Clinical trial NCT01285037: A Study of LY2801653 in Advanced Cancer
Official title: A Phase 1 Study of LY2801653 in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-01-27
Enrollment: 190
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: Part A- The purpose of this study is to determine a safe dose of LY2801653 to be given to participants with advanced cancer and to determine any side effects that may be associated with LY2801653 in this participant population. Efficacy measures will be used to assess the activity of LY2801653.

Part B- The dose determined in Part A will be used along with efficacy measures to assess the activity of LY2801653 in participants with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma (HNSCC), uveal melanoma with liver metastasis, and cholangiocarcinoma.

Part C - the objective of Part C is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with HNSCC when taken with standard doses of cetuximab Part D - the objective of Part D is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with a standard dose of cisplatin.

Part E - the objective of Part E is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with gemcitabine plus cisplatin.

Part F - the objective of Part F is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with gastric cancer when taken with ramucirumab.

Detailed description: Parts C and D were added to the registration in November, 2013, per protocol amendment. Parts E and F were added to the registration in February, 2015, per protocol amendment.

Eligibility criteria: Inclusion Criteria:

* Part A- Diagnosed with advanced and/or metastatic cancer during dose escalation
* Part B- Diagnosed with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver with metastasis, or cholangiocarcinoma
* Part C - Diagnosed with head and neck squamous cell carcinoma and have received at least one prior platinum-based systemic therapy
* Part D - Diagnosed with cholangiocarcinoma and have not received more than 1 prior systemic therapy
* Part E - Diagnosed with cholangiocarcinoma, either intrahepatic or extrahepatic, that is unresectable, recurrent, or metastatic. Participants must not have received prior systemic front line therapy for metastatic or resectable disease (i.e. participants may have received adjuvant gemcitabine but have not yet received gemcitabine/cisplatin for recurrent metastatic disease). Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. Participants should be evaluated for the need to undergo biliary drainage by stent placement prior to study participation. Participants should have adequate biliary drainage with no unresolved biliary obstruction.
* Part F - Histologically- or cytologically-confirmed gastric carcinoma, including gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma (participants with adenocarcinoma of the distal esophagus are eligible if the primary tumor involves the GEJ). Participants must be ramucirumab naïve. Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. human epidermal growth factor receptor 2 (HER2)/neu status should be documented, if known.
* Must be at least 18 years of age
* Adequate hematologic, renal, and liver functions
* Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
* Ability to swallow capsules, with the exception of head and neck squamous cell carcinoma participants who may have study drug crushed and administered through a feeding tube

Exclusion Criteria:

* Have serious preexisting medical conditions that would preclude participation in the study
* Have a chronic underlying infection
* Have symptomatic central nervous system (CNS) malignancy or metastasis
* Have current acute or chronic leukemia
* Are pregnant or lactating
* Have hepatocellular cancer, liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplant
* Have a history of congestive heart failure with a New York Heart Association class greater than 2, unstable angina, recent myocardial infarction (within 6 months of study enrollment), transient ischemic attacks, stroke, or arterial or venous vascular disease
* Have a QTc interval greater than 470 msec
* For participants in Part B, C, D, E, and F, a tumor tissue sample is mandatory, when safe and feasible, for biomarker analysis

Primary outcomes:
measure: Recommended dose for phase 2 studies: Maximum tolerated dose
timeFrame: Baseline to study completion (estimated as 3 months)
Secondary outcomes:
measure: Number of participants with tumor response
timeFrame: Part A: Baseline to study completion (estimated as 3 months)
measure: Clinical benefit rate (CBR)
timeFrame: Parts B, C, D: Baseline to study completion (estimated as 3 months)
measure: Progression free survival (PFS)
timeFrame: Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
measure: Duration of response
timeFrame: Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
measure: Number of participants with clinically significant effects
timeFrame: Baseline to study completion (estimated as 3 months)
measure: Pharmacokinetics: Area under the concentration/time curve (AUC)
timeFrame: Cycle 1, Day 1; Cycle 2, Day 1
measure: Pharmacokinetics: Maximum plasma concentration (Cmax)
timeFrame: Cycle 1, Day 1; Cycle 2, Day 1
measure: Maximum tolerated dose (MTD) of LY2801653 in combination with cetuximab for phase 2 studies in HNSCC
timeFrame: Baseline to study completion (estimated as 3 months)
measure: Maximum tolerated dose (MTD) of LY2801653 in combination with cisplatin for phase 2 studies in cholangiocarcinoma
timeFrame: Baseline to study completion (estimated as 3 months)
measure: Maximum tolerated dose (MTD) of LY2801653 in combination with gemcitabine plus cisplatin for phase 2 studies in cholangiocarcinoma
timeFrame: Baseline to study completion (estimated as 3 months)
measure: Maximum tolerated dose (MTD) of LY2801653 in combination with ramucirumab for phase 2 studies in gastric carcinoma
timeFrame: Baseline to study completion (estimated as 3 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-817-285-4559) or 1-317-615-4559 Mon - Fri 9AM to 5PM Eastern time (UTC/GMT - 5hours, EST)
role: STUDY_DIRECTOR
References:
citation: He AR, Cohen RB, Denlinger CS, Sama A, Birnbaum A, Hwang J, Sato T, Lewis N, Mynderse M, Niland M, Giles J, Wallin J, Moser B, Zhang W, Walgren R, Plimack ER. First-in-Human Phase I Study of Merestinib, an Oral Multikinase Inhibitor, in Patients with Advanced Cancer. Oncologist. 2019 Sep;24(9):e930-e942. doi: 10.1634/theoncologist.2018-0411. Epub 2019 Mar 4.
citation: Yan SB, Peek VL, Ajamie R, Buchanan SG, Graff JR, Heidler SA, Hui YH, Huss KL, Konicek BW, Manro JR, Shih C, Stewart JA, Stewart TR, Stout SL, Uhlik MT, Um SL, Wang Y, Wu W, Yan L, Yang WJ, Zhong B, Walgren RA. LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2013 Aug;31(4):833-44. doi: 10.1007/s10637-012-9912-9. Epub 2012 Dec 29.