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| ID | Type | Description | Link |
|---|---|---|---|
| I3O-MC-JSBA | Other Identifier | Eli Lilly and Company |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY2801653 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2801653 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Recommended dose for phase 2 studies: Maximum tolerated dose | Baseline to study completion (estimated as 3 months) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arizona Cancer Center | Tucson | Arizona | 85724 | United States | ||
| Georgetown University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30833489 | Derived | 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. | |
| 23275061 |
| Label | URL |
|---|---|
| Click here for more information about this study:A Study of LY2801653 in Participants With Advanced Cancer | View source |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C586252 | merestinib |
| D000068818 | Cetuximab |
| D002945 | Cisplatin |
| D000093542 | Gemcitabine |
| D000096662 | Ramucirumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Cetuximab | Drug | 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 | Drug | 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 | Drug | 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 | Drug | 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. |
|
|
| 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) |
| Washington D.C. |
| District of Columbia |
| 20007 |
| United States |
| Mount Sinai Medical Center | New York | New York | 10029 | United States |
| University of Pennsylvania Hospital | Philadelphia | Pennsylvania | 19104 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| 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. |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |