A Study of LY2801653 in Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01285037
First received: January 26, 2011
Last updated: May 14, 2015
Last verified: May 2015
  Purpose

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 Intervention Phase
Cancer
Drug: LY2801653
Drug: Cetuximab
Drug: Cisplatin
Drug: Gemcitabine
Drug: Ramucirumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of LY2801653 in Patients With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Recommended dose for phase 2 studies: Maximum tolerated dose [ Time Frame: Baseline to study completion (estimated as 3 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with tumor response [ Time Frame: Part A: Baseline to study completion (estimated as 3 months) ] [ Designated as safety issue: No ]
  • Clinical benefit rate (CBR) [ Time Frame: Parts B, C, D: Baseline to study completion (estimated as 3 months) ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) [ Time Frame: Parts B, C, D: Baseline to study completion (estimated as up to 6 months) ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Parts B, C, D: Baseline to study completion (estimated as up to 6 months) ] [ Designated as safety issue: No ]
  • Number of participants with clinically significant effects [ Time Frame: Baseline to study completion (estimated as 3 months) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: Area under the concentration/time curve (AUC) [ Time Frame: Cycle 1, Day 1; Cycle 2, Day 1 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum plasma concentration (Cmax) [ Time Frame: Cycle 1, Day 1; Cycle 2, Day 1 ] [ Designated as safety issue: No ]
  • Maximum tolerated dose (MTD) of LY2801653 in combination with cetuximab for phase 2 studies in HNSCC [ Time Frame: Baseline to study completion (estimated as 3 months) ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose (MTD) of LY2801653 in combination with cisplatin for phase 2 studies in cholangiocarcinoma [ Time Frame: Baseline to study completion (estimated as 3 months) ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose (MTD) of LY2801653 in combination with gemcitabine plus cisplatin for phase 2 studies in cholangiocarcinoma [ Time Frame: Baseline to study completion (estimated as 3 months) ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose (MTD) of LY2801653 in combination with ramucirumab for phase 2 studies in gastric carcinoma [ Time Frame: Baseline to study completion (estimated as 3 months) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 190
Study Start Date: November 2009
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285037

Contacts
Contact: There may be multiple sites in this clinical trial. (1-877-CTLILLY (1-877-285-4559)) or (1-317-615-4559)

Locations
United States, District of Columbia
Georgetown University Medical Center IRB Recruiting
Washington, District of Columbia, United States, 20007
Contact    202-444-2198      
Principal Investigator: Aiwu He         
United States, New York
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact    212-659-5412      
Principal Investigator: Randall Holcombe         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact    215-214-1676      
Principal Investigator: Elizabeth Plimack         
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact    215-503-5455      
Principal Investigator: Nancy Lewis         
University of Pennsylvania Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact    215-662-4469      
Principal Investigator: Roger Cohen         
United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact    401-444-4538      
Principal Investigator: Kimberly Perez         
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
  More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01285037     History of Changes
Other Study ID Numbers: 13008, I3O-MC-JSBA
Study First Received: January 26, 2011
Last Updated: May 14, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cetuximab
Cisplatin
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015