A Study of LY2940680 in Small Cell Lung Cancer

Small Cell Lung Carcinoma Clinical Trial

Official title:

A Phase 1b/2 Double-Blind Randomized Trial of the Hedgehog/SMO Antagonist LY2940680 in Combination With Carboplatin and Etoposide Followed by LY2940680 Versus Carboplatin and Etoposide Plus Placebo Followed by Placebo in Patients With Extensive-Stage Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01722292
• Other study ID #: 14631
• Secondary ID: I4J-MC-HHBE2012-
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 2013
• Est. completion date: February 2015

Study information

• Verified date: September 2015
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• LY2940680
Administered orally
• Carboplatin
Administered IV
• Etoposide
Administered IV
• Placebo
Administered orally

Locations

Country	Name	City	State
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.	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 States	New York Oncology Hematology Associate	Albany	New York
United States	Northeast Georgia Cancer Care, LLC	Athens	Georgia
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Clinical Research Unit (ITOR) Greenville Hospital System	Greenville	South Carolina
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Accelerated Comm. Oncology Research Network (ACORN)	Memphis	Tennessee
United States	The West Clinic	Memphis	Tennessee
United States	Mount Sinai Medical Center	New York	New York
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

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD)	MTD was defined as the highest tested dose that has <33% probability of causing a dose-limiting toxicity(DLT). DLT was defined as an AE during Cycle 1 that is possibly related to the study drug and fulfills any one of the following criterion using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE),version 4.0:Grade 3 non-hematological toxicity except nausea, vomiting, constipation, diarrhea, fatigue, or anorexia that is manageable with appropriate care,transient(i.e., =5 days) Grade 3 elevations of alanine aminotransferase(ALT) and/or aspartate aminotransferase(AST), without evidence of other hepatic injury, in the setting of preexisting hepatic metastasis, =Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia of any duration,CTCAE Grade 4 hematological toxicity of >5 days duration and any febrile neutropenia. any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose-limiting.	Baseline to Completion of the Phase 1b (Up To 12 Months)
Primary	Phase 2: Progression-Free Survival		Randomization to Measured Progressive Disease or Death of Any Cause (Estimated as 18 Months)
Secondary	Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose		Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Secondary	Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose		Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Secondary	Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC0-24) for LY2940680 and LSN3185556 at the Recommended Dose		Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Secondary	Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC0-24) for Etoposide and as AUC0-6 for Carboplatin at the Recommended Dose		Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Secondary	Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])	ORR was defined as the percentage of all randomized participants with the best overall response of PR or CR using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.	Baseline to Study Completion Up to 39 Months
Secondary	Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells	The gene expression data (Gli1) was normalized and the level of percentage of Gli1 inhibition post treatment was calculated.	Baseline, Cycle 2 Day 1, Cycle 7 Day 1
Secondary	Phase 2: Overall Survival		Randomization to Study Completion (Estimated as 38 Months)
Secondary	Phase 2: Percent Change in Tumor Size (CTS)		Randomization to End of Cycle 2 (Estimated as 24 Months)
Secondary	Phase 2: Number of Participants With a Complete or Partial Tumor Response (Overall Response Rate)		Randomization to Study Completion (Estimated as 38 Months)
Secondary	Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose		Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Secondary	Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose		Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours