A Study in Advanced Cancer

Phase 1

Completed

Conditions: Advanced Cancer

Interventions: Drug: Taladegib

Registration Number: NCT01226485

Lead Sponsor: 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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 84

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Taladegib	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).

Primary Outcome Measures

Name	Time	Method
Recommended Phase 2 Dose: Maximum Tolerated Dose	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

Name	Time	Method
PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556	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
PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556	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
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞])	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\[0-∞\])
PK: Time of Maximal Concentration (Tmax)	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)
PK: Maximum Observed Drug Concentration (Cmax)	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)
Part C and D: Progression Free Survival (PFS)	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.
PK: Time of Maximal Concentration (Tmax) of LSN3185556	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)
Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR])	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.

Trial Locations

Locations (1): 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.
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Tyler, Texas, United States