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Advanced CancerPhase 1NCT01287520

A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

A Phase 1 study testing LY2090314, pemetrexed and Carboplatin in people with Advanced Cancer, run by Eli Lilly and Company at 2 sites in United States.

Completed

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

Official record
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Trial summary

The purpose of this study is to determine a recommended Phase 2 dose and dosing regimen of LY2090314 in combination with pemetrexed and carboplatin in patients with advanced/metastatic cancer. Read more about this study

Who is it for?
Ages 25 years and older
Conditions the study is for
Advanced Cancer
What is being tested?
LY2090314, pemetrexed and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
2 sitesUnited States
Study dates
Nov 2007to Apr 2011
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

  • Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Have a life expectancy of greater than or equal to 12 weeks
  • Males and females with reproductive potential agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug
  • Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease for which no proven effective therapy exists
  • Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
  • Have adequate hematologic, hepatic, and renal function
  • Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy.

Who cannot join

  • Have received treatment within 30 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication
  • Have serious preexisting medical conditions (left to discretion of investigator)
  • Have one of the following conduction abnormalities: Corrected time between start of Q wave and end of T wave (QTc) prolongation >450 millisecond (msec) on screening electrocardiogram (ECG), previous history of QTc prolongation with another medication that required discontinuation, congenital long-QT-syndrome, or left bundle branch block (LBBB)
  • Are taking any concomitant medication that may cause QTc prolongation, or induce Torsades de Pointes
  • Have systolic blood pressure greater than or equal to 140 millimeters of Mercury (mm Hg), and diastolic blood pressure greater than or equal to 90 mm Hg that is not controlled by medical therapy
  • Have serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class II or higher; have history of arrhythmia that is symptomatic or requires treatment
Show all 11Show fewer
  • Have chronic atrial fibrillation and/or bradycardia
  • Have uncorrected electrolyte disorders including potassium <3.4 molar equivalent per liter (mEq/L) (<3.4 millimole per liter [mmol/l]), calcium <8.4 milligram per deciliter (mg/dL) (2.1 mmol/L), or magnesium <1.2 mg/dL (<0.62 mmol/L)
  • Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required)
  • Have a hematologic malignancy
  • Females who are pregnant or lactating

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Nashville, Tennessee

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Tampa, Florida

Other trials in United States

About this study

Official title: Phase 1 Dose Escalation Study of LY2090314 in Patients With Advanced or Metastatic Cancer in Combination With Pemetrexed and Carboplatin

The purpose of this study is to determine a recommended Phase 2 dose and dosing regimen of LY2090314 in combination with pemetrexed and carboplatin in patients with advanced/metastatic cancer. Part A of this study will consist of dose escalation of the study regimen, and Part B will consist of an expanded cohort to confirm the dose provided from Part A.

Conditions
Advanced Cancer
Being tested
LY2090314, pemetrexed, Carboplatin, ranitidine

What participants receive

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

  • LY2090314Drug

    Administered intravenously

  • pemetrexedDrug

    Also called Alimta, LY231514

    Administered intravenously

  • CarboplatinDrug

    Administered intravenously

  • ranitidineOther

    Per I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine given as pretreatment to LY2090314 for stomach pain.

Study groups in NCT01287520
Study groupRoleWhat they receive
LY2090314/pemetrexed/carboplatinExperimentalPart A, Cycle 1 (28 days): Intravenous doses of LY2090314 starting at 10 milligram (mg) were given on Day 1 followed by 10 mg LY2090314, 500 milligram per square meter (mg/m^2) pemetrexed (intravenous dose), and 5 or 6 area under the concentration-time curve (AUC) intravenous dose of carboplatin on Day 8. Part A, Cycle 2 (21 days): Pemetrexed and carboplatin given on Day 1 at the same dose administered in Cycle 1. Part A, Cycle 3 (21 days) and beyond: LY2090314, Pemetrexed and carboplatin were given on Day 1 at the same dose administered in Cycle 1. LY2090314 doses were escalated until the maximum tolerated dose (MTD) was reached. Part B: Dose determined in Part A was administered. Participants were allowed to continue the combination treatment if they were receiving therapeutic benefit until they fulfilled one of the criteria for discontinuation.
Receives: Drug: LY2090314; Drug: pemetrexed; Drug: Carboplatin; Other: ranitidine

