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Completed

NCT Number: NCT01287520

A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

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.

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Key information

Conditions

Age range

25 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

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, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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
  • 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

Treatment and study plan

LY2090314

Drug

Administered intravenously

Pemetrexed

Drug

Administered intravenously

Other names: Alimta, LY231514

carboplatin

Drug

Administered intravenously

ranitidine

Other

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

Primary outcomes

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

    Time frame: Baseline up to Day 28 (Cycle 1)

    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.

Secondary outcomes

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

    Time frame: Cycle 1 Day 1 of a 28 day cycle

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

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

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

    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.

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

    Time frame: 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)

    Time frame: 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

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

    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.

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

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

    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).

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

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

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

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

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

    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).

  9. PK Parameter: Cmax of Free Carboplatin

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

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

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

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

    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.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Important dates

Study start
2007
Primary completion
2011
Study completion
2011
First posted
Feb 1, 2011
Registry last updated
Feb 25, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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