A Study of LY2940680 in Small Cell Lung Cancer

NCT ID: NCT01722292

Last Updated: 2018-12-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2015-02-28

Brief Summary

The purpose of this study is to find a recommended dose of LY2940680 that can be safely given in combination with etoposide and carboplatin followed by LY2940680 alone in participants with extensive-disease small cell lung cancer. The study will also compare progression-free survival in participants who are administered etoposide, carboplatin and LY2940680 followed by LY2940680 alone versus etoposide, carboplatin, and placebo followed by placebo alone.

Conditions

Small Cell Lung Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Phase 1b: LY2940680 + C + E

Phase 1b Dose Escalation: Cycles 1-6 (21 day cycles) LY2940680 administered orally, once daily at escalating doses (100 milligrams [mg] up to 400 mg) in combination with etoposide (E) 100 milligram per square meter (mg/m^2) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle and carboplatin (C) Area Under the Curve [AUC] 5 (mg•min/mL) administered by IV infusion on day 1 each cycle.

Phase 1b Maintenance: Cycles 7+ (21 day cycles) LY2940680 administered orally, once daily at the same dose as induction. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Group Type: EXPERIMENTAL

LY2940680

Intervention Type: DRUG

Administered orally

Carboplatin

Intervention Type: DRUG

Administered IV

Etoposide

Intervention Type: DRUG

Administered IV

Phase 2: Placebo + C + E

Induction: Cycles 1-6 (21 day cycles) Placebo administered orally once daily in combination with etoposide 100 mg/m2 administered by IV infusion on days 1, 2, 3 of each cycle and carboplatin AUC 5 administered by IV infusion on day 1 each cycle.

Maintenance: Cycles 7+ (21 day cycles) Placebo administered orally once daily. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Group Type: PLACEBO_COMPARATOR

Carboplatin

Intervention Type: DRUG

Administered IV

Etoposide

Intervention Type: DRUG

Administered IV

Placebo

Intervention Type: DRUG

Administered orally

Phase 2: LY2940680 + C+ E

Induction: Cycles 1-6 (21 day cycles) LY2940680 (dose to be determined in Phase 1b portion) administered orally once daily in combination with etoposide 100 mg/m^2 administered by IV infusion on days 1, 2, 3 of each cycle and carboplatin AUC 5 administered by IV infusion on day 1 each cycle.

Maintenance: Cycles 7+ (21 day cycles). LY2940680 (dose to be determined in Phase 1 portion) administered orally once daily.

Group Type: EXPERIMENTAL

LY2940680

Intervention Type: DRUG

Administered orally

Carboplatin

Intervention Type: DRUG

Administered IV

Etoposide

Intervention Type: DRUG

Administered IV

Interventions

LY2940680

Administered orally

Intervention Type: DRUG

Carboplatin

Administered IV

Intervention Type: DRUG

Etoposide

Administered IV

Intervention Type: DRUG

Placebo

Administered orally

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histological or cytological diagnosis of Small Cell Lung Cancer (SCLC), including malignant pleural effusion that is extensive stage per the International Staging System
• Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) performance status schedule
• No prior systemic chemotherapy, immunotherapy, or biological therapy for SCLC
• Prior radiation therapy allowed to <25% of the bone marrow. Participants who have received prior radiation to the whole pelvis or chest for the treatment of SCLC are not eligible
• At least 1 unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Adequate organ function including the following:

• Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥1.5 x 10^9/ liter (L), platelets ≥100 x 10^9/L, and hemoglobin ≥9 grams/deciliter (g/dL)
• Hepatic: bilirubin ≤1.5 times the upper limit of normal (ULN), alkaline phosphatase (AP), Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3.0 x ULN (AP, AST, and ALT ≤5 x ULN is acceptable if liver has tumor involvement)
• Renal: calculated creatinine clearance (CrCl) ≥50 milliliters per minute (mL/min) based on the standard Cockcroft and Gault formula
• Estimated life expectancy of at least 12 weeks
• For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 6 months after the treatment period; must have a negative serum pregnancy test within 7 days before study enrollment. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period
• Availability of a tumor tissue sample
• Able to swallow capsules

Exclusion Criteria

• Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have previously participated in a study involving LY2940680
• Have previously received treatment with carboplatin or etoposide
• Have a mixed histological diagnosis of SCLC and Non-Small Cell Lung Cancer (NSCLC)
• Have a serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol
• Have an active infection [≥38.5 degrees Celsius and/or receiving Intravenous (IV) antibiotic therapy]
• Have a serious cardiac condition
• Have had a prior malignancy other than SCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Participants with a history of non-metastatic prostate cancer, including biochemical relapse only, will be eligible even if diagnosed less than 5 years previously
• Symptomatic central nervous system (CNS) metastases and asymptomatic CNS metastases requiring concurrent corticosteroid therapy. Treated stable CNS metastases are allowed; the participant must be stable after radiotherapy for ≥2 weeks and off of corticosteroids for ≥1 week
• Presence of clinically significant third-space fluid collections that cannot be controlled prior to study entry
• Significant weight loss (that is, ≥10%) over the 6-week period prior to study entry
• Concurrent administration of any other antitumor therapy. An exception will be made for non-metastatic prostate cancer participants continuing androgen blockade therapy only or breast cancer participants continuing adjuvant antiestrogen therapy only (for example, an aromatase inhibitor)
• Females who are breastfeeding
• Have corrected QT interval (QTc) of >470 millisecond (msec) on screening electrocardiogram (ECG)
• Have received medications that are strong inhibitors of Cytochrome P450 3A4 (CYP3A4) within 7 days prior to receiving study drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Highlands Oncology Group

Fayetteville, Arkansas, United States

Northeast Georgia Cancer Care, LLC

Athens, Georgia, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

New York Oncology Hematology Associate

Albany, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Clinical Research Unit (ITOR) Greenville Hospital System

Greenville, South Carolina, United States

Accelerated Comm. Oncology Research Network (ACORN)

Memphis, Tennessee, United States

The West Clinic

Memphis, Tennessee, United States

US Oncology

The Woodlands, Texas, United States

Tyler Cancer Center

Tyler, Texas, United States

Northwest Cancer Specialists PC

Vancouver, Washington, United States

Yakima Valley Memorial Hospital

Yakima, Washington, United States

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.

London, , United Kingdom

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.

Manchester, , United Kingdom

Countries

Belgium; South Korea; United States; United Kingdom

Other Identifiers

I4J-MC-HHBE

Identifier Type: OTHER

Identifier Source: secondary_id

2012-003174-83

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

14631

Identifier Type: -

Identifier Source: org_study_id