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A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

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ClinicalTrials.gov Identifier: NCT01287520
Recruitment Status : Completed
First Posted : February 1, 2011
Results First Posted : February 25, 2019
Last Update Posted : February 25, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: LY2090314 Drug: pemetrexed Drug: Carboplatin Other: ranitidine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Dose Escalation Study of LY2090314 in Patients With Advanced or Metastatic Cancer in Combination With Pemetrexed and Carboplatin
Study Start Date : November 2007
Actual Primary Completion Date : April 2011
Actual Study Completion Date : April 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: LY2090314/pemetrexed/carboplatin

Part 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.

Drug: LY2090314
Administered intravenously

Drug: pemetrexed
Administered intravenously
Other Names:
  • Alimta
  • LY231514

Drug: Carboplatin
Administered intravenously

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




Primary Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT01287520


Locations
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United States, Florida
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
United States, 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.
Nashville, Tennessee, United States
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01287520     History of Changes
Other Study ID Numbers: 11613
I2H-MC-JWYA ( Other Identifier: Eli Lilly and Company )
First Posted: February 1, 2011    Key Record Dates
Results First Posted: February 25, 2019
Last Update Posted: February 25, 2019
Last Verified: October 2018
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes
Carboplatin
Pemetrexed
Ranitidine
Ranitidine bismuth citrate
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs