg and 300 mg of LY2228820 in combination with tamoxifen.

Treatment:

Drug: Tamoxifen

Drug: LY2228820

Drug: Midazolam