A Study of LY2801653 in Advanced Cancer
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01285037 |
|
Recruitment Status :
Completed
First Posted : January 27, 2011
Last Update Posted : February 20, 2018
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
| Study Type : | Interventional (Clinical Trial) |
| 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 : | September 9, 2009 |
| Actual Primary Completion Date : | July 21, 2017 |
| Actual Study Completion Date : | September 11, 2017 |
| 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:
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:
|
- Recommended dose for phase 2 studies: Maximum tolerated dose [ Time Frame: Baseline to study completion (estimated as 3 months) ]
- Number of participants with tumor response [ Time Frame: Part A: Baseline to study completion (estimated as 3 months) ]
- Clinical benefit rate (CBR) [ Time Frame: Parts B, C, D: Baseline to study completion (estimated as 3 months) ]
- Progression free survival (PFS) [ Time Frame: Parts B, C, D: Baseline to study completion (estimated as up to 6 months) ]
- Duration of response [ Time Frame: Parts B, C, D: Baseline to study completion (estimated as up to 6 months) ]
- Number of participants with clinically significant effects [ Time Frame: Baseline to study completion (estimated as 3 months) ]
- Pharmacokinetics: Area under the concentration/time curve (AUC) [ Time Frame: Cycle 1, Day 1; Cycle 2, Day 1 ]
- Pharmacokinetics: Maximum plasma concentration (Cmax) [ Time Frame: Cycle 1, Day 1; Cycle 2, Day 1 ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01285037
| United States, Arizona | |
| Arizona Cancer Center | |
| Tucson, Arizona, United States, 85724 | |
| United States, District of Columbia | |
| Georgetown University Medical Center | |
| Washington, District of Columbia, United States, 20007 | |
| United States, New York | |
| Mount Sinai Medical Center | |
| New York, New York, United States, 10029 | |
| United States, Pennsylvania | |
| University of Pennsylvania Hospital | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Thomas Jefferson University | |
| Philadelphia, Pennsylvania, United States, 19107 | |
| Fox Chase Cancer Center | |
| Philadelphia, Pennsylvania, United States, 19111 | |
| United States, Rhode Island | |
| Rhode Island Hospital | |
| Providence, Rhode Island, United States, 02903 | |
| 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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT01285037 |
| Other Study ID Numbers: |
13008 I3O-MC-JSBA ( Other Identifier: Eli Lilly and Company ) |
| First Posted: | January 27, 2011 Key Record Dates |
| Last Update Posted: | February 20, 2018 |
| Last Verified: | February 2018 |
|
Gemcitabine Cetuximab Ramucirumab Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action |
Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Immunological |