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A Study of LY2940680 in Small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01722292
First received: November 2, 2012
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Small Cell Lung Carcinoma
Drug: LY2940680
Drug: Carboplatin
Drug: Etoposide
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Phase 1b: Recommended Phase 2 Dose of LY2940680 [ Time Frame: Baseline to Completion of the Phase 1b Portion (Estimated as 9 Months) ] [ Designated as safety issue: No ]
  • Phase 2: Progression-Free Survival [ Time Frame: Randomization to Measured Progressive Disease or Death of Any Cause (Estimated as 18 Months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase 1b and 2: Pharmacokinetics: Maximum Concentration (Cmax) of LY2940680, LSN2941091, carboplatin, and etoposide at the Recommended Dose [ Time Frame: Predose up to 24 Hours Postdose ] [ Designated as safety issue: No ]
  • Phase 1b and 2: Pharmacokinetics: Area Under the Curve (AUC) of LY2940680, LSN2941091, carboplatin, and etoposide at the Recommended Dose [ Time Frame: Predose up to 24 Hours Postdose ] [ Designated as safety issue: No ]
  • Phase 1b: Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate) [ Time Frame: Baseline to Study Completion (Estimated as 38 Months) ] [ Designated as safety issue: No ]
  • Phase 1b: Expression Levels of Gli1 in Skin Cells at the Recommended Dose [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 7 Day 1 ] [ Designated as safety issue: No ]
  • Phase 2: Overall Survival [ Time Frame: Randomization to Study Completion (Estimated as 38 Months) ] [ Designated as safety issue: No ]
  • Phase 2: Percent Change in Tumor Size (CTS) [ Time Frame: Randomization to End of Cycle 2 (Estimated as 24 Months) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680, LSN2941091, carboplatin, and etoposide at the Recommended Dose [ Time Frame: Predose up to 24 Hours Postdose ] [ Designated as safety issue: No ]

Estimated Enrollment: 138
Study Start Date: January 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: LY2940680
Administered orally
Drug: Carboplatin
Administered IV
Drug: Etoposide
Administered IV
Placebo Comparator: 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.

Drug: Carboplatin
Administered IV
Drug: Etoposide
Administered IV
Drug: Placebo
Administered orally
Experimental: 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.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01722292

Contacts
Contact: : There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

  Show 43 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01722292     History of Changes
Other Study ID Numbers: 14631, I4J-MC-HHBE, 2012-003174-83
Study First Received: November 2, 2012
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Small Cell Lung Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide
Etoposide phosphate
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014