Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alobresib (Formerly 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

NCT ID: NCT02392611

Last Updated: 2020-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-16
• Study Completion Date: 2017-10-11

Brief Summary

The primary objectives of this study are to characterize the safety and tolerability and determine the maximum tolerated dose (MTD) or recommended dose for phase 2 study (RDP2) of alobresib as a monotherapy in participants with advanced solid tumors and lymphomas, and in combination with exemestane or fulvestrant in participants with advanced estrogen receptor positive breast cancer.

Conditions

Solid Tumors and Lymphomas

Keywords

Estrogen Receptor Positive Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Monotherapy: Alobresib 0.6 mg

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 0.6 mg to determine the MTD.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Monotherapy: Alobresib 1.4 mg

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 1.4 mg to determine the MTD.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Monotherapy: Alobresib 2 mg

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 2 mg to determine the MTD.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Monotherapy: Alobresib 3 mg

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 3 mg to determine the MTD.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Monotherapy: Alobresib 4 mg

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 4 mg to determine the MTD.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Monotherapy: Alobresib 6 mg

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 6 mg to determine the MTD.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Combination Therapy: Alobresib 2 mg + Exemestane

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 2 mg in combination with exemestane 25 mg.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Exemestane

Intervention Type: DRUG

Tablets administered orally once daily on Cycle 1 Day 1 of 28 days cycle

Combination Therapy: Alobresib 2 mg + Fulvestrant

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 2 mg in combination with fulvestrant 500 mg.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Fulvestrant

Intervention Type: DRUG

Administered intramuscularly on Cycle 1 Day 1 of 28 days cycle and every 28 days

Combination Therapy: Alobresib 3 mg + Fulvestrant

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 3 mg in combination with fulvestrant 500 mg.

Group Type: EXPERIMENTAL

Alobresib

Intervention Type: DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Fulvestrant

Intervention Type: DRUG

Administered intramuscularly on Cycle 1 Day 1 of 28 days cycle and every 28 days

Interventions

Alobresib

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Intervention Type: DRUG

Exemestane

Tablets administered orally once daily on Cycle 1 Day 1 of 28 days cycle

Intervention Type: DRUG

Fulvestrant

Administered intramuscularly on Cycle 1 Day 1 of 28 days cycle and every 28 days

Intervention Type: DRUG

Other Intervention Names

GS-5829; Aromasin®; Faslodex®

Eligibility Criteria

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). Participants 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

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
• Hepatitis B surface antigen 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Scottsdale, Arizona, United States

Fort Wayne, Indiana, United States

Goshen, Indiana, United States

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001912-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-350-1599

Identifier Type: -

Identifier Source: org_study_id