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: * cisplatin (Part A) * cetuximab (Part B) * pemetrexed (Part C) * fluorouracil (Part D) * LY3023414 (Part E) \[An inhibitor of phosphoinositide 3-kinase alpha (PI3K alpha) and mammalian target of rapamycin (mTOR), DNA-dependent protein kinase (DNA-PK), and other class I phosphoinositide 3-kinase (PI3K) family members\] 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
Florida Cancer Specialists
Sarasota, Florida, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, United States
Tennessee Oncology PLLC
Nashville, Tennessee, United States
Part A: Maximum Tolerated Dose and Schedule of Prexasertib in Combination with Cisplatin
Time frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Part B: Maximum Tolerated Dose of Prexasertib in Combination with Cetuximab
Time frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Part C: Maximum Tolerated Dose of Prexasertib in Combination with Pemetrexed
Time frame: 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)
Time frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Part E: Maximum Tolerated Dose of Prexasertib in Combination with LY3023414
Time frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Pharmacokinetics: Maximum Plasma Concentration of Prexasertib
Time frame: Cycle 1 Predose through Cycle 2, Day 15
Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib
Time frame: Cycle 1 Predose through Cycle 2, Day 15
Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum)
Time frame: Cycle 1 Predose through Cycle 2, Day 1
Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum)
Time frame: Cycle 1 Predose through Cycle 2, Day 1
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
NONE
Enrollment
167
Administered SC
Administered IV
Administered IV
Administered PO
Administered IV
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Pharmacokinetics: Maximum Plasma Concentration of Cetuximab
Time frame: Cycle 1 Predose through Cycle 3, Day 1
Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed
Time frame: Cycle 1 Predose through Cycle 1, Day 2
Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed
Time frame: Cycle 1 Predose through Cycle 1, Day 2
Pharmacokinetics: Maximum Plasma Concentration of 5-FU
Time frame: Cycle 1 Predose through Cycle 1, Day 3
Pharmacokinetics: Maximum Plasma Concentration of LY3023414
Time frame: Cycle 1 Predose through Cycle 2, Day 2
Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414
Time frame: Time Frame: Cycle 1 Predose through Cycle 2, Day 2
B2, E2, E3 Dose Expansion: Overall Response Rate
Time frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause
B2, E2, E3 Dose Expansion: Disease Control Rate
Time frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause
B2, E2, E3 Dose Expansion: Progression-Free Survival
Time frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause
B2, E2, E3 Dose Expansion: Duration of Response
Time frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause