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Neoplasm MetastasisPhase 1NCT02124148

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

A Phase 1 study testing Prexasertib, Cisplatin and Cetuximab in people with Neoplasm Metastasis and Colorectal Neoplasms, run by Eli Lilly and Company at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Prexasertib, Cisplatin and Cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
167 participants
Where
5 sitesUnited States
Study dates
18 Jun 2014to 13 Feb 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Sarah Cannon Research Institute SCRI

    Nashville, Tennessee, 37203

  • Tennessee Oncology PLLC

    Nashville, Tennessee, 37203

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

Other trials in United States

About this study

Official title: A Phase 1b Trial of LY2606368 in Combination With Chemotherapy or Targeted Agents in Advanced and/or Metastatic Tumors

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.

Read the 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.

Being tested
Prexasertib, Cisplatin, Cetuximab, G-CSF, Pemetrexed
Keywords
cancer
Medical subject headings
Neoplasm Metastasis, Colorectal Neoplasms, Breast Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrexasertibDrug

    Also called LY2606368

    Administered IV

  • CisplatinDrug

    Administered IV

  • CetuximabDrug

    Also called Erbitux

    Administered IV

  • G-CSFDrug

    Administered SC

  • PemetrexedDrug

    Also called Alimta

    Administered IV

  • FluorouracilDrug

    Administered IV

  • LY3023414Drug

    Administered PO

  • LeucovorinDrug

    Administered IV

Study groups in NCT02124148
Study groupRoleWhat they receive
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.
Receives: Drug: Prexasertib; Drug: Cisplatin; Drug: 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.
Receives: Drug: Prexasertib; Drug: Cetuximab; Drug: 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.
Receives: Drug: Prexasertib; Drug: 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.
Receives: Drug: Prexasertib; Drug: Fluorouracil; Drug: 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.
Receives: Drug: Prexasertib; Drug: LY3023414

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Maximum Tolerated Dose and Schedule of Prexasertib in Combination with Cisplatin

    Measured: 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

    Measured: 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

    Measured: 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)

    Measured: 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

    Measured: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)

Secondary outcomes (14)

  1. Pharmacokinetics: Maximum Plasma Concentration of Prexasertib

    Measured: Cycle 1 Predose through Cycle 2, Day 15

  2. Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib

    Measured: Cycle 1 Predose through Cycle 2, Day 15

  3. Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum)

    Measured: Cycle 1 Predose through Cycle 2, Day 1

  4. Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum)

    Measured: Cycle 1 Predose through Cycle 2, Day 1

  5. Pharmacokinetics: Maximum Plasma Concentration of Cetuximab

    Measured: Cycle 1 Predose through Cycle 3, Day 1

  6. Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed

    Measured: Cycle 1 Predose through Cycle 1, Day 2

  7. Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed

    Measured: Cycle 1 Predose through Cycle 1, Day 2

  8. Pharmacokinetics: Maximum Plasma Concentration of 5-FU

    Measured: Cycle 1 Predose through Cycle 1, Day 3

  9. Pharmacokinetics: Maximum Plasma Concentration of LY3023414

    Measured: Cycle 1 Predose through Cycle 2, Day 2

  10. Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414

    Measured: Time Frame: Cycle 1 Predose through Cycle 2, Day 2

  11. B2, E2, E3 Dose Expansion: Overall Response Rate

    Measured: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause

  12. B2, E2, E3 Dose Expansion: Disease Control Rate

    Measured: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause

  13. B2, E2, E3 Dose Expansion: Progression-Free Survival

    Measured: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause

  14. B2, E2, E3 Dose Expansion: Duration of Response

    Measured: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2014 (estimated)
  2. Study start18 Jun 2014
  3. Primary completion13 Feb 2020
  4. Study completion13 Feb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
167 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02124148
Sponsor's protocol ID
15295
Other IDs
I4D-MC-JTJF
Status last verified
Mar 2020
First submitted
24 Apr 2014
Last updated
1 Apr 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 34559360

  • 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.

    PubMed 33495309

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Prexasertib, Cisplatin and Cetuximab in people with Neoplasm Metastasis and Colorectal Neoplasms, run by Eli Lilly and Company at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02124148, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2020.

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