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Phase 1 Open-label Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab

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ClinicalTrials.gov Identifier: NCT02628574
Recruitment Status : Active, not recruiting
First Posted : December 11, 2015
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Leap Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE December 1, 2015
First Posted Date  ICMJE December 11, 2015
Last Update Posted Date September 25, 2019
Actual Study Start Date  ICMJE January 2016
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
Adverse events [ Time Frame: through 30 days post last dose ]
Any adverse change in health or side effect from the initiation of the study drug dose TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab through completion or premature withdrawal
Original Primary Outcome Measures  ICMJE
 (submitted: December 9, 2015)
Adverse events [ Time Frame: through 30 days post last dose ]
Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal
Change History Complete list of historical versions of study NCT02628574 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
  • TRX518 peak concentration (Cmax) [ Time Frame: various timepoints through 1 week post dose ]
    Observations of the distribution, duration of effects and chemical changes of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab in the body and the effects and routes of the body's elimination of TRX518
  • Time to peak concentration (Tmax) [ Time Frame: various timepoints through 1 week post dose ]
    Observations of the distribution, duration of effects and chemical changes of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab in the body and the effects and routes of the body's elimination of TRX518
  • Area under the curve (AUC) [ Time Frame: various timepoints through 1 week post dose ]
    Observations of the distribution, duration of effects and chemical changes of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab in the body and the effects and routes of the body's elimination of TRX518
  • RECIST assessment for evidence of antitumor activity [ Time Frame: up to 1 year ]
    RECIST assessment to determine effects of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab on solid tumors.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2015)
  • TRX518 peak concentration (Cmax) [ Time Frame: various timepoints through 1 week post dose ]
    Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518
  • Time to peak concentration (Tmax) [ Time Frame: various timepoints through 1 week post dose ]
    Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518
  • Area under the curve (AUC) [ Time Frame: various timepoints through 1 week post dose ]
    Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518
  • RECIST assessment for evidence of antitumor activity [ Time Frame: up to 1 year ]
    RECIST assessment to determine effects of TRX518 on solid tumors.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Open-label Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab
Official Title  ICMJE A Phase 1 Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab in Adults With Advanced Solid Tumors
Brief Summary

This study will be conducted in 5 parts (Parts A, B, C, D and E).

Monotherapy Treatment:

Subjects ≥18 years with advanced solid tumors will be enrolled in the study. Monotherapy dose escalation will be performed in Part A. Cycle 1 data from each cohort will be evaluated for safety and dose-limiting toxicities (DLTs) prior to dose escalation. Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a patient is enrolled and cohorts will be dosed consecutively by ascending dose. Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been identified, an expanded cohort will be enrolled (Part B).

Combination Treatment:

Subjects ≥18 years with advanced solid tumors will be enrolled in the study. Subjects will receive TRX518 in combination with gemcitabine (Part C), pembrolizumab (Part D), or nivolumab (Part E). Dose escalation will be performed for each part (Part Cesc, Part Desc, Part Eesc) and Cycle 1 data from each cohort will be evaluated for safety and dose-limiting toxicities (DLTs) prior to dose escalation. Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a patient is enrolled and cohorts will be dosed consecutively by ascending dose. Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been identified, an expanded cohort will be enrolled (Part Cexp, Part Dexp, Part Eexp).

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: TRX518 monotherapy
    comparison of different (ascending) doses of TRX518 monotherapy
  • Drug: TRX518 with gemcitabine
    comparison of different (ascending) doses of TRX518 in combination with gemcitabine
  • Drug: TRX518 with pembrolizumab
    comparison of different (ascending) doses of TRX518 in combination with pembrolizumab
  • Drug: TRX518 with nivolumab
    comparison of different (ascending) doses of TRX518 in combination with nivolumab
Study Arms  ICMJE
  • Experimental: TRX518 monotherapy (Parts A and B)
    Subjects receive an assigned dose of TRX518 administered intravenously one time per week or one time per cycle on a 21-day cycle
    Intervention: Drug: TRX518 monotherapy
  • Experimental: TRX518 with gemcitabine (Part C)
    Subjects receive an assigned dose of TRX518 (dosed one time per cycle) intravenously administered in combination with gemcitabine (dosed two times per cycle) on a 21-day cycle
    Intervention: Drug: TRX518 with gemcitabine
  • Experimental: TRX518 with pembrolizumab (Part D
    Subjects receive an assigned dose of TRX518 (dosed one time per cycle) intravenously administered in combination with pembrolizumab (dosed one time per cycle) on a 21-day cycle
    Intervention: Drug: TRX518 with pembrolizumab
  • Experimental: TRX518 with nivolumab (Part E)
    Subjects receive an assigned dose of TRX518 (dosed two times per cycle) intravenously administered in combination with nivolumab (dosed two times per cycle) on a 28-day cycle
    Intervention: Drug: TRX518 with nivolumab
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 16, 2018)
146
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2015)
44
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Advanced Solid Malignancies: Histologically documented metastatic or locally advanced, incurable solid malignancy (Parts A and B); histologically documented metastatic or locally advanced, incurable solid malignancy for which gemcitabine is clinically appropriate (e.g., non-small cell lung, breast, ovarian, pancreatic, and renal cancer); histologically documented metastatic or locally advanced, incurable solid malignancy for which pembrolizumab (Part D) or nivolumab (Part E) is approved. NOTE: Parts D and E only: Subject has either (1) received treatment with pembrolizumab or nivolumab for ≥4 months with a best response of stable disease and plans to continue treatment with either pembrolizumab or nivolumab in accordance with package insert; or (2) is not currently taking, but is eligible for treatment with, pembrolizumab or nivolumab in accordance with the approved indications for each as referenced in the package insert.
  • Expected survival of at least 12 weeks after dosing.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Evidence of adequate organ function by standard laboratory tests.
  • All female subjects of child bearing age must be either surgically sterile, postmenopausal for at least 1 year, or using an acceptable method of contraception. Adequate contraception for both male and female subjects must be used from the beginning of the screening period until at least 8 weeks after the last dose of study drug.

Exclusion Criteria:

  • Hematologic malignancies or multiple myeloma.
  • Known, clinically important cardiac or respiratory disease
  • Any concomitant serious physical illness other than cancer (e.g., immune deficiency disease, bleeding disorder, etc.) within 1 year prior to dosing. No history of autoimmune disease.
  • Active, uncontrolled infections within 7 days of study entry requiring systemic therapy.
  • Evidence of progression of central nervous system (CNS) metastases or symptomatic CNS metastases within 30 days prior to dosing.
  • History of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment. (Parts C, D and E only).
  • Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis (Parts D and E only).
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment (Parts D and E only).
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis (Parts D and E only).
  • History of interstitial lung disease (Parts D and E only).
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 NCT02628574
Other Study ID Numbers  ICMJE TRX518-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Leap Therapeutics, Inc.
Study Sponsor  ICMJE Leap Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Cyndi Sirard, MD Leap Therapeutics, Inc.
PRS Account Leap Therapeutics, Inc.
Verification Date September 2019

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