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

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ClinicalTrials.gov Identifier: NCT02124148
Recruitment Status : Active, not recruiting
First Posted : April 28, 2014
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Neoplasm Metastasis Colorectal Neoplasms Breast Cancer Drug: Prexasertib Drug: Cisplatin Drug: Cetuximab Drug: G-CSF Drug: Pemetrexed Drug: Fluorouracil Drug: LY3023414 Drug: Leucovorin Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 167 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Trial of LY2606368 in Combination With Chemotherapy or Targeted Agents in Advanced and/or Metastatic Tumors
Actual Study Start Date : June 18, 2014
Estimated Primary Completion Date : February 27, 2020
Estimated Study Completion Date : February 27, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

Drug: Prexasertib
Administered IV
Other Name: LY2606368

Drug: Cisplatin
Administered IV

Drug: G-CSF
Administered SC

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.

Drug: Prexasertib
Administered IV
Other Name: LY2606368

Drug: Cetuximab
Administered IV
Other Name: Erbitux

Drug: G-CSF
Administered SC

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.

Drug: Prexasertib
Administered IV
Other Name: LY2606368

Drug: Pemetrexed
Administered IV
Other Name: Alimta

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.

Drug: Prexasertib
Administered IV
Other Name: LY2606368

Drug: Fluorouracil
Administered IV

Drug: Leucovorin
Administered IV

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.

Drug: Prexasertib
Administered IV
Other Name: LY2606368

Drug: LY3023414
Administered PO




Primary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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 Measures :
  1. Pharmacokinetics: Maximum Plasma Concentration of Prexasertib [ Time Frame: Cycle 1 Predose through Cycle 2, Day 15 ]
  2. Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib [ Time Frame: Cycle 1 Predose through Cycle 2, Day 15 ]
  3. Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum) [ Time Frame: Cycle 1 Predose through Cycle 2, Day 1 ]
  4. Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum) [ Time Frame: Cycle 1 Predose through Cycle 2, Day 1 ]
  5. Pharmacokinetics: Maximum Plasma Concentration of Cetuximab [ Time Frame: Cycle 1 Predose through Cycle 3, Day 1 ]
  6. Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed [ Time Frame: Cycle 1 Predose through Cycle 1, Day 2 ]
  7. Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed [ Time Frame: Cycle 1 Predose through Cycle 1, Day 2 ]
  8. Pharmacokinetics: Maximum Plasma Concentration of 5-FU [ Time Frame: Cycle 1 Predose through Cycle 1, Day 3 ]
  9. Pharmacokinetics: Maximum Plasma Concentration of LY3023414 [ Time Frame: Cycle 1 Predose through Cycle 2, Day 2 ]
  10. Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414 [ Time Frame: Time Frame: Cycle 1 Predose through Cycle 2, Day 2 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02124148


Locations
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United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, United States, 37203
Tennessee Oncology PLLC
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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

Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02124148     History of Changes
Other Study ID Numbers: 15295
I4D-MC-JTJF ( Other Identifier: Eli Lilly and Company )
First Posted: April 28, 2014    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 1, 2019
Keywords provided by Eli Lilly and Company:
cancer
Additional relevant MeSH terms:
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Neoplasm Metastasis
Colorectal Neoplasms
Neoplasms
Neoplastic Processes
Pathologic Processes
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cisplatin
Fluorouracil
Cetuximab
Pemetrexed
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors