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A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With 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: NCT02124148
Recruitment Status : Completed
First Posted : April 28, 2014
Last Update Posted : April 1, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE April 24, 2014
First Posted Date  ICMJE April 28, 2014
Last Update Posted Date April 1, 2020
Actual Study Start Date  ICMJE June 18, 2014
Actual Primary Completion Date February 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2016)
  • 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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2014)
  • Parts A and C: Maximum Tolerated Dose of LY2606368 in Combination with Cisplatin [ Time Frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) ]
  • Parts B and D: Maximum Tolerated Dose of LY2606368 in Combination with Cetuximab [ Time Frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2017)
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2014)
  • Pharmacokinetics: Maximum Concentration of LY2606368 [ Time Frame: Cycle 1 Predose through Cycle 2, Day 15 ]
  • Pharmacokinetics: Area Under the Concentration Curve of LY2606368 [ Time Frame: Cycle 1 Predose through Cycle 2, Day 15 ]
  • Part D: Overall Response Rate [ Time Frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause ]
  • Part D: Disease Control Rate [ Time Frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause ]
  • Part D: Progression-Free Survival [ Time Frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause ]
  • Part D: Duration of Response [ Time Frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer
Official Title  ICMJE A Phase 1b Trial of LY2606368 in Combination With Chemotherapy or Targeted Agents in Advanced and/or Metastatic Tumors
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neoplasm Metastasis
  • Colorectal Neoplasms
  • Breast Cancer
Intervention  ICMJE
  • Drug: Prexasertib
    Administered IV
    Other Name: LY2606368
  • Drug: Cisplatin
    Administered IV
  • Drug: Cetuximab
    Administered IV
    Other Name: Erbitux
  • Drug: G-CSF
    Administered SC
  • Drug: Pemetrexed
    Administered IV
    Other Name: Alimta
  • Drug: Fluorouracil
    Administered IV
  • Drug: LY3023414
    Administered PO
  • Drug: Leucovorin
    Administered IV
Study Arms  ICMJE
  • Experimental: Prexasertib + Cisplatin (Part A)

    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.

    Interventions:
    • Drug: Prexasertib
    • Drug: Cisplatin
    • Drug: G-CSF
  • Experimental: Prexasertib + Cetuximab (Part B)

    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.

    Interventions:
    • Drug: Prexasertib
    • Drug: Cetuximab
    • Drug: G-CSF
  • Experimental: Prexasertib + Pemetrexed (Part C)

    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.

    Interventions:
    • Drug: Prexasertib
    • Drug: Pemetrexed
  • Experimental: Prexasertib + 5-FU (Part D)

    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.

    Interventions:
    • Drug: Prexasertib
    • Drug: Fluorouracil
    • Drug: Leucovorin
  • Experimental: Prexasertib + LY3023414 (Part E)

    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.

    Interventions:
    • Drug: Prexasertib
    • Drug: LY3023414
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 5, 2019)
167
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2014)
70
Actual Study Completion Date  ICMJE February 13, 2020
Actual Primary Completion Date February 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02124148
Other Study ID Numbers  ICMJE 15295
I4D-MC-JTJF ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: 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
PRS Account Eli Lilly and Company
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP