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A Study in Advanced Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01226485
Recruitment Status : Completed
First Posted : October 22, 2010
Results First Posted : September 13, 2019
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The purpose of this study is to find a recommended dose level and schedule of dosing LY2940680 that can safely be taken by participants with advanced cancer. The study will also explore the changes in a cancer marker level in skin, hair follicles, buccal cells, and tumor cells. Finally, the study will help document any antitumor activity this drug may have.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: Taladegib Phase 1

Detailed Description:
Participants may include those who have previously received treatment with another hedgehog smoothened (Hh/Smo) inhibitor (excluding LY2940680).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study of LY2940680 in Patients With Advanced Cancer
Study Start Date : September 2010
Actual Primary Completion Date : January 2015
Actual Study Completion Date : October 2017

Arm Intervention/treatment
Experimental: Taladegib

Part A Cohort 1: 50 milligram (mg) taladegib administered orally QD on a 28-day cycle.

Part A Cohort 2: 100 mg taladegib administered orally QD on a 28-day cycle.

Part A Cohort 3: 200 mg taladegib administered orally QD on a 28-day cycle.

Part A Cohort 4: 400 mg taladegib administered orally QD on a 28-day cycle.

Part A Cohort 5: 600 mg taladegib administered orally QD on a 28-day cycle.

Part C: 400 mg taladegib administered orally QD. Participants with advanced solid tumors.

Part D: 400 mg taladegib administered orally QD. Participants with advanced basal cell carcinoma (BCC).

Drug: Taladegib
Administered IV
Other Name: LY2940680




Primary Outcome Measures :
  1. Recommended Phase 2 Dose: Maximum Tolerated Dose [ Time Frame: Time to First Dose to the End of Cycle 1 of Part A (Up To 28 Days) ]
    Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which was determined by Dose-limiting toxicity (DLT). For the purpose of this study, the MTD was defined as the highest tested dose that had <33% probability of causing a DLT in Cycle 1 of Part A.


Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) [ Time Frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h ]
    Pharmacokinetics (PK): 1.Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞])

  2. PK: Maximum Observed Drug Concentration (Cmax) [ Time Frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h ]
    PK: Maximum Observed Drug Concentration (Cmax)

  3. PK: Time of Maximal Concentration (Tmax) [ Time Frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h ]
    PK: Time of Maximal Concentration (Tmax)

  4. PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 [ Time Frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h ]
    PK: Area Under the Plasma Concentration-time Curve from time Zero to 24 Hours (AUC[0-24]) of LSN3185556

  5. PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 [ Time Frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h ]
    PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556

  6. PK: Time of Maximal Concentration (Tmax) of LSN3185556 [ Time Frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h ]
    PK: Time of Maximal Concentration (Tmax)

  7. Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) [ Time Frame: Baseline to Disease Progression or Death Due to Any Cause (Up To 32 Months) ]
    Clinical Benefit Rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is a ≥20% increase in the sum of diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 millimeter (mm), the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions.

  8. Part C and D: Progression Free Survival (PFS) [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Up To 32 Months) ]
    For each participant in Part C and D who is not known to have died or to have had a progression of disease as of the data inclusion cut-off date, PFS was censored at the date of last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. Progressive disease (PD) was determined using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy.
  • Have the presence of measurable or nonmeasurable disease
  • Have adequate organ function, including:

    • Hematologic: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, platelets greater than or equal to 100 x 109/L, and hemoglobin greater than or equal to 9 g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin until 5 days after the erythrocyte transfusion.
    • Hepatic: Bilirubin less than or equal to 1.5 times upper limits of normal (ULN), ALT, and aspartate transferase (AST) less than or equal to 2.0 times ULN. If the liver has tumor involvement AST and ALT equaling less than or equal to 5 times ULN are acceptable.
    • Renal: Serum creatinine less than or equal to 1.5 times ULN.
  • Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Have discontinued previous treatments for cancer and recovered from the acute effects of therapy (for example, at least 42 days for mitomycin-C or nitrosoureas, 28 days for other chemotherapy and biologics. At the discretion of the investigator, hormone refractory prostate cancer patients who are stable on gonadotropin-releasing hormone (GnRH) agonist therapy and breast cancer patients who are stable on antiestrogen therapy (for example, an aromatase inhibitor) may continue treatment

Exclusion Criteria:

  • Have received treatment within 21 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication.
  • Have serious preexisting medical conditions
  • Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required). Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days.
  • Have known current hematologic malignancies or acute or chronic leukemia
  • Have a known active fungal, bacterial, and/or known viral infection including human immunodeficiency (HIV) or viral (A, B, or C) hepatitis (screening is not required)
  • Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results
  • Have QTc interval of >500 msec on screening electrocardiogram
  • Patients who have previously received treatment with LY2940680

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): NCT01226485


Locations
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United States, Arizona
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.
Scottsdale, Arizona, United States, 85260
United States, California
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.
Redwood City, California, United States, 94063
United States, Colorado
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.
Aurora, Colorado, United States, 80045
United States, Florida
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.
Fort Myers, Florida, United States, 33908
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.
Tampa, Florida, United States, 33612
United States, Nevada
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.
Las Vegas, Nevada, United States, 89169
United States, New York
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.
New York, New York, United States, 10065
United States, Oklahoma
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.
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
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.
Nashville, Tennessee, United States, 37203
United States, Texas
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.
Fort Worth, Texas, United States, 76177
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.
Houston, Texas, United States, 77030
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.
Tyler, Texas, United States, 75702
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01226485    
Other Study ID Numbers: Lilly 13200
I4J-MC-HHBB ( Other Identifier: Eli Lilly and Company )
First Posted: October 22, 2010    Key Record Dates
Results First Posted: September 13, 2019
Last Update Posted: September 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
Cancer
Terminal
Solid Tumor
End Stage
Metastatic
Additional relevant MeSH terms:
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Neoplasms