Clinical trial NCT01722292: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Small Cell Lung Carcinoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-11-06
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD)
timeFrame: Baseline to Completion of the Phase 1b (Up To 12 Months)
measure: Phase 2: Progression-Free Survival
timeFrame: Randomization to Measured Progressive Disease or Death of Any Cause (Estimated as 18 Months)
Secondary outcomes:
measure: Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose
timeFrame: 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
measure: Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose
timeFrame: 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
measure: Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose
timeFrame: 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
measure: Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose
timeFrame: 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
measure: Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
timeFrame: Baseline to Study Completion Up to 39 Months
measure: Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells
timeFrame: Baseline, Cycle 2 Day 1, Cycle 7 Day 1
measure: Phase 2: Overall Survival
timeFrame: Randomization to Study Completion (Estimated as 38 Months)
measure: Phase 2: Percent Change in Tumor Size (CTS)
timeFrame: Randomization to End of Cycle 2 (Estimated as 24 Months)
measure: Phase 2: Number of Participants With a Complete or Partial Tumor Response (Overall Response Rate)
timeFrame: Randomization to Study Completion (Estimated as 38 Months)
measure: Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose
timeFrame: 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
measure: Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose
timeFrame: 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
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Athens
country: United States
facility: Northeast Georgia Cancer Care, LLC
state: Georgia
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology Associate
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Greenville
country: United States
facility: Clinical Research Unit (ITOR) Greenville Hospital System
state: South Carolina
city: Memphis
country: United States
facility: Accelerated Comm. Oncology Research Network (ACORN)
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: The Woodlands
country: United States
facility: US Oncology
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Vancouver
country: United States
facility: Northwest Cancer Specialists PC
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital
state: Washington
city: London
country: United Kingdom
facility: 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: Manchester
country: United Kingdom
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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
References: