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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 : Recruiting
First Posted : December 11, 2015
Last Update Posted : January 17, 2018
Sponsor:
Information provided by (Responsible Party):
Leap Therapeutics, Inc.

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).


Condition or disease Intervention/treatment Phase
Solid Tumors Drug: TRX518 monotherapy Drug: TRX518 with gemcitabine Drug: TRX518 with pembrolizumab Drug: TRX518 with nivolumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab in Adults With Advanced Solid Tumors
Actual Study Start Date : January 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: TRX518 monotherapy
comparison of different (ascending) doses of 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
Drug: TRX518 with gemcitabine
comparison of different (ascending) doses of TRX518 in combination 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
Drug: TRX518 with pembrolizumab
comparison of different (ascending) doses of TRX518 in combination 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
Drug: TRX518 with nivolumab
comparison of different (ascending) doses of TRX518 in combination with nivolumab




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

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): NCT02628574


Contacts
Contact: Cyndi Sirard, MD (617) 714-0357 CSirard@leaptx.com
Contact: Reena Lynam (617) 665-5206 RLynam@leaptx.com

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Jason Luke, MD       jluke@medicine.bsd.uchicago.edu   
United States, New Mexico
University of New Mexico Comprehensive Cancer Center Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Olivier Rixe, MD       ORixe@salud.unm.edu   
United States, Ohio
University Hospitals Recruiting
Cleveland, Ohio, United States, 44106
Contact: David Bajor, MD       David.Bajor@UHhospitals.org   
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Vamsidhar Velcheti, MD       velchev@ccf.org   
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Diwakar Davar, MD       davard@upmc.edu   
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37205
Contact: Todd Bauer, MD       tbauer@tnonc.com   
Contact: Erin Fisher       Erin.Fisher2@scresearch.net   
Sponsors and Collaborators
Leap Therapeutics, Inc.
Investigators
Study Chair: Cyndi Sirard, MD Leap Therapeutics, Inc.

Responsible Party: Leap Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02628574     History of Changes
Other Study ID Numbers: TRX518-003
First Posted: December 11, 2015    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Leap Therapeutics, Inc.:
Metastatic
Stage III or IV
recurrent
refractory
solid tumors

Additional relevant MeSH terms:
Gemcitabine
Pembrolizumab
Nivolumab
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs