A Study of LY2940680 in Small Cell Lung Cancer

NCT01722292 | Terminated Phase 1 Results

• 3 other identifiers: 14631I4J-MC-HHBE2012-003174-83
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 14

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

Outcome Measures

Primary Outcomes (2)

• 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)

• Phase 2: Progression-Free Survival

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

Secondary Outcomes (11)

• 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

• 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

• 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

• 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

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

  Baseline to Study Completion Up to 39 Months

Study Arms (3)

Phase 1b: LY2940680 + C + E

EXPERIMENTAL

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.

Drug: LY2940680; Drug: Carboplatin; Drug: Etoposide

Phase 2: Placebo + C + E

PLACEBO COMPARATOR

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.

Drug: Carboplatin; Drug: Etoposide; Drug: Placebo

Phase 2: LY2940680 + C+ E

EXPERIMENTAL

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.

Drug: LY2940680; Drug: Carboplatin; Drug: Etoposide

Interventions

LY2940680 DRUG

Administered orally

Phase 1b: LY2940680 + C + E; Phase 2: LY2940680 + C+ E

Carboplatin DRUG

Administered IV

Phase 1b: LY2940680 + C + E; Phase 2: LY2940680 + C+ E; Phase 2: Placebo + C + E

Etoposide DRUG

Administered IV

Phase 1b: LY2940680 + C + E; Phase 2: LY2940680 + C+ E; Phase 2: Placebo + C + E

Placebo DRUG

Administered orally

Phase 2: Placebo + C + E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (14)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Northeast Georgia Cancer Care, LLC

Athens, Georgia, 30607, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

New York Oncology Hematology Associate

Albany, New York, 12206, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Clinical Research Unit (ITOR) Greenville Hospital System

Greenville, South Carolina, 29605, United States

Location

Accelerated Comm. Oncology Research Network (ACORN)

Memphis, Tennessee, 38119, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

US Oncology

The Woodlands, Texas, 77380, United States

Location

Tyler Cancer Center

Tyler, Texas, 75702, United States

Location

Northwest Cancer Specialists PC

Vancouver, Washington, 98684, United States

Location

Yakima Valley Memorial Hospital

Yakima, Washington, 98902, United States

Location

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, SE1 9RT, United Kingdom

Location

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, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

LY2940680; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Limitations and Caveats

Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2012
• First Posted: November 6, 2012
• Study Start: January 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: December 28, 2018
• Results First Posted: December 28, 2018

Record last verified: 2015-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (2); US (12)