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Trial record 50 of 109 for:    hedgehog

A Study of LY2940680 in Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01722292
Recruitment Status : Terminated (Change in clinical strategy.)
First Posted : November 6, 2012
Results First Posted : December 28, 2018
Last Update Posted : December 28, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Small Cell Lung Carcinoma Drug: LY2940680 Drug: Carboplatin Drug: Etoposide Drug: Placebo Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : January 2013
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD) [ Time Frame: Baseline to Completion of the Phase 1b (Up To 12 Months) ]
    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.

  2. Phase 2: Progression-Free Survival [ Time Frame: Randomization to Measured Progressive Disease or Death of Any Cause (Estimated as 18 Months) ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) [ Time Frame: Baseline to Study Completion Up to 39 Months ]
    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.

  6. Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 7 Day 1 ]
    The gene expression data (Gli1) was normalized and the level of percentage of Gli1 inhibition post treatment was calculated.

  7. Phase 2: Overall Survival [ Time Frame: Randomization to Study Completion (Estimated as 38 Months) ]
  8. Phase 2: Percent Change in Tumor Size (CTS) [ Time Frame: Randomization to End of Cycle 2 (Estimated as 24 Months) ]
  9. 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) ]
  10. 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 ]
  11. 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 ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01722292


Locations
United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72703
United States, Georgia
Northeast Georgia Cancer Care, LLC
Athens, Georgia, United States, 30607
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
New York Oncology Hematology Associate
Albany, New York, United States, 12206
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, South Carolina
Clinical Research Unit (ITOR) Greenville Hospital System
Greenville, South Carolina, United States, 29605
United States, Tennessee
Accelerated Comm. Oncology Research Network (ACORN)
Memphis, Tennessee, United States, 38119
The West Clinic
Memphis, Tennessee, United States, 38120
United States, Texas
US Oncology
The Woodlands, Texas, United States, 77380
Tyler Cancer Center
Tyler, Texas, United States, 75702
United States, Washington
Northwest Cancer Specialists PC
Vancouver, Washington, United States, 98684
Yakima Valley Memorial Hospital
Yakima, Washington, United States, 98902
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, SE1 9RT
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 Kingdom, M20 4BX
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

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01722292     History of Changes
Other Study ID Numbers: 14631
I4J-MC-HHBE ( Other Identifier: Eli Lilly and Company )
2012-003174-83 ( EudraCT Number )
First Posted: November 6, 2012    Key Record Dates
Results First Posted: December 28, 2018
Last Update Posted: December 28, 2018
Last Verified: September 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.


Additional relevant MeSH terms:
Small Cell Lung Carcinoma
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Etoposide phosphate
Carboplatin
Etoposide
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action