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Completed

NCT Number: NCT01341457

A Study of LY2603618 in Combination With Gemcitabine in Participants With Solid Tumors

The primary objective of this study is to evaluate the safety and tolerability of LY2603618 in combination with the standard dose of gemcitabine up to the global recommended dose of LY2603618 in Japanese participants with solid advanced or metastatic tumors.

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Key information

Conditions

Age range

20 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.

Chiba, 277-8577, Japan

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Have histological or cytological or imaging evidence of a diagnosis of cancer that is advanced and/or metastatic disease
  • Participant who is planned to have gemcitabine therapy at the proposed doses because he/she was not able to benefit from standard therapy and/or therapies known to provide clinical benefit or there is no standard therapy for the advanced and/or metastatic disease globally
  • Have given written informed consent prior to any study-specific procedures
  • Have adequate hematologic, hepatic and renal function
  • Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Have discontinued all previous therapies for cancer, including chemotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 30 days (42 days for mitomycin C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy
  • Prior radiation therapy for treatment of cancer is allowed to less than 25% of the bone marrow, and participants must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 30 days prior to study enrollment
  • Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months after the last infusion of study drug
  • Females with child bearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have had a negative urine pregnancy test less than 7 days prior to the enrollment
  • Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
  • Have an estimated life expectancy of at least 12 weeks

Exclusion criteria

  • Are currently enrolled in, or discontinued within the last 30 days from, a clinical study involving an off-label use of an investigational drug or device (other than the study drug used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Have serious preexisting medical conditions or serious concomitant systemic disorders that would compromise the safety of the participant or his/her ability to complete the study
  • Have interstitial pneumonitis or pulmonary fibrosis, or previous history of them
  • Have symptomatic central nervous system malignancy or metastasis
  • Have current active infection
  • Females who are pregnant or lactating
  • Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb)
  • Participants with acute or chronic leukemia or with any other disease likely to have a significant bone marrow infiltration
  • Have previously completed or withdrawn from this study or any other study investigating LY2603618 or any other checkpoint kinase (Chk1) inhibitor
  • Have known allergy to gemcitabine or LY2603618 or any ingredient of gemcitabine or LY2603618 (like Captisol®)
  • Have an abnormal electrocardiogram (ECG) result that would put the participant at unnecessary risk in the opinion of the investigator

Treatment and study plan

LY2603618

Drug

Administered intravenously

Gemcitabine

Drug

Administered intravenously

Other names: LY188011

Primary outcomes

  1. Number of Participants With Dose Limiting Toxicity (DLT)

    Time frame: Cycle 1 (28 Days)

    DLT is defined as adverse event (AE) during Cycle 1 (Days 1 through 28) that was possibly related to the study drug and toxicities considered by the investigator as dose limiting. A summary of other nonserious AEs, and all serious adverse events (SAE's), regardless of causality, is located in the Reported Adverse Events section.

Secondary outcomes

  1. Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2603618

    Time frame: Cycle 1 (days 2 and 16) & 2 (day 2): Predose, End of Infusion, 1 hour (h), 3h, 6h, 24h (days 3 and 17), 48h (days 4 and 18 cycle 1 only), 72h (days 5 and 19)

  2. Number of Participants With Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Best Overall Response)

    Time frame: Baseline to Measured Progressive Disease (Up to 52 Months)

    Participants achieved disease control if they had a best overall response of PR, CR or SD according to RECIST v1.1 (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD); PR at least 30% decrease and PD at least 20% increase in the sum of diameter of target lesions; CR: disappearance of all target lesions). Two determinations of PR or better before progression, but not qualifying for a CR, are required for a best response of PR. Best response of SD is defined as disease that does not meet the criteria for CR, PR or PD and has been evaluated at least 6 weeks after the first gemcitabine administration.

  3. PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2603618

    Time frame: Cycle 1 (days 2 and 16) & 2 (day 2): Predose, End of Infusion, 1 hour (h), 3h, 6h, 24h (days 3 and 17), 48h (days 4 and 18 cycle 1 only), 72h (days 5 and 19)

  4. PK: Cmax of Gemcitabine

    Time frame: Cycle 1 (days 1 and 15) & 2 (day 1): Predose, End of Infusion, 10 minutes (m), 30m, 60m, 120m

  5. PK: Cmax of Gemcitabine Metabolite Deoxydifluorouridine (dFdU)

    Time frame: Cycle 1 (days 1 and 15) & 2 (day 1): Predose, End of Infusion, 10 minutes (m), 30m, 60m, 120m

  6. PK: AUC(0-∞) of Gemcitabine

    Time frame: Cycle 1 (days 1 and 15) & 2 (day 1): Predose, End of Infusion, 10 minutes (m), 30m, 60m, 120m

  7. PK: AUC(0-∞) of Gemcitabine Metabolite dFdU

    Time frame: Cycle 1 (days 1 and 15) & 2 (day 1): Predose, End of Infusion, 10 minutes (m), 30m, 60m, 120m

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

A Phase 1 Dose-Escalation Study of LY2603618 in Combination With Gemcitabine in Japanese Patients With Solid Tumors

Important dates

Study start
2011
Primary completion
2013
Study completion
2016
First posted
Apr 25, 2011
Registry last updated
Mar 1, 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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