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A Phase 1 Study in Patients With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01215916
Recruitment Status : Completed
First Posted : October 7, 2010
Results First Posted : March 15, 2019
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE October 5, 2010
First Posted Date  ICMJE October 7, 2010
Results First Submitted Date  ICMJE March 17, 2018
Results First Posted Date  ICMJE March 15, 2019
Last Update Posted Date March 15, 2019
Study Start Date  ICMJE February 2008
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2018)
Recommended Phase 2 Dose [ Time Frame: Baseline to toxicity [up to end of Cycle 1 (cycle = 21 or 28 days)] ]
Based on maximum tolerated dose (MTD) in Cycle 1: highest dose where <33% participants (pts) had dose-limiting toxicity (DLT). DLTs were adverse events (AE) possibly related to study drug or AEs that met any of National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTAE): Grade (G) 4 neutropenia lasting ≥5 days; G4 neutropenia with fever, G4 thrombocytopenia, G3 thrombocytopenia with bleeding, ≥G3 non-hematologic toxicity (except nausea/vomiting and diarrhea controlled by medication; electrolyte toxicity resolved with standard replacement treatment; alopecia; and elevated alanine aminotransferase or aspartate aminotransferase with preexisting hepatic metastasis, if agreed by investigator). Investigators, with sponsor, could declare a DLT if pt experienced increasing toxicity during treatment and it was clear that further treatment would expose pt to excessive risk. Enrollment was stopped during the dose-escalation phase, thus further dose-escalation was not explored.
Original Primary Outcome Measures  ICMJE
 (submitted: October 5, 2010)
Recommended Phase 2 Dose [ Time Frame: Baseline to study completion ]
Change History Complete list of historical versions of study NCT01215916 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2018)
  • Number of Participants With Clinically Significant Effects [ Time Frame: Baseline to end of study (up to 1 year of treatment plus 30-day follow-up) ]
    Clinically significant effects were defined as serious and other non-serious adverse events (AEs) regardless of causality. A summary of serious and all other non-serious AEs is located in the Reported Adverse Events module.
  • Percentage of Participants With a Tumor Response [ Time Frame: Baseline to progressive disease (up to 1 year of treatment plus 30-day follow-up) ]
    Tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and confirmed by repeat assessment. Complete Response (CR) was defined as the disappearance of all target lesions and the normalization of tumor marker levels for non-target lesions; Partial Response (PR) was defined as at least a 30% decrease in the sum of the longest diameter of target lesions. Percentage of participants with a tumor response = (number of participants with CR or PR/number of enrolled participants)*100.
  • Pharmacokinetics, Concentration Maximum (Cmax) of LY573636 [ Time Frame: Cycles 1 and 2 on Day 4 (prior to and at the end of LY573636 infusion, 2 and 4 hours post LY573636 infusion), Day 8 (anytime), Day 15 (anytime) ]
  • Pharmacokinetics, Area Under the Curve (AUC) of LY573636 [ Time Frame: Cycles 1 and 2 on Day 4 (prior to and at the end of LY573636 infusion, 2 and 4 hours post LY573636 infusion), Day 8 (anytime), Day 15 (anytime) ]
    Area under the concentration-time curve above the albumin corrected threshold (AUCalb) is provided for LY573636, which has been found to be highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) LY573636.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2010)
  • Number of Participants With Clinically Significant Effects [ Time Frame: Baseline to study completion ]
  • Number of participants with a tumor response [ Time Frame: Baseline to study completion ]
  • Pharmacokinetics, concentration maximum (Cmax) [ Time Frame: Cycle 1, Cycle 2 ]
  • Pharmacokinetics, Area under the curve (AUC) [ Time Frame: Cycle 1, Cycle 2 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study in Patients With Solid Tumors
Official Title  ICMJE A Phase 1b Study of LY573636-sodium in Combination With Alimta (Pemetrexed) in Patients With Solid Tumors
Brief Summary The primary objective of this study is to determine the maximum tolerated dose (MTD) regimen for the combination therapy of LY573636 and pemetrexed that may be safely administered to patients with a solid tumor that is not amenable to curative therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors
Intervention  ICMJE
  • Drug: LY573636

    Individualized dose is dependent on a patient's height, weight, and gender and is adjusted to target a specific exposure range corrected for a patient's laboratory parameters. Intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days).

    Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.

    Patients are pretreated with folic acid [350 micrograms (µg) to 1000 µg orally, daily], Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone [4 milligrams (mg) orally, twice daily or equivalent].

    Other Name: Tasisulam
  • Drug: Pemetrexed

    375 to 500 milligrams per square meter (mg/m^2), intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days).

    Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.

    Patients are pretreated with folic acid (350 µg to 1000 µg orally, daily), Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone (4 mg orally, twice daily or equivalent).

    Other Names:
    • LY231514
    • Alimta
Study Arms  ICMJE
  • Experimental: Experimental: Pemetrexed followed by LY573636
    Pemetrexed on Day 1 followed by LY573636 on Day 4
    Interventions:
    • Drug: LY573636
    • Drug: Pemetrexed
  • Experimental: Experimental: LY573636 followed by Pemetrexed
    LY573636 on Day 1, pemetrexed on Day 4
    Interventions:
    • Drug: LY573636
    • Drug: Pemetrexed
  • Experimental: Experimental: LY573636 and Pemetrexed on Day 1
    LY573636 and Pemetrexed on Day 1
    Interventions:
    • Drug: LY573636
    • Drug: Pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 1, 2018)
39
Original Estimated Enrollment  ICMJE
 (submitted: October 5, 2010)
30
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • You must have a diagnosis of a solid tumor malignancy that is not amenable to curative therapy
  • You must have a serum albumin level greater than or equal to 3.0 grams per deciliter (g/dL) [30 grams per liter (g/L)]
  • You must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
  • You must be reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures
  • Patients with reproductive potential should use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drugs
  • Your test results assessing the function of your blood, kidneys, liver, and heart are satisfactory
  • You must be willing to take folic acid, Vitamin B12, or prophylactic steroids
  • You must able to interrupt the use of aspirin (other than an aspirin dose less than or equal to 1.3 grams per day) and/or other nonsteroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents, such as piroxicam)
  • You must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, hormone therapy, or other investigational therapy for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy (except alopecia). Patients who have received whole-brain radiation must wait 90 days before starting study therapy.
  • You must sign an informed consent

Exclusion Criteria:

  • You cannot have received other investigational drugs within the last 30 days
  • You cannot have other on-going serious illnesses including active bacterial, fugal, or viral infections
  • You cannot require regular, periodic paracentesis or thoracentesis
  • You cannot have active brain metastasis
  • You cannot currently be receiving warfarin (Coumadin®) therapy
  • You cannot be pregnant or lactating
  • You cannot have received prior pemetrexed or LY573636
  • You cannot have a second primary malignancy that could affect interpretation of the study results
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01215916
Other Study ID Numbers  ICMJE 11158
H8K-MC-JZAE ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP