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A Study of LY2940680 in Small Cell Lung Cancer

Primary Purpose

Small Cell Lung Carcinoma

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

LY2940680

Carboplatin

Etoposide

Placebo

About this trial

This is an interventional treatment trial for Small Cell Lung Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Highlands Oncology Group
Northeast Georgia Cancer Care, LLC
Comprehensive Cancer Centers of Nevada
New York Oncology Hematology Associate
Mount Sinai Medical Center
Clinical Research Unit (ITOR) Greenville Hospital System
Accelerated Comm. Oncology Research Network (ACORN)
The West Clinic
US Oncology
Tyler Cancer Center
Northwest Cancer Specialists PC
Yakima Valley Memorial Hospital
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Phase 1b: LY2940680 + C + E

Phase 2: Placebo + C + E

Phase 2: LY2940680 + C+ E

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Phase 2: Progression-Free Survival

Secondary Outcome Measures

Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose

Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose

Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose

Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose

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.

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.

Phase 2: Overall Survival

Phase 2: Percent Change in Tumor Size (CTS)

Phase 2: Number of Participants With a Complete or Partial Tumor Response (Overall Response Rate)

Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose

Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose

Full Information

NCT ID

NCT01722292

First Posted

November 2, 2012

Last Updated

December 6, 2018

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01722292

Brief Title

A Study of LY2940680 in Small Cell Lung Cancer

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Terminated

Why Stopped

Change in clinical strategy.

Study Start Date

January 2013 (undefined)

Primary Completion Date

February 2015 (Actual)

Study Completion Date

February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Small Cell Lung Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1b: LY2940680 + C + E

Arm Type

Experimental

Arm Description

Arm Title

Phase 2: Placebo + C + E

Arm Type

Placebo Comparator

Arm Description

Arm Title

Phase 2: LY2940680 + C+ E

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

LY2940680

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

Administered IV

Intervention Type

Drug

Intervention Name(s)

Etoposide

Intervention Description

Administered IV

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered orally

Primary Outcome Measure Information:

Title

Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD)

Description

Time Frame

Baseline to Completion of the Phase 1b (Up To 12 Months)

Title

Phase 2: Progression-Free Survival

Time Frame

Randomization to Measured Progressive Disease or Death of Any Cause (Estimated as 18 Months)

Secondary Outcome Measure Information:

Title

Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose

Time Frame

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

Title

Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose

Time Frame

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

Title

Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose

Time Frame

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

Title

Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose

Time Frame

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

Title

Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])

Description

Time Frame

Baseline to Study Completion Up to 39 Months

Title

Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells

Description

The gene expression data (Gli1) was normalized and the level of percentage of Gli1 inhibition post treatment was calculated.

Time Frame

Baseline, Cycle 2 Day 1, Cycle 7 Day 1

Title

Phase 2: Overall Survival

Time Frame

Randomization to Study Completion (Estimated as 38 Months)

Title

Phase 2: Percent Change in Tumor Size (CTS)

Time Frame

Randomization to End of Cycle 2 (Estimated as 24 Months)

Title

Phase 2: Number of Participants With a Complete or Partial Tumor Response (Overall Response Rate)

Time Frame

Randomization to Study Completion (Estimated as 38 Months)

Title

Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose

Time Frame

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

Title

Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

Highlands Oncology Group

City

Fayetteville

State/Province

Arkansas

ZIP/Postal Code

72703

Country

United States

Facility Name

Northeast Georgia Cancer Care, LLC

City

Athens

State/Province

Georgia

ZIP/Postal Code

30607

Country

United States

Facility Name

Comprehensive Cancer Centers of Nevada

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89169

Country

United States

Facility Name

New York Oncology Hematology Associate

City

Albany

State/Province

New York

ZIP/Postal Code

12206

Country

United States

Facility Name

Mount Sinai Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Clinical Research Unit (ITOR) Greenville Hospital System

City

Greenville

State/Province

South Carolina

ZIP/Postal Code

29605

Country

United States

Facility Name

Accelerated Comm. Oncology Research Network (ACORN)

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38119

Country

United States

Facility Name

The West Clinic

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38120

Country

United States

Facility Name

US Oncology

City

The Woodlands

State/Province

Texas

ZIP/Postal Code

77380

Country

United States

Facility Name

Tyler Cancer Center

City

Tyler

State/Province

Texas

ZIP/Postal Code

75702

Country

United States

Facility Name

Northwest Cancer Specialists PC

City

Vancouver

State/Province

Washington

ZIP/Postal Code

98684

Country

United States

Facility Name

Yakima Valley Memorial Hospital

City

Yakima

State/Province

Washington

ZIP/Postal Code

98902

Country

United States

Facility Name

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.

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

City

Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com. This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

Learn more about this trial

A Study of LY2940680 in Small Cell Lung Cancer

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