Clinical Trials /

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

NCT02124148

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Cancer
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 15295
  • SECONDARY ID: I4D-MC-JTJF
  • NCT ID: NCT02124148

Conditions

  • Neoplasm Metastasis
  • Colorectal Neoplasms
  • Breast Cancer

Interventions

DrugSynonymsArms
PrexasertibLY2606368Prexasertib + Cisplatin (Part A)
CisplatinPrexasertib + Cisplatin (Part A)
CetuximabErbituxPrexasertib + Cetuximab (Part B)
G-CSFPrexasertib + Cisplatin (Part A)
PemetrexedAlimtaPrexasertib + Pemetrexed (Part C)
FluorouracilPrexasertib + 5-FU (Part D)
LY3023414Prexasertib + LY3023414 (Part E)
LeucovorinPrexasertib + 5-FU (Part D)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Prexasertib + Cisplatin (Part A)ExperimentalPart 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
  • Cisplatin
  • G-CSF
Prexasertib + Cetuximab (Part B)ExperimentalPart 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
  • Cetuximab
  • G-CSF
Prexasertib + Pemetrexed (Part C)ExperimentalPart 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
  • Pemetrexed
Prexasertib + 5-FU (Part D)ExperimentalPart 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
  • Fluorouracil
  • Leucovorin
Prexasertib + LY3023414 (Part E)ExperimentalPart 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.
  • Prexasertib
  • LY3023414

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetics: Maximum Plasma Concentration of Prexasertib
Time Frame:Cycle 1 Predose through Cycle 2, Day 15
Safety Issue:
Description:
Measure:Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib
Time Frame:Cycle 1 Predose through Cycle 2, Day 15
Safety Issue:
Description:
Measure:Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum)
Time Frame:Cycle 1 Predose through Cycle 2, Day 1
Safety Issue:
Description:
Measure:Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum)
Time Frame:Cycle 1 Predose through Cycle 2, Day 1
Safety Issue:
Description:
Measure:Pharmacokinetics: Maximum Plasma Concentration of Cetuximab
Time Frame:Cycle 1 Predose through Cycle 3, Day 1
Safety Issue:
Description:
Measure:Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed
Time Frame:Cycle 1 Predose through Cycle 1, Day 2
Safety Issue:
Description:
Measure:Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed
Time Frame:Cycle 1 Predose through Cycle 1, Day 2
Safety Issue:
Description:
Measure:Pharmacokinetics: Maximum Plasma Concentration of 5-FU
Time Frame:Cycle 1 Predose through Cycle 1, Day 3
Safety Issue:
Description:
Measure:Pharmacokinetics: Maximum Plasma Concentration of LY3023414
Time Frame:Cycle 1 Predose through Cycle 2, Day 2
Safety Issue:
Description:
Measure:Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414
Time Frame:Time Frame: Cycle 1 Predose through Cycle 2, Day 2
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • cancer

Last Updated