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A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer

Primary Purpose

Neoplasm Metastasis, Colorectal Neoplasms, Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Prexasertib
Cisplatin
Cetuximab
G-CSF
Pemetrexed
Fluorouracil
LY3023414
Leucovorin
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm Metastasis focused on measuring cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Must be appropriate candidate for experimental therapy, as determined by investigator, after available standard therapies have failed
  • Have adequate organ function
  • Prior Therapies: Systemic treatments: must have discontinued previous systemic treatments for cancer and recovered from the acute effects of therapy. Participants must have discontinued mitomycin-C or nitrosourea therapy at least 42 days and have discontinued any cytotoxic therapies at least 28 days prior to study enrollment. Radiation therapy and surgery: must be completed at least 4 weeks before study enrollment
  • All parts except Part B, Part E2, and Part E3 dose expansion: Must have diagnosis of cancer that is advanced or metastatic
  • Part B dose expansion: Must have confirmed Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type colorectal cancer that is metastatic or recurrent and has failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant of irinotecan or oxaliplatin
  • Part E2 dose expansion: must have cancer that is advanced or metastatic and have prior documentation of a mutation of PIK3CA
  • Part E3 dose expansion: must have advanced or metastatic ER-negative, PR-negative, and HER-2 non-overexpressing breast cancer
  • Must be available during the duration of the study and willing to follow the study procedures
  • Parts A and B: If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for six months following the last dose of study drug
  • Parts C, D and E: If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for three months following the last dose of study drug
  • If the participant is a female of childbearing potential, must have had a negative serum or urine pregnancy test within 14 days of the first dose of study drug and must not be breast feeding
  • Part E: Are able to swallow capsules or tablets

Exclusion Criteria:

  • Have received more than 2 previous lines of cytotoxic chemotherapy (if receiving cisplatin, 5-FU or pemetrexed)
  • Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment
  • Must not have an active symptomatic fungal, bacterial or viral infection, including human immunodeficiency virus (HIV) or Hepatitis A, B, or C
  • Must not have a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months
  • Must not have a family history of long QTc syndrome
  • Must not have a serotonin-secreting carcinoid tumor or a prior history of drug-induced serotonin syndrome
  • Must not have acute leukemia
  • Part E: Have insulin-dependent (type I) diabetes or a history of gestational diabetes
  • Part E: Prior treatment with a PI3K/mTOR inhibitor

Sites / Locations

  • Florida Cancer Specialists
  • University of Oklahoma Health Sciences Center
  • Sarah Cannon Research Institute SCRI
  • Tennessee Oncology PLLC
  • University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Prexasertib + Cisplatin (Part A)

Prexasertib + Cetuximab (Part B)

Prexasertib + Pemetrexed (Part C)

Prexasertib + 5-FU (Part D)

Prexasertib + LY3023414 (Part E)

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Part A: Maximum Tolerated Dose and Schedule of Prexasertib in Combination with Cisplatin
Part B: Maximum Tolerated Dose of Prexasertib in Combination with Cetuximab
Part C: Maximum Tolerated Dose of Prexasertib in Combination with Pemetrexed
Part D: Maximum Tolerated Dose of Prexasertib in Combination with Fluorouracil (5-FU)
Part E: Maximum Tolerated Dose of Prexasertib in Combination with LY3023414

Secondary Outcome Measures

Pharmacokinetics: Maximum Plasma Concentration of Prexasertib
Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib
Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum)
Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum)
Pharmacokinetics: Maximum Plasma Concentration of Cetuximab
Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed
Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed
Pharmacokinetics: Maximum Plasma Concentration of 5-FU
Pharmacokinetics: Maximum Plasma Concentration of LY3023414
Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414
B2, E2, E3 Dose Expansion: Overall Response Rate
B2, E2, E3 Dose Expansion: Disease Control Rate
B2, E2, E3 Dose Expansion: Progression-Free Survival
B2, E2, E3 Dose Expansion: Duration of Response

