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| ID | Type | Description | Link |
|---|---|---|---|
| I4D-MC-JTJF | Other Identifier | Eli Lilly and Company |
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The main purpose of this study is to investigate the safety of prexasertib in combination with other anti-cancer drugs (cisplatin, cetuximab, pemetrexed, fluorouracil or LY3023414) in participants with advanced cancer or cancer that has spread to another part of the body. The study has multiple parts (A, B, C, D and E). Participants will only enroll in one part.
The primary purpose of Parts A, B, C, D and E of this study is to determine a recommended dose level and schedule of prexasertib (an inhibitor of checkpoint kinase 1 and 2 [CHK1/CHK2] in combination with:
in participants with advanced or metastatic cancer.
Part A dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with cisplatin in participants with advanced or metastatic cancer, Part B dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with cetuximab in participants with advanced or metastatic colorectal cancer, Part C and D dose expansions have been removed and Part E dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with LY3023414 in participants with advanced or metastatic cancer, participants with PIK3CA mutations, or with advanced or metastatic breast cancer.
In Parts A and B the effect of adding granulocyte colony stimulating factor (G-CSF) to cisplatin in combination with prexasertib and cetuximab in combination with prexasertib will be explored. In Part A the effect of changing the schedule of prexasertib and cisplatin also will be explored. In Part B the effect of changing the schedule of prexasertib and cetuximab also will be explored.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prexasertib + Cisplatin (Part A) | Experimental | Part A: Prexasertib and cisplatin administered intravenously (IV) once every 21 days. Part A2: Prexasertib and cisplatin administered IV every 21 days; G-CSF administered subcutaneously (SC) starting approximately 24 hours after each prexasertib dose every 21 days. Part A3: Cisplatin administered IV on day one and prexasertib administered IV on day two once every 21 days. Part A Expansion: Part A, A2, and/or A3 may be expanded at the recommended dose. Participants may remain on treatment until discontinuation criteria are met. |
|
| Prexasertib + Cetuximab (Part B) | Experimental | Part B: Cetuximab administered IV weekly and prexasertib administered IV once every 14 days. Part B2: Cetuximab administered IV weekly and prexasertib administered IV once every 14 days; G-CSF administered SC starting approximately 24 hours after each prexasertib dose every 14 days. Part B3: Cetuximab administered IV with prexasertib administered IV once every 14 days. Part B Expansion: Part B, B2 and/or B3 may be expanded at the recommended dose. Participants may remain on treatment until discontinuation criteria are met. |
|
| Prexasertib + Pemetrexed (Part C) | Experimental | Part C: Pemetrexed administered IV on day one and prexasertib administered IV on day one and two every 21 days. Participants may remain on treatment until discontinuation criteria are met. |
|
| Prexasertib + 5-FU (Part D) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prexasertib | Drug | Administered IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Maximum Tolerated Dose and Schedule of Prexasertib in Combination with Cisplatin | Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) | |
| Part B: Maximum Tolerated Dose of Prexasertib in Combination with Cetuximab | Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) | |
| Part C: Maximum Tolerated Dose of Prexasertib in Combination with Pemetrexed | Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) | |
| Part D: Maximum Tolerated Dose of Prexasertib in Combination with Fluorouracil (5-FU) | Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) | |
| Part E: Maximum Tolerated Dose of Prexasertib in Combination with LY3023414 | Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Maximum Plasma Concentration of Prexasertib | Cycle 1 Predose through Cycle 2, Day 15 | |
| Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib | Cycle 1 Predose through Cycle 2, Day 15 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Florida Cancer Specialists | Sarasota | Florida | 34232 | United States | ||
| University of Oklahoma Health Sciences Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34559360 | Derived | Moore KN, Hong DS, Patel MR, Pant S, Ulahannan SV, Jones S, Meric-Bernstam F, Wang JS, Aljumaily R, Hamilton EP, Wittchen ES, Wang X, Lin AB, Bendell JC. A Phase 1b Trial of Prexasertib in Combination with Standard-of-Care Agents in Advanced or Metastatic Cancer. Target Oncol. 2021 Sep;16(5):569-589. doi: 10.1007/s11523-021-00835-0. Epub 2021 Sep 24. | |
| 33495309 |
| Label | URL |
|---|---|
| A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer | View source |
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| Experimental |
Part D: Leucovorin administered IV on day one, 5-FU administered IV bolus on day one and by continuous IV on days one to three (46 hours), and prexasertib administered IV on day three every 14 days. Participants may remain on treatment until discontinuation criteria are met. |
|
| Prexasertib + LY3023414 (Part E) | Experimental | Part E: Prexasertib administered IV on day one and LY3023414 administered orally twice daily every 14 days. Part E will be expanded at the recommended dose in participants with advanced or metastatic cancer, participants with PIK3CA mutations (E2 expansion), or with advanced or metastatic ER-negative, PR-negative, and HER-2 non-overexpressing breast cancer (E3 expansion). Participants may remain on treatment until discontinuation criteria are met. |
|
|
| Cisplatin | Drug | Administered IV |
|
| Cetuximab | Drug | Administered IV |
|
|
| G-CSF | Drug | Administered SC |
|
| Pemetrexed | Drug | Administered IV |
|
|
| Fluorouracil | Drug | Administered IV |
|
| LY3023414 | Drug | Administered PO |
|
| Leucovorin | Drug | Administered IV |
|
| Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum) | Cycle 1 Predose through Cycle 2, Day 1 |
| Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum) | Cycle 1 Predose through Cycle 2, Day 1 |
| Pharmacokinetics: Maximum Plasma Concentration of Cetuximab | Cycle 1 Predose through Cycle 3, Day 1 |
| Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed | Cycle 1 Predose through Cycle 1, Day 2 |
| Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed | Cycle 1 Predose through Cycle 1, Day 2 |
| Pharmacokinetics: Maximum Plasma Concentration of 5-FU | Cycle 1 Predose through Cycle 1, Day 3 |
| Pharmacokinetics: Maximum Plasma Concentration of LY3023414 | Cycle 1 Predose through Cycle 2, Day 2 |
| Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414 | Time Frame: Cycle 1 Predose through Cycle 2, Day 2 |
| B2, E2, E3 Dose Expansion: Overall Response Rate | Baseline through disease progression (estimated as up to 24 weeks) or death from any cause |
| B2, E2, E3 Dose Expansion: Disease Control Rate | Baseline through disease progression (estimated as up to 24 weeks) or death from any cause |
| B2, E2, E3 Dose Expansion: Progression-Free Survival | Baseline through disease progression (estimated as up to 24 weeks) or death from any cause |
| B2, E2, E3 Dose Expansion: Duration of Response | Baseline through disease progression (estimated as up to 24 weeks) or death from any cause |
| Oklahoma City |
| Oklahoma |
| 73104 |
| United States |
| Sarah Cannon Research Institute SCRI | Nashville | Tennessee | 37203 | United States |
| Tennessee Oncology PLLC | Nashville | Tennessee | 37203 | United States |
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Hong DS, Moore KN, Bendell JC, Karp DD, Wang JS, Ulahannan SV, Jones S, Wu W, Donoho GP, Ding Y, Capen A, Wang X, Bence Lin A, Patel MR. Preclinical Evaluation and Phase Ib Study of Prexasertib, a CHK1 Inhibitor, and Samotolisib (LY3023414), a Dual PI3K/mTOR Inhibitor. Clin Cancer Res. 2021 Apr 1;27(7):1864-1874. doi: 10.1158/1078-0432.CCR-20-3242. Epub 2021 Jan 25. |
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| D015179 | Colorectal Neoplasms |
| D001943 | Breast Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000608121 | prexasertib |
| D002945 | Cisplatin |
| D000068818 | Cetuximab |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D000068437 | Pemetrexed |
| D005472 | Fluorouracil |
| C000621566 | LY3023414 |
| D002955 | Leucovorin |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000600 | Amino Acids, Dicarboxylic |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
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