Clinical Trials /

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

NCT02392611

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Diffuse Large B-Cell Lymphoma
  • Lymphoma
  • Malignant Solid Tumor
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: GS-US-350-1599
  • SECONDARY ID: 2016-001912-39
  • NCT ID: NCT02392611

Conditions

  • Solid Tumors
  • Lymphomas

Interventions

DrugSynonymsArms
GS-5829GS-5829 (Group 1)
ExemestaneAromasin®Combination GS-5829 (Group 2)
FulvestrantFaslodex®Combination GS-5829 (Group 2)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
GS-5829 (Group 1)ExperimentalCohorts 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.
  • GS-5829
Combination GS-5829 (Group 2)ExperimentalParticipants will receive escalating doses of GS-5829 in combination with either exemestane or fulvestrant.
  • GS-5829
  • Exemestane
  • Fulvestrant
Lymphoma Expansion (Group 3)ExperimentalParticipants 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).
  • GS-5829

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities
Time Frame:Up to 1 year
Safety Issue:
Description: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

Measure:PK profile of GS-5829: Cmax, Ctau, AUClast, AUCtau, Tmax, and t1/2
Time Frame:Predose and postdose on Days 1 and 8
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Gilead Sciences

Trial Keywords

  • Estrogen Receptor Positive Breast Cancer

Last Updated

October 18, 2017