Full Information

First Posted
April 24, 2014
Last Updated
March 30, 2020
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT02124148
Brief Title
A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer
Official Title
A Phase 1b Trial of LY2606368 in Combination With Chemotherapy or Targeted Agents in Advanced and/or Metastatic Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
June 18, 2014 (Actual)
Primary Completion Date
February 13, 2020 (Actual)
Study Completion Date
February 13, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm Metastasis, Colorectal Neoplasms, Breast Cancer
Keywords
cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
167 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prexasertib + Cisplatin (Part A)
Arm Type
Experimental
Arm Description
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.
Arm Title
Prexasertib + Cetuximab (Part B)
Arm Type
Experimental
Arm Description
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.
Arm Title
Prexasertib + Pemetrexed (Part C)
Arm Type
Experimental
Arm Description
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.
Arm Title
Prexasertib + 5-FU (Part D)
Arm Type
Experimental
Arm Description
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.
Arm Title
Prexasertib + LY3023414 (Part E)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Prexasertib
Other Intervention Name(s)
LY2606368
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
G-CSF
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Other Intervention Name(s)
Alimta
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
LY3023414
Intervention Description
Administered PO
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Secondary Outcome Measure Information:
Title
Pharmacokinetics: Maximum Plasma Concentration of Prexasertib
Time Frame
Cycle 1 Predose through Cycle 2, Day 15
Title
Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib
Time Frame
Cycle 1 Predose through Cycle 2, Day 15
Title
Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum)
Time Frame
Cycle 1 Predose through Cycle 2, Day 1
Title
Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum)
Time Frame
Cycle 1 Predose through Cycle 2, Day 1
Title
Pharmacokinetics: Maximum Plasma Concentration of Cetuximab
Time Frame
Cycle 1 Predose through Cycle 3, Day 1
Title
Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed
Time Frame
Cycle 1 Predose through Cycle 1, Day 2
Title
Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed
Time Frame
Cycle 1 Predose through Cycle 1, Day 2
Title
Pharmacokinetics: Maximum Plasma Concentration of 5-FU
Time Frame
Cycle 1 Predose through Cycle 1, Day 3
Title
Pharmacokinetics: Maximum Plasma Concentration of LY3023414
Time Frame
Cycle 1 Predose through Cycle 2, Day 2
Title
Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414
Time Frame
Time Frame: Cycle 1 Predose through Cycle 2, Day 2
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must be appropriate candidate for experimental therapy, as determined by investigator, after available standard therapies have failed Have adequate organ function Prior Therapies: Systemic treatments: must have discontinued previous systemic treatments for cancer and recovered from the acute effects of therapy. Participants must have discontinued mitomycin-C or nitrosourea therapy at least 42 days and have discontinued any cytotoxic therapies at least 28 days prior to study enrollment. Radiation therapy and surgery: must be completed at least 4 weeks before study enrollment All parts except Part B, Part E2, and Part E3 dose expansion: Must have diagnosis of cancer that is advanced or metastatic Part B dose expansion: Must have confirmed Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type colorectal cancer that is metastatic or recurrent and has failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant of irinotecan or oxaliplatin Part E2 dose expansion: must have cancer that is advanced or metastatic and have prior documentation of a mutation of PIK3CA Part E3 dose expansion: must have advanced or metastatic ER-negative, PR-negative, and HER-2 non-overexpressing breast cancer Must be available during the duration of the study and willing to follow the study procedures Parts A and B: If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for six months following the last dose of study drug Parts C, D and E: If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for three months following the last dose of study drug If the participant is a female of childbearing potential, must have had a negative serum or urine pregnancy test within 14 days of the first dose of study drug and must not be breast feeding Part E: Are able to swallow capsules or tablets Exclusion Criteria: Have received more than 2 previous lines of cytotoxic chemotherapy (if receiving cisplatin, 5-FU or pemetrexed) Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment Must not have an active symptomatic fungal, bacterial or viral infection, including human immunodeficiency virus (HIV) or Hepatitis A, B, or C Must not have a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months Must not have a family history of long QTc syndrome Must not have a serotonin-secreting carcinoid tumor or a prior history of drug-induced serotonin syndrome Must not have acute leukemia Part E: Have insulin-dependent (type I) diabetes or a history of gestational diabetes Part E: Prior treatment with a PI3K/mTOR inhibitor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Florida Cancer Specialists
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Sarah Cannon Research Institute SCRI
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Tennessee Oncology PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34559360
Citation
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.
Results Reference
derived
PubMed Identifier
33495309
Citation
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.
Results Reference
derived
Links:
URL
https://www.lillytrialguide.com/en-US/studies/solid-tumor/JTJF#?postal=
Description
A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer

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A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer

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