A Study of LY2801653 in Advanced Cancer

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Completed

CT.gov ID

NCT01285037

Collaborator

(none)

190

Enrollment

Locations

Arm

96.1

Actual Duration (Months)

27.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: LY2801653 Drug: Cetuximab Drug: Cisplatin Drug: Gemcitabine Drug: Ramucirumab	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

190 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of LY2801653 in Patients With Advanced Cancer

Actual Study Start Date :

Sep 9, 2009

Actual Primary Completion Date :

Jul 21, 2017

Actual Study Completion Date :

Sep 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2801653 This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B). Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort. Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort. Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin. Part F consists of dose determination for LY2801653 in combination with ramicirumab.	Drug: LY2801653 LY2801653 given orally once daily during 28-day cycles. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met. Drug: Cetuximab Cetuximab given via IV infusion once weekly, 400mg/m2 for first dose and 250mg /m2 for subsequent doses. If LY2801653 treatment is stopped due to toxicity after a minimum of 4 cycles, cetuximab may be continued until disease progression. In the event cetuximab treatment is stopped, participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met. Drug: Cisplatin Cisplatin given via IV infusion once a week for 2 weeks and then every 3 weeks. If the LY2801653 is terminated for LY2801653-related toxicity after a minimum of 4 cycles, cisplatin may be continued as monotherapy until progression of disease. Participants discontinuing cisplatin therapy may be allowed to continue single agent LY2801653 if they are receiving clinical benefit. Drug: Gemcitabine Gemcitabine given via IV infusion once a week for 2 weeks and then every 3 weeks. If the LY2801653 is terminated for LY2801653-related toxicity after a minimum of 4 cycles, gemcitabine may be continued as monotherapy until progression of disease. Participants discontinuing gemcitabine therapy may be allowed to continue single agent LY2801653 if they are receiving clinical benefit. Other Names: LY188011 Gemzar Drug: Ramucirumab Ramucirumab given via IV infusion every 2 weeks in a 28-day treatment cycle. Treatment with ramucirumab may continue until excessive toxicity or evidence of disease progression. In the absence of disease progression, treatment with LY2801653 may continue even if ramucirumab is discontinued provided no dose limiting toxicity related to LY2801653 is present. In the event that LY2801653 is discontinued, treatment with ramucirumab may be continued if there is no dose limiting toxicity related to ramucirumab. Other Names: IMC-1121B LY3009806 Cyramza

Arm

Intervention/Treatment

Experimental: LY2801653

This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B). Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort. Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort. Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin. Part F consists of dose determination for LY2801653 in combination with ramicirumab.

Drug: LY2801653

LY2801653 given orally once daily during 28-day cycles. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.

Drug: Cetuximab

Cetuximab given via IV infusion once weekly, 400mg/m2 for first dose and 250mg /m2 for subsequent doses. If LY2801653 treatment is stopped due to toxicity after a minimum of 4 cycles, cetuximab may be continued until disease progression. In the event cetuximab treatment is stopped, participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.

Drug: Cisplatin

Cisplatin given via IV infusion once a week for 2 weeks and then every 3 weeks. If the LY2801653 is terminated for LY2801653-related toxicity after a minimum of 4 cycles, cisplatin may be continued as monotherapy until progression of disease. Participants discontinuing cisplatin therapy may be allowed to continue single agent LY2801653 if they are receiving clinical benefit.

Drug: Gemcitabine

Gemcitabine given via IV infusion once a week for 2 weeks and then every 3 weeks. If the LY2801653 is terminated for LY2801653-related toxicity after a minimum of 4 cycles, gemcitabine may be continued as monotherapy until progression of disease. Participants discontinuing gemcitabine therapy may be allowed to continue single agent LY2801653 if they are receiving clinical benefit.

Other Names:

LY188011

Gemzar

Drug: Ramucirumab

Ramucirumab given via IV infusion every 2 weeks in a 28-day treatment cycle. Treatment with ramucirumab may continue until excessive toxicity or evidence of disease progression. In the absence of disease progression, treatment with LY2801653 may continue even if ramucirumab is discontinued provided no dose limiting toxicity related to LY2801653 is present. In the event that LY2801653 is discontinued, treatment with ramucirumab may be continued if there is no dose limiting toxicity related to ramucirumab.

Other Names:

IMC-1121B

LY3009806

Cyramza

Outcome Measures

Primary Outcome Measures

Recommended dose for phase 2 studies: Maximum tolerated dose [Baseline to study completion (estimated as 3 months)]

Secondary Outcome Measures

Number of participants with tumor response [Part A: Baseline to study completion (estimated as 3 months)]
Clinical benefit rate (CBR) [Parts B, C, D: Baseline to study completion (estimated as 3 months)]
Progression free survival (PFS) [Parts B, C, D: Baseline to study completion (estimated as up to 6 months)]
Duration of response [Parts B, C, D: Baseline to study completion (estimated as up to 6 months)]
Number of participants with clinically significant effects [Baseline to study completion (estimated as 3 months)]
Pharmacokinetics: Area under the concentration/time curve (AUC) [Cycle 1, Day 1; Cycle 2, Day 1]
Pharmacokinetics: Maximum plasma concentration (Cmax) [Cycle 1, Day 1; Cycle 2, Day 1]
Maximum tolerated dose (MTD) of LY2801653 in combination with cetuximab for phase 2 studies in HNSCC [Baseline to study completion (estimated as 3 months)]
Maximum tolerated dose (MTD) of LY2801653 in combination with cisplatin for phase 2 studies in cholangiocarcinoma [Baseline to study completion (estimated as 3 months)]
Maximum tolerated dose (MTD) of LY2801653 in combination with gemcitabine plus cisplatin for phase 2 studies in cholangiocarcinoma [Baseline to study completion (estimated as 3 months)]
Maximum tolerated dose (MTD) of LY2801653 in combination with ramucirumab for phase 2 studies in gastric carcinoma [Baseline to study completion (estimated as 3 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center	Tucson	Arizona	United States	85724
2	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
3	Mount Sinai Medical Center	New York	New York	United States	10029
4	University of Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19104
5	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
6	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
7	Rhode Island Hospital	Providence	Rhode Island	United States	02903

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Director: Call 1-877-CTLILLY (1-817-285-4559) or 1-317-615-4559 Mon - Fri 9AM to 5PM Eastern time (UTC/GMT - 5hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Click here for more information about this study:A Study of LY2801653 in Participants With Advanced Cancer

Publications

None provided.

Responsible Party:

Eli Lilly and Company

ClinicalTrials.gov Identifier:

NCT01285037

Other Study ID Numbers:

13008
I3O-MC-JSBA

First Posted:

Jan 27, 2011

Last Update Posted:

Feb 20, 2018

Last Verified:

Feb 1, 2018

Additional relevant MeSH terms:

Gemcitabine

Cetuximab

Ramucirumab

Study Results

No Results Posted as of Feb 20, 2018