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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 in Adults With Advanced Solid Tumors and Lymphomas

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: NCT02392611
Recruitment Status : Completed
First Posted : March 19, 2015
Last Update Posted : October 20, 2017
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE March 13, 2015
First Posted Date  ICMJE March 19, 2015
Last Update Posted Date October 20, 2017
Actual Study Start Date  ICMJE March 16, 2015
Actual Primary Completion Date October 11, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2015)
Incidence of dose limiting toxicities [ Time Frame: Up to 1 year ]
Dose limiting toxicity (DLT) is defined as a toxicity listed below that is considered possibly related to GS-5829 occurring during the DLT assessment window (Day 1 to 28) in each cohort:
  • Grade ≥ 4 neutropenia
  • Grade ≥ 3 neutropenia with fever
  • Grade ≥ 3 thrombocytopenia
  • Grade ≥ 2 bleeding
  • Grade ≥ 3 or higher non-hematologic toxicity (except Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical therapy and Grade 3 diarrhea which persists for < 72 hours in the absence of maximal medical therapy)
  • Grade ≥ 2 non-hematologic treatment-emergent adverse event
  • Treatment interruption of ≥ 7 days due to unresolved toxicity
  • Certain laboratory assessments without a clear clinical correlate may be assessed as a DLT (any Grade 3 or Grade 4 elevation in alanine transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to study drug will be considered a DLT)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02392611 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2015)
PK profile of GS-5829: Cmax, Ctau, AUClast, AUCtau, Tmax, and t1/2 [ Time Frame: Predose and postdose on Days 1 and 8 ]
This endpoint will measure the plasma PK profile of GS-5829. PK parameters that will be measured include Cmax, Ctau, AUClast, AUCtau, Tmax, and t1/2.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2015)
PK profile of GS-5829: Cmax, Ctau, AUClast, AUCtau, Tmax, and t½ [ Time Frame: Predose and postdose on Days 1 and 8 ]
This endpoint will measure the plasma PK profile of GS-5829. PK parameters that will be measured include Cmax, Ctau, AUClast, AUCtau, Tmax, and t½.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 in Adults With Advanced Solid Tumors and Lymphomas
Official Title  ICMJE A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 as a Monotherapy in Subjects With Advanced Solid Tumors and Lymphomas and in Combination With Exemestane or Fulvestrant in Subjects With Estrogen Receptor Positive Breast Cancer
Brief Summary This study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GS-5829 in adults with advanced solid tumors and lymphomas and in combination with exemestane or fulvestrant in adults with estrogen receptor positive breast cancer.
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
  • Lymphomas
Intervention  ICMJE
  • Drug: GS-5829
    Tablet administered orally
  • Drug: Exemestane
    Tablets administered orally once daily
    Other Name: Aromasin®
  • Drug: Fulvestrant
    Administered intramuscularly every 28 days
    Other Name: Faslodex®
Study Arms  ICMJE
  • Experimental: GS-5829 (Group 1)
    Cohorts will be sequentially enrolled at progressively higher dose levels to receive GS-5829 once daily. Participants in the first 3 cohorts will receive a single dose of GS-5829 and then approximately 7 days later, initiate dosing once daily. Each dose level will enroll 1 participant until a ≥ Grade 2 treatment-related toxicity is observed within the initial dosing period (Day 1 to Day 28). At Dose Level 5 or if a ≥ Grade 2 treatment-related toxicity is observed (whichever occurs first), the dose level will be expanded to 3 participants. Once a dosing level has expanded to 3 participants, a standard 3+3 study design will begin and dose escalation will be performed with cohort sizes of 3 to 6 participants.
    Intervention: Drug: GS-5829
  • Experimental: Combination GS-5829 (Group 2)
    Participants will receive escalating doses of GS-5829 in combination with either exemestane or fulvestrant.
    Interventions:
    • Drug: GS-5829
    • Drug: Exemestane
    • Drug: Fulvestrant
  • Experimental: Lymphoma Expansion (Group 3)
    Participants with aggressive non-hodgkin's lymphoma (NHL) may be enrolled to receive GS-5829 at a dose no higher than the maximum tolerated dose (MTD).
    Intervention: Drug: GS-5829
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: June 7, 2017)
33
Original Estimated Enrollment  ICMJE
 (submitted: March 13, 2015)
48
Actual Study Completion Date  ICMJE October 11, 2017
Actual Primary Completion Date October 11, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Group 1: Histologically or cytologically confirmed advanced malignant solid tumor or lymphoma (any subtype) that is refractory to or intolerant of standard therapy or for which no standard therapy is available
  • Group 2: Post-menopausal women with advanced stage estrogen receptor positive breast cancer who are candidates for exemestane or fulvestrant
  • Group 3: Individuals with lymphoma are limited to diffuse large B-cell lymphoma and peripheral T-cell lymphoma that are refractory to or intolerant of standard therapy or for which no standard therapy is available
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
  • Adequate organ function defined as follows:

    • Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/ dL; Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (without platelet transfusion or any growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit). Patients in the Group 3 lymphoma expansion may be enrolled with an ANC of ≥ 1.0 x 10^9 /L; Platelets ≥ 75 x 10^9 /L.
    • Hepatic: Aspartate transaminase (AST) / Alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN
    • Renal: Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 ml/min as calculated by the cockcroft-gault method
  • Coagulation: International Normalized Ratio (INR) ≤ 1.2

Key Exclusion Criteria:

  • Known brain metastasis or leptomeningeal disease
  • Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of study Day 1
  • Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (ie, larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of first dose of study drug
  • History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 450 ms for males and > 470 ms for females). Individuals who screen-fail due to this criterion are not eligible to be re-screened
  • Clinically significant bleeding within 28 days of study Day 1
  • Known human immunodeficiency virus (HIV) infection
  • HBsAG positive
  • Hepatitis C virus (HCV) antibody positive
  • No active anticoagulation within 7 days of study Day 1; including acetylsalicylic acid, low molecular weight heparin, or warfarin.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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 NCT02392611
Other Study ID Numbers  ICMJE GS-US-350-1599
2016-001912-39 ( EudraCT Number )
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 Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2017

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