Clinical trial NCT01115790: A Phase 1 Study in Participants With Advanced Cancer
Official title: A Phase 1 Study of LY2606368 in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Squamous Cell Carcinoma
Carcinoma, Squamous Cell of Head and Neck
Lung Squamous Cell Carcinoma Stage IV
Anal Squamous Cell Carcinoma
Carcinoma, Non-Small-Cell Lung
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-05-04
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of Parts A and B of this study is to evaluate the safety and toxicity of prexasertib (an inhibitor of checkpoint kinase 1\[chk 1\]) in participants with advanced or metastatic cancer (Part A), or squamous cell cancer of the head and neck or squamous cell cancer of any tumor type (Part B). Part C of the study will evaluate prexasertib in three different groups of participants; those with squamous cell cancer of the head and neck that has recurred or spread to other parts of the body, those with squamous non-small cell lung cancer that has recurred or spread, and those with squamous cell cancer of the anus that is not curable by existing therapy.

Detailed description: Part C added per protocol amendment (February, 2013).

Eligibility criteria: Inclusion Criteria:

* Must be appropriate candidate for experimental therapy, as determined by investigator, after available standard therapies have failed
* Have adequate organ function
* Prior Therapies: Systemic treatments: must have discontinued previous systemic treatments for cancer and recovered from the acute effects of therapy. Participants must have discontinued mitomycin-C or nitrosourea therapy at least 42 days and have discontinued any cytotoxic therapies at least 28 days prior to study enrollment. Radiation therapy and surgery: must be completed at least 4 weeks before study enrollment
* Part A: Must have diagnosis of cancer that is advanced or metastatic
* Part B: Must have histologically confirmed squamous cell cancer of the head and neck or must have squamous cell cancer of any tumor type
* Part C: Must have histological diagnosis of squamous cell cancer of the head and neck, histological or cytological diagnosis of squamous non-small-cell lung cancer, or histological diagnosis of Stage IIIB (N2 or N3) or Stage IV squamous cell cancer of the anus that is not curable by local therapy
* Must be available during the duration of the study and willing to follow the study procedures
* If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for three months following the last dose of study drug
* If the participant is a female of childbearing potential, must have had a negative serum or urine pregnancy test within 7 days of the first dose of study drug and must not be breast feeding

Exclusion Criteria:

* Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment
* Must not have an active symptomatic fungal, bacterial or viral infection, including human immunodeficiency virus (HIV) or Hepatitis A, B, or C
* Must not have a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months
* Must not have systolic blood pressure \<90 millimeters of mercury (mmHg) or recurrent symptomatic orthostatic hypotension
* Must not have a family history of long QTc syndrome or be taking drugs known to cause QTc prolongation or Torsades de Pointes
* Must not have a serotonin-secreting carcinoid tumor or a prior history of drug-induced serotonin syndrome
* Must not have acute leukemia

Primary outcomes:
measure: Determination of a Recommended Phase 2 Dosing Regimen: Maximum Tolerated Dose (Parts A and B)
timeFrame: Time of first dose until last dose (estimated as up to 156 weeks)
measure: Determination of Clinically Significant Safety Effects (Parts A and B)
timeFrame: Time of first dose until last dose (estimated as up to 156 weeks)
measure: Percentage of Participants With a Complete or Partial Response (Overall Response Rate) (Part C)
timeFrame: Baseline until disease progression or death from any cause (estimated as up to 24 weeks)
Secondary outcomes:
measure: Percentage of Participants with Complete Response, Partial Response, or Stable Disease (Disease Control Rate) (Parts A, B, and C)
timeFrame: Baseline until disease progression or death from any cause (estimated as up to 24 weeks)
measure: Progression Free Survival (Parts B and C)
timeFrame: Baseline to measured progressive disease (estimated up to 24 weeks)
measure: Duration of Response (Parts B and C)
timeFrame: First observation of complete response (CR), partial response (PR), or stable disease (SD) to first observation of progressive disease or death (estimated up to 24 weeks)
measure: Preliminary Pharmacokinetics of Prexasertib (Cmax) (Parts A, B, and C)
timeFrame: During Cycles 1 and 2
measure: Preliminary Pharmacokinetics of Prexasertib (AUC) (Parts A, B, and C)
timeFrame: During Cycles 1 and 2
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Oklahoma City
country: United States
facility: Peggy and Charles Stephenson Oklahoma Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute SCRI
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Hong DS, Moore K, Patel M, Grant SC, Burris HA 3rd, William WN Jr, Jones S, Meric-Bernstam F, Infante J, Golden L, Zhang W, Martinez R, Wijayawardana S, Beckmann R, Lin AB, Eng C, Bendell J. Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma. Clin Cancer Res. 2018 Jul 15;24(14):3263-3272. doi: 10.1158/1078-0432.CCR-17-3347. Epub 2018 Apr 11.
citation: Hong D, Infante J, Janku F, Jones S, Nguyen LM, Burris H, Naing A, Bauer TM, Piha-Paul S, Johnson FM, Kurzrock R, Golden L, Hynes S, Lin J, Lin AB, Bendell J. Phase I Study of LY2606368, a Checkpoint Kinase 1 Inhibitor, in Patients With Advanced Cancer. J Clin Oncol. 2016 May 20;34(15):1764-71. doi: 10.1200/JCO.2015.64.5788. Epub 2016 Apr 4.