A Study of LY2801653 in Advanced Cancer

Cancer Clinical Trial

Official title:

A Phase 1 Study of LY2801653 in Patients With Advanced Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285037
• Other study ID #: 13008
• Secondary ID: I3O-MC-JSBA
• Status: Completed
• Phase: Phase 1
• First received: January 26, 2011
• Last updated: February 19, 2018
• Start date: September 9, 2009
• Est. completion date: September 11, 2017

Study information

• Verified date: February 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: September 11, 2017
• Est. primary completion date: July 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Mount Sinai Medical Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Arizona Cancer Center	Tucson	Arizona
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

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