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

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.

Condition or disease Intervention/treatment Phase
Solid Tumors Lymphomas Drug: GS-5829 Drug: Exemestane Drug: Fulvestrant Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 16, 2015
Actual Primary Completion Date : October 11, 2017
Actual Study Completion Date : October 11, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
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.
Drug: GS-5829
Tablet administered orally

Experimental: Combination GS-5829 (Group 2)
Participants will receive escalating doses of GS-5829 in combination with either exemestane or fulvestrant.
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®

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).
Drug: GS-5829
Tablet administered orally

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. 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.

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

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.

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 identifier (NCT number): NCT02392611

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United States, Arizona
Scottsdale, Arizona, United States
United States, Indiana
Fort Wayne, Indiana, United States
Goshen, Indiana, United States
United States, Texas
San Antonio, Texas, United States
Sponsors and Collaborators
Gilead Sciences
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences Identifier: NCT02392611     History of Changes
Other Study ID Numbers: GS-US-350-1599
2016-001912-39 ( EudraCT Number )
First Posted: March 19, 2015    Key Record Dates
Last Update Posted: October 20, 2017
Last Verified: October 2017

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

Keywords provided by Gilead Sciences:
Estrogen Receptor Positive Breast Cancer

Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action