What is being measured

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

  1. Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD])

    Recommended Phase 2 MTD was determined, when a dose limiting toxicity (DLT) occurred in 1 of 3 participants, the cohort was to be expanded to 6 participants. If a DLT occurred in 2 or more participants, accrual to the cohort was stopped, as the MTD was exceeded. A DLT was defined as an adverse event (AE) occurring in Cycle 1 (28 days) that was possibly related to study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0, ≥Grade 3 nonhematologic toxicity (except for nausea/vomiting without maximal symptomatic/prophylactic treatment) possibly or likely related to the study medication;CTCAE Grade 4 hematological toxicity of >5 days duration; Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; CTCAE ≥Grade 2 thrombocytopenia plus bleeding; CTCAE ≥Grade 3 prolonged QTc interval.

    Measured: Baseline up to Day 28 (Cycle 1)

Secondary outcomes (10)

  1. Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of LY2090314

    AUC0-∞ was calculated from the area under the concentration versus time curve from time 0 to infinity of LY2090314 when administered alone.

    Measured: Cycle 1 Day 1 of a 28 day cycle

  2. PK Parameter: AUC0-∞ of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)

    AUC0-∞ was calculated from the area under the concentration versus time curves of LY2090314 from time zero to infinity when coadministered with Pem and Carb.

    Measured: Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle

  3. PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314

    Measured: Cycle 1 Day 1 of a 28-day cycle

  4. PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)

    Measured: Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle

  5. Number of Participants With Best Overall Tumor Response

    Best overall observed tumor response at any point during the study until disease progression/recurrence defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as at least 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria.

    Measured: Baseline up to Cycle 9 (Cycle 1 was 28 days, Cycles 2 to 9 were 21 days)

  6. Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of Pemetrexed (Pem)

    AUC0-∞ was calculated from the area under the concentration versus time curves of Pem given as a single dose with Carb (doublet therapy) and when co-administered with Carb and LY2090314 (triplet therapy).

    Measured: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle

  7. PK Parameter: Maximum Plasma Concentration (Cmax) of Pemetrexed (Pem)

    Cmax of Pem given as a single dose with Carb (doublet therapy) and when coadministered with Carb and LY2090314 (triplet therapy).

    Measured: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle

  8. PK Parameter: AUC0-∞ of Free Carboplatin (Carb)

    AUC0-∞ of free Carb was calculated from the area under the concentration versus time curves of Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy).

    Measured: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle

  9. PK Parameter: Cmax of Free Carboplatin

    Cmax of free Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy).

    Measured: Cycle 1, Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle

  10. Pharmacodynamic (PD) Changes in Beta-Catenin (β-catenin)

    PD change from baseline to endpoint (up to Cycle 9) in β-catenin levels in peripheral blood mononuclear cells (PBMCs) following the administration of LY2090314 given alone and in combination with Pem and Carb. This outcome measure was not analyzed due to insufficient data.

    Measured: Baseline, Cycle 1 , Day 1 of a 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycles

Timeline

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

  1. First posted1 Feb 2011 (estimated)
  2. Study startNov 2007
  3. Primary completionApr 2011
  4. Study completionApr 2011

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01287520
Sponsor's protocol ID
11613
Other IDs
I2H-MC-JWYA
Status last verified
Oct 2018
First submitted
28 Jan 2011
Last updated
25 Feb 2019
Data monitoring committee
No

Publications

  • Gray JE, Infante JR, Brail LH, Simon GR, Cooksey JF, Jones SF, Farrington DL, Yeo A, Jackson KA, Chow KH, Zamek-Gliszczynski MJ, Burris HA 3rd. A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin. Invest New Drugs. 2015 Dec;33(6):1187-96. doi: 10.1007/s10637-015-0278-7. Epub 2015 Sep 25.

    PubMed 26403509

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LY2090314, pemetrexed and Carboplatin in people with Advanced Cancer, run by Eli Lilly and Company at 2 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 7 inclusion and 11 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 25 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

Yes. Results are posted in the registry (first posted 25 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD]) (time frame: Baseline up to Day 28 (Cycle 1)). 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 NCT01287520, which also lists 1 linked publication.

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 25 Feb 2019.